On September 19, 2025 Johnson & Johnson (NYSE:JNJ) reported that an investigational immune-based induction regimen with TECVAYLI (teclistamab-cqyv) and DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) demonstrated meaningful clinical efficacy in transplant-eligible (TE) patients with newly diagnosed multiple myeloma (NDMM) (Press release, Johnson & Johnson, SEP 19, 2025, View Source [SID1234656115]).

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Forty-nine patients were treated across three treatment cohorts, with a steroid-sparing approach, including regimens of TECVAYLI with DARZALEX FASPRO and lenalidomide, with and without bortezomib.1 Overall response (≥partial response) was achieved by 100% of patients in all treatment arms following induction therapy.1 Of 46 MRD-evaluable patients with available samples after Cycle 3 and/or Cycle 6, 100% achieved MRD negativity by next-generation flow at 10-5 sensitivity threshold.1 By next-generation sequencing, all were MRD-negative at 10-6 after Cycle 6.1 Overall, 85.7% (42/49) of patients achieved a complete response or better (≥CR) and were MRD-negative at Cycle 6 (≤10⁻⁵).1 Additionally, 96% of patients successfully completed stem cell mobilization with a median total stem cell yield of 8.1×106/kg.1

"Multiple myeloma weakens the immune system over time, making it difficult to eliminate cancerous plasma cells," said Marc S. Raab, M.D., Heidelberg University Hospital, Germany.* "It’s critical to treat patients with the most effective regimens in the newly diagnosed setting. TECVAYLI and DARZALEX FASPRO work synergistically to significantly reduce cancer cells – resulting in deep responses with potential for long term benefit."

Data from the safety analysis reinforced the tolerability of the approach.1 The most common treatment-emergent adverse events (TEAEs) were hematologic, and Grade 3/4 infections occurred in 36.7% of patients.1 Serious TEAEs occurred in 53% (n=26) of patients.1 No TEAEs led to full study treatment discontinuation and no Grade 5 adverse events were observed.1 Additionally, no patients experienced immune effector cell-associated neurotoxicity syndrome (ICANS).1 Cytokine release syndrome (CRS) was observed in 65% of patients (n=32) and were all Grade 1/2.1

"Exploring TECVAYLI, with its established use in later lines of treatment, and DARZALEX FASPRO, a foundational therapy across all lines, together helps us understand how this doublet immunotherapy can support patients across different stages of disease," said Jordan Schecter, M.D., Vice President, Disease Area Leader, Multiple Myeloma, Johnson & Johnson Innovative Medicine. "Importantly, immune-based therapies like TECVAYLI have the potential to improve patient outcomes with a manageable safety profile, particularly when used earlier in the treatment journey, with 100 percent of evaluable patients achieving MRD negativity. We continue to explore TECVAYLI in earlier lines of therapy and across difficult-to-treat populations."

About MajesTEC-5 Study
MajesTEC-5 (NCT05695508) is an ongoing, Phase 2 study evaluating the safety and efficacy of combination regimens including teclistamab and daratumumab in participants with newly diagnosed transplant eligible multiple myeloma. The MajesTEC-5 clinical trial is sponsored by the German-Speaking Myeloma Multicenter Group (GMMG) and Deutsche Studiengruppe Multiples Myelom (DSMM), and conducted in collaboration with Johnson & Johnson.2

About TECVAYLI
TECVAYLI (teclistamab-cqyv) received approval from the U.S. FDA in October 2022 as an off-the-shelf (or ready-to-use) antibody that is administered as a subcutaneous treatment for adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody.3 Since FDA approval, more than 15,900 patients have been treated worldwide with TECVAYLI. The European Commission (EC) granted TECVAYLI conditional marketing authorization (CMA) in August 2022 as monotherapy for the treatment of adult patients with RRMM who have received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody, and have demonstrated disease progression since the last therapy. In August 2023, the EC granted the approval of a Type II variation application for TECVAYLI, providing the option for a reduced dosing frequency of 1.5 mg/kg every two weeks (Q2W) in patients who have achieved a complete response (CR) or better for a minimum of six months. TECVAYLI is a first-in-class, bispecific T-cell engager antibody therapy that uses innovative science to activate the immune system by binding to the CD3 receptor expressed on the surface of T-cells and to the B-cell maturation antigen (BCMA) expressed on the surface of multiple myeloma cells and some healthy B-lineage cells. In February 2024, the U.S. FDA approved the supplemental Biologics License Application (sBLA) for TECVAYLI for a reduced dosing frequency of 1.5 mg/kg every two weeks in patients with relapsed or refractory multiple myeloma who have achieved and maintained a CR or better for a minimum of six months.

For more information, visit www.TECVAYLI.com.

About DARZALEX FASPRO and DARZALEX
DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) received U.S. FDA approval in May 2020 and is approved for ten indications in multiple myeloma, three of which are for frontline treatment in newly diagnosed patients who are transplant eligible or ineligible. It is the only subcutaneous CD38-directed antibody approved to treat patients with MM. DARZALEX FASPRO is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE drug delivery technology.

DARZALEX (daratumumab) received U.S. FDA approval in November 2015 and is approved in ten indications, three of which are in the frontline setting, including newly diagnosed patients who are transplant eligible and ineligible.

DARZALEX is the first CD38-directed antibody approved to treat multiple myeloma. DARZALEX-based regimens have been used in the treatment of more than 618,000 patients worldwide.

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize daratumumab.

Since 2020, the National Comprehensive Cancer Network (NCCN) has recommended daratumumab-based combination regimens for the treatment of newly diagnosed multiple myeloma and relapsed and refractory multiple myeloma.† For newly diagnosed multiple myeloma in non-transplant candidates, the NCCN guidelines recommend daratumumab in combination with lenalidomide and dexamethasone as a Category 1 preferred regimen; daratumumab in combination with bortezomib, melphalan, and prednisone as another recommended Category 1 regimen; and daratumumab in combination with bortezomib, cyclophosphamide, and prednisone as another recommended Category 2A regimen. For newly diagnosed multiple myeloma in transplant candidates, the NCCN guidelines recommend daratumumab in combination with bortezomib, lenalidomide and dexamethasone as another recommended Category 2A regimen; daratumumab in combination with bortezomib, thalidomide and dexamethasone as a Category 2A regimen useful in certain circumstances; daratumumab in combination with carfilzomib, lenalidomide and dexamethasone as a Category 2A regimen useful in certain circumstances; and daratumumab in combination with cyclophosphamide, bortezomib and dexamethasone as a Category 2A regimen useful in certain circumstances. For maintenance in transplant candidates, the NCCN guidelines recommend daratumumab in combination with lenalidomide as useful in certain circumstances. In relapsed/refractory myeloma, four daratumumab regimens are listed as Category 1 preferred regimens for early relapses (1-3 prior therapies): daratumumab in combination with lenalidomide and dexamethasone; daratumumab in combination with bortezomib and dexamethasone; daratumumab in combination with carfilzomib and dexamethasone; and daratumumab in combination with pomalidomide and dexamethasone [after one prior therapy including lenalidomide and a proteasome inhibitor (PI)]. The NCCN also recommends daratumumab in combination with cyclophosphamide, bortezomib and dexamethasone as another Category 2A regimen for early relapses (1-3 prior therapies) and as monotherapy as a Category 2A regimen useful in certain circumstances for early relapse patients after at least three prior therapies, including a PI and an immunomodulatory agent, or for patients who are double refractory to a PI and an immunomodulatory agent.

For more information, visit www.DARZALEX.com.

About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.4 In multiple myeloma, these plasma cells proliferate and spread rapidly and replace normal cells in the bone marrow with tumors.5 Multiple myeloma is the third most common blood cancer worldwide and remains an incurable disease.6 In 2024, it was estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 people would die from the disease.7 People living with multiple myeloma have a 5-year survival rate of 59.8 percent.8 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels and kidney problems or infections.9,10

TECVAYLI IMPORTANT SAFETY INFORMATION

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME

Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving TECVAYLI. Initiate treatment with TECVAYLI step-up dosing schedule to reduce risk of CRS. Withhold TECVAYLI until CRS resolves or permanently discontinue based on severity.

Neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) and serious and life-threatening reactions, can occur in patients receiving TECVAYLI. Monitor patients for signs or symptoms of neurologic toxicity, including ICANS, during treatment. Withhold TECVAYLI until neurologic toxicity resolves or permanently discontinue based on severity.

TECVAYLI is available only through a restricted program called the TECVAYLI and TALVEY Risk Evaluation and Mitigation Strategy (REMS).

INDICATION AND USAGE

TECVAYLI (teclistamab-cqyv) is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody.

This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

WARNINGS AND PRECAUTIONS

Cytokine Release Syndrome – TECVAYLI can cause cytokine release syndrome (CRS), including life-threatening or fatal reactions. In the clinical trial, CRS occurred in 72% of patients who received TECVAYLI at the recommended dose, with Grade 1 CRS occurring in 50% of patients, Grade 2 in 21%, and Grade 3 in 0.6%. Recurrent CRS occurred in 33% of patients. Most patients experienced CRS following step-up dose 1 (42%), step-up dose 2 (35%), or the initial treatment dose (24%). Less than 3% of patients developed first occurrence of CRS following subsequent doses of TECVAYLI. The median time to onset of CRS was 2 (range: 1 to 6) days after the most recent dose with a median duration of 2 (range: 1 to 9) days. Clinical signs and symptoms of CRS included, but were not limited to, fever, hypoxia, chills, hypotension, sinus tachycardia, headache, and elevated liver enzymes (aspartate aminotransferase and alanine aminotransferase elevation).

Initiate therapy according to TECVAYLI step-up dosing schedule to reduce risk of CRS. Administer pretreatment medications to reduce risk of CRS and monitor patients following administration of TECVAYLI accordingly. At the first sign of CRS, immediately evaluate patient for hospitalization. Administer supportive care based on severity and consider further management per current practice guidelines. Withhold or permanently discontinue TECVAYLI based on severity.

TECVAYLI is available only through a restricted program under a REMS.

Neurologic Toxicity including ICANS – TECVAYLI can cause serious or life-threatening neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS).

In the clinical trial, neurologic toxicity occurred in 57% of patients who received TECVAYLI at the recommended dose, with Grade 3 or 4 neurologic toxicity occurring in 2.4% of patients. The most frequent neurologic toxicities were headache (25%), motor dysfunction (16%), sensory neuropathy (15%), and encephalopathy (13%). With longer follow-up, Grade 4 seizure and fatal Guillain-Barré syndrome (one patient each) occurred in patients who received TECVAYLI.

In the clinical trial, ICANS was reported in 6% of patients who received TECVAYLI at the recommended dose. Recurrent ICANS occurred in 1.8% of patients. Most patients experienced ICANS following step-up dose 1 (1.2%), step-up dose 2 (0.6%), or the initial treatment dose (1.8%). Less than 3% of patients developed first occurrence of ICANS following subsequent doses of TECVAYLI. The median time to onset of ICANS was 4 (range: 2 to 8) days after the most recent dose with a median duration of 3 (range: 1 to 20) days. The most frequent clinical manifestations of ICANS reported were confusional state and dysgraphia. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS.

Monitor patients for signs and symptoms of neurologic toxicity during treatment. At the first sign of neurologic toxicity, including ICANS, immediately evaluate patient and provide supportive therapy based on severity. Withhold or permanently discontinue TECVAYLI based on severity per recommendations and consider further management per current practice guidelines.

Due to the potential for neurologic toxicity, patients are at risk of depressed level of consciousness. Advise patients to refrain from driving or operating heavy or potentially dangerous machinery during and for 48 hours after completion of TECVAYLI step-up dosing schedule and in the event of new onset of any neurologic toxicity symptoms until neurologic toxicity resolves.

TECVAYLI is available only through a restricted program under a REMS.

TECVAYLI and TALVEY REMS – TECVAYLI is available only through a restricted program under a REMS called the TECVAYLI and TALVEY REMS because of the risks of CRS and neurologic toxicity, including ICANS.

Hepatotoxicity – TECVAYLI can cause hepatotoxicity, including fatalities. In patients who received TECVAYLI at the recommended dose in the clinical trial, there was one fatal case of hepatic failure. Elevated aspartate aminotransferase (AST) occurred in 34% of patients, with Grade 3 or 4 elevations in 1.2%. Elevated alanine aminotransferase (ALT) occurred in 28% of patients, with Grade 3 or 4 elevations in 1.8%. Elevated total bilirubin occurred in 6% of patients with Grade 3 or 4 elevations in 0.6%. Liver enzyme elevation can occur with or without concurrent CRS.

Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity.

Infections – TECVAYLI can cause severe, life-threatening, or fatal infections. In patients who received TECVAYLI at the recommended dose in the clinical trial, serious infections, including opportunistic infections, occurred in 30% of patients, with Grade 3 or 4 infections in 35%, and fatal infections in 4.2%.

Monitor patients for signs and symptoms of infection prior to and during treatment with TECVAYLI and treat appropriately. Administer prophylactic antimicrobials according to guidelines. Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity.

Monitor immunoglobulin levels during treatment with TECVAYLI and treat according to guidelines, including infection precautions and antibiotic or antiviral prophylaxis.

Neutropenia – TECVAYLI can cause neutropenia and febrile neutropenia. In patients who received TECVAYLI at the recommended dose in the clinical trial, decreased neutrophils occurred in 84% of patients, with Grade 3 or 4 decreased neutrophils in 56%. Febrile neutropenia occurred in 3% of patients.

Monitor complete blood cell counts at baseline and periodically during treatment and provide supportive care per local institutional guidelines. Monitor patients with neutropenia for signs of infection. Withhold TECVAYLI based on severity.

Hypersensitivity and Other Administration Reactions – TECVAYLI can cause both systemic administration-related and local injection-site reactions. Systemic Reactions – In patients who received TECVAYLI at the recommended dose in the clinical trial, 1.2% of patients experienced systemic-administration reactions, which included Grade 1 recurrent pyrexia and Grade 1 swollen tongue. Local Reactions – In patients who received TECVAYLI at the recommended dose in the clinical trial, injection-site reactions occurred in 35% of patients, with Grade 1 injection-site reactions in 30% and Grade 2 in 4.8%. Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity.

Embryo-Fetal Toxicity – Based on its mechanism of action, TECVAYLI may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with TECVAYLI and for 5 months after the last dose.

ADVERSE REACTIONS

The most common adverse reactions (≥20%) were pyrexia, CRS, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea. The most common Grade 3 to 4 laboratory abnormalities (≥20%) were decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, and decreased platelets.

Please read full Prescribing Information, including Boxed WARNING, for TECVAYLI.

DARZALEX INDICATIONS AND IMPORTANT SAFETY INFORMATION

INDICATIONS
DARZALEX (daratumumab) is indicated for the treatment of adult patients with multiple myeloma:

In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy
In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant
In combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor
In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
As monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent
CONTRAINDICATIONS

DARZALEX is contraindicated in patients with a history of severe hypersensitivity (eg, anaphylactic reactions) to daratumumab or any of the components of the formulation.

WARNINGS AND PRECAUTIONS

Infusion-Related Reactions

DARZALEX can cause severe and/or serious infusion-related reactions including anaphylactic reactions. These reactions can be life threatening, and fatal outcomes have been reported. In clinical trials (monotherapy and combination: N=2066), infusion-related reactions occurred in 37% of patients with the Week 1 (16 mg/kg) infusion, 2% with the Week 2 infusion, and cumulatively 6% with subsequent infusions. Less than 1% of patients had a Grade 3/4 infusion-related reaction at Week 2 or subsequent infusions. The median time to onset was 1.5 hours (range: 0 to 73 hours). Nearly all reactions occurred during infusion or within 4 hours of completing DARZALEX. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension and blurred vision.

When DARZALEX dosing was interrupted in the setting of ASCT (CASSIOPEIA) for a median of 3.75 months (range: 2.4 to 6.9 months), upon re-initiation of DARZALEX, the incidence of infusion-related reactions was 11% for the first infusion following ASCT. Infusion-related reactions occurring at re-initiation of DARZALEX following ASCT were consistent in terms of symptoms and severity (Grade 3 or 4: <1%) with those reported in previous studies at Week 2 or subsequent infusions. In EQUULEUS, patients receiving combination treatment (n=97) were administered the first 16 mg/kg dose at Week 1 split over two days, ie, 8 mg/kg on Day 1 and Day 2, respectively. The incidence of any grade infusion-related reactions was 42%, with 36% of patients experiencing infusion-related reactions on Day 1 of Week 1, 4% on Day 2 of Week 1, and 8% with subsequent infusions.

Pre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt DARZALEX infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX therapy if an anaphylactic reaction or life-threatening (Grade 4) reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.

To reduce the risk of delayed infusion-related reactions, administer oral corticosteroids to all patients following DARZALEX infusions. Patients with a history of chronic obstructive pulmonary disease may require additional post-infusion medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with chronic obstructive pulmonary disease.

Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with DARZALEX infusion. If ocular symptoms occur, interrupt DARZALEX infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX.

Interference With Serological Testing

Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab infusion. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type is not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX. Type and screen patients prior to starting DARZALEX.

Neutropenia and Thrombocytopenia

DARZALEX may increase neutropenia and thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX until recovery of neutrophils or for recovery of platelets.

Interference With Determination of Complete Response

Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.

Embryo-Fetal Toxicity

Based on the mechanism of action, DARZALEX can cause fetal harm when administered to a pregnant woman. DARZALEX may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX and for 3 months after the last dose.

The combination of DARZALEX with lenalidomide, pomalidomide, or thalidomide is contraindicated in pregnant women because lenalidomide, pomalidomide, and thalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, pomalidomide, or thalidomide prescribing information on use during pregnancy.

ADVERSE REACTIONS

The most frequently reported adverse reactions (incidence ≥20%) were: upper respiratory infection, neutropenia, infusion related reactions, thrombocytopenia, diarrhea, constipation, anemia, peripheral sensory neuropathy, fatigue, peripheral edema, nausea, cough, pyrexia, dyspnea, and asthenia. The most common hematologic laboratory abnormalities (≥40%) with DARZALEX are: neutropenia, lymphopenia, thrombocytopenia, leukopenia, and anemia.

Please click here to see the full Prescribing Information.

On September 19, 2025 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted two positive opinions for KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy (Press release, Merck & Co, SEP 19, 2025, View Source [SID1234656104]). One recommends approval of a new subcutaneous (SC) route of administration and a new pharmaceutical form (solution for injection) for KEYTRUDA (pembrolizumab), which if approved would be marketed in the European Union (EU) as KEYTRUDA SC. The other positive opinion recommends approval of a new indication in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). The CHMP recommendations will now be reviewed by the European Commission (EC) for marketing authorization in the EU, Iceland, Liechtenstein and Norway, and final decisions are expected in the fourth quarter of 2025.

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"Building on the legacy of KEYTRUDA, we are committed to driving innovation in cancer care with new routes of administration and indications in difficult-to-treat and earlier stages of cancer," said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. "This is a significant step forward in our pursuit of bringing this therapy to more patients. If approved, we believe KEYTRUDA SC has the potential to provide meaningful benefits to patients and providers in Europe because it can offer a shorter administration time compared to KEYTRUDA and the option to receive treatment in additional health care settings."

The first CHMP opinion recommends approval of KEYTRUDA SC as a subcutaneous, or under the skin, injection administered by a health care provider. If approved, KEYTRUDA SC could be administered in one minute every three weeks (395 mg) or in two minutes every six weeks (790 mg). As a subcutaneous injection, a health care provider would be able to administer KEYTRUDA SC in multiple settings, providing more options where patients can receive their treatment. The CHMP’s positive opinion applies to all KEYTRUDA indications for adult patients in Europe. KEYTRUDA SC contains pembrolizumab and berahyaluronidase alfa, a variant of human hyaluronidase, developed and manufactured by Alteogen Inc.

The marketing authorization application for KEYTRUDA SC is based on results from the pivotal 3475A-D77 trial comparing KEYTRUDA SC and KEYTRUDA administered every six weeks, each with chemotherapy, studied in patients with treatment naïve metastatic non-small cell lung cancer (NSCLC) with no EGFR, ALK or ROS1 genomic tumor aberrations. This trial demonstrated comparable pharmacokinetic exposure levels between KEYTRUDA SC and KEYTRUDA. The secondary efficacy endpoints of objective response rate (ORR) and progression-free survival (PFS), which were descriptive analyses, were consistent for KEYTRUDA SC with chemotherapy compared to KEYTRUDA with chemotherapy. The ORR in the KEYTRUDA SC with chemotherapy arm was 45.4% (95% CI, 39.1-51.8) and 42.1% (95% CI, 33.3-51.2) in the KEYTRUDA with chemotherapy arm.

Results from the trial were presented at the European Lung Cancer Congress (ELCC) 2025 in March and published simultaneously in Annals of Oncology. A Biologics License Application (BLA) seeking approval of subcutaneous pembrolizumab for use in adults across all previously approved solid tumor indications for KEYTRUDA is currently under review in the U.S. with a Prescription Drug User Fee Act (PDUFA), or target action, date of Sept. 23, 2025.

The second CHMP opinion recommends approval of KEYTRUDA as monotherapy for the treatment of resectable locally advanced head and neck squamous cell carcinoma (LA-HNSCC) as neoadjuvant treatment, continued as adjuvant treatment in combination with radiation therapy with or without concomitant cisplatin and then as monotherapy in adults whose tumors express PD-L1 with a Combined Positive Score (CPS) ≥1. This treatment regimen would be the first perioperative anti-PD-1 treatment option for certain patients with resectable LA-HNSCC in the EU.

The recommendation for resectable LA-HNSCC is based on results from the pivotal Phase 3 KEYNOTE-689 trial. At the trial’s first pre-specified interim analysis, the KEYTRUDA-based perioperative regimen demonstrated a statistically significant and clinically meaningful improvement in event-free survival (EFS), the study’s primary endpoint, compared to adjuvant radiotherapy (RT) (with or without cisplatin) alone in patients with tumors expressing PD-L1 (CPS >1). Results from the trial were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in April 2025 and also published in The New England Journal of Medicine in June 2025. In June 2025, KEYTRUDA was approved in the U.S. for the treatment of adult patients with resectable LA-HNSCC whose tumors express PD-L1 (CPS ≥1) as determined by a Food and Drug Administration (FDA)-approved test, as a single agent as neoadjuvant treatment, continued as adjuvant treatment in combination with RT with or without cisplatin and then as a single agent.

About Subcutaneous Administration
Subcutaneous administration is a method of delivering medications under the skin. As an alternative to intravenous infusion, subcutaneous administration potentially offers more options where patients can receive their treatment because it can be administered by healthcare providers in multiple settings from an infusion center to a doctor’s office or a local community-based clinic. For patients who do not require a port or whose veins are difficult to access, subcutaneous administration may simplify treatment administration.

About head and neck cancer
Head and neck cancer describes a number of different tumors that develop in or around the throat, larynx, nose, sinuses and mouth. It is estimated there were more than 947,200 new cases of head and neck cancer diagnosed and more than 482,400 deaths from the disease in 2022 globally. In Europe, it is estimated there were approximately 161,900 new cases of head and neck cancer and more than 72,500 deaths from the disease in 2022. These data include cancers of the oral cavity, pharynx and larynx. Most head and neck cancers are squamous cell carcinomas, which begin in the flat, squamous cells that make up the thin mucosal lining of the head and neck. Locally advanced head and neck squamous cell carcinoma is cancer that has spread from where it started to nearby tissue or lymph nodes but has not yet spread to distant parts of the body. There are several factors that greatly increase the risk of developing head and neck cancer, including tobacco and alcohol use and human papillomavirus.

On September 19, 2025 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that the U.S. Food and Drug Administration (FDA) has approved KEYTRUDA QLEX (pembrolizumab and berahyaluronidase alfa-pmph) injection for subcutaneous administration in adults across most solid tumor indications for KEYTRUDA (pembrolizumab) (Press release, Merck & Co, SEP 19, 2025, View Source [SID1234656103]). Berahyaluronidase alfa is a variant of human hyaluronidase developed and manufactured by Alteogen Inc. KEYTRUDA QLEX must be administered by a health care provider (HCP). Merck expects to have KEYTRUDA QLEX (pronounced key-TRUE-duh Q-lex) available in the U.S. in late September. For a full list of the 38 indications for which KEYTRUDA QLEX is approved, see "KEYTRUDA QLEX Indications" below.

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"This approval is significant for patients and health care providers like me who have been using immunotherapies for years to treat certain cancers. We now have a new option with a broad set of indications that has demonstrated comparability with intravenous (IV) pembrolizumab but in a subcutaneous injection that can be administered in one minute every three weeks or two minutes every six weeks," said Dr. J. Thaddeus Beck, oncologist and Medical Director of the Highlands’ Clinical Trials Office. "Subcutaneous pembrolizumab provides faster administration than IV pembrolizumab, offers two dosing options and gives patients more choices of health care settings in which they can receive their therapy."

The pivotal trial comparing subcutaneous KEYTRUDA QLEX to IV KEYTRUDA administered every six weeks, each with chemotherapy, was conducted in patients with treatment-naïve metastatic non-small cell lung cancer (NSCLC) with no EGFR, ALK or ROS1 genomic tumor aberrations. This trial demonstrated comparable pharmacokinetic exposure levels to pembrolizumab [assessed as Cycle 1 AUC0-6 weeks (area under the curve from 0 to 6 weeks) and Cycle 3 (i.e. Steady State) Ctrough]. In descriptive efficacy analyses, overall response rates (ORR) were similar between KEYTRUDA QLEX and KEYTRUDA (45% [95% CI: 39, 52] vs 42% [95% CI: 33, 51]). Additionally, no notable differences were observed in progression-free survival (PFS) and overall survival (OS). Effectiveness of KEYTRUDA QLEX for its approved indications was established based on these data and pivotal trial data demonstrating comparable safety with KEYTRUDA, as well as evidence from adequate and well-controlled studies conducted with KEYTRUDA.

KEYTRUDA QLEX is contraindicated in patients with known hypersensitivity to berahyaluronidase alfa, hyaluronidase or to any of its excipients. Additionally, immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue and can affect more than one body system simultaneously. Immune-mediated adverse reactions can occur at any time after starting treatment with a PD-1/PD-L1 blocking antibody, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection and other transplant (including corneal graft) rejection. Additionally, fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after treatment. Consider the benefit versus risks for these patients. Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled trials due to the potential for increased mortality. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of KEYTRUDA QLEX. Based on the severity of the adverse reaction, KEYTRUDA QLEX should be withheld or permanently discontinued and corticosteroids administered if appropriate. KEYTRUDA QLEX can also cause severe or life-threatening administration-related reactions. Based on its mechanism of action, KEYTRUDA QLEX can cause fetal harm when administered to a pregnant woman. For more information, see "Selected Important Safety Information" below.

As a subcutaneous injection, KEYTRUDA QLEX may provide added convenience compared to IV KEYTRUDA because it can be administered by HCPs in multiple settings from an infusion center to a doctor’s office or a local community-based clinic, providing more options where patients can receive their treatment. KEYTRUDA QLEX also provides flexibility in treatment administration. It can be given in one minute every three weeks or in two minutes every six weeks, requiring substantially less time to administer than a 30-minute IV infusion of KEYTRUDA, and also offers a choice of injection site in the thigh or abdomen avoiding the 5 cm area around the navel. For patients who do not require a port or whose veins are difficult to access, subcutaneous administration may simplify treatment administration.

"At Merck, we are committed to putting patients first, as we work relentlessly to discover new options that may help patients manage their treatment in a way that fits their needs," said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. "We are honored to build on the foundation of KEYTRUDA with KEYTRUDA QLEX, a new injectable immunotherapy option that has similar results to KEYTRUDA and can be administered in as little as one minute."

"As part of supporting patients and families through their cancer journeys, we are excited to see patient-focused developments in subcutaneous cancer treatment that shorten administration time and may allow for more patients to receive treatment in multiple health care settings," said Sally Werner, Chief Executive Officer, Cancer Support Community.

Study 3475A-D77 trial design and additional data supporting the approval

Study 3475A-D77 is a multicenter, randomized, open-label, active-controlled Phase 3 trial (ClinicalTrials.gov, NCT05722015) conducted in patients with treatment-naïve metastatic non-small cell lung cancer (NSCLC) with no EGFR, ALK or ROS1 genomic tumor aberrations. The primary outcome measure was pembrolizumab exposure [Cycle 1 AUC0-6 weeks and Cycle 3 (i.e. Steady State) Ctrough] of subcutaneous KEYTRUDA QLEX as compared to IV pembrolizumab. Additional descriptive efficacy outcome measures were ORR by blinded independent central review (BICR), PFS by BICR and OS.

A total of 377 patients were randomized 2:1 to receive either KEYTRUDA QLEX (790 mg/9,600 units) every six weeks with platinum doublet chemotherapy (n=251) or pembrolizumab (400 mg) every six weeks with platinum doublet chemotherapy (n=126).

At the primary analysis, the confirmed ORR was 45% (95% Cl: 39, 52) in the subcutaneous KEYTRUDA QLEX arm versus 42% (95% Cl: 33, 51) for IV pembrolizumab arm. There were no notable differences in PFS and OS observed in patients who received KEYTRUDA QLEX compared to patients who received IV pembrolizumab.

The most common adverse reactions (≥20%) of patients who received KEYTRUDA QLEX in combination with chemotherapy were nausea (25%), fatigue (25%), and musculoskeletal pain (21%).

About KEYTRUDA QLEX (pembrolizumab and berahyaluronidase alfa-pmph) injection for subcutaneous use

KEYTRUDA QLEX is a fixed-combination drug product of pembrolizumab and berahyaluronidase alfa. Pembrolizumab is a programmed death receptor-1 (PD-1) blocking antibody and berahyaluronidase alfa enhances dispersion and permeability to enable subcutaneous administration of pembrolizumab. KEYTRUDA QLEX is administered as a subcutaneous injection into the thigh or abdomen, avoiding the 5 cm area around the navel, over one minute every three weeks (2.4 mL) or over two minutes every six weeks (4.8 mL).

Selected KEYTRUDA QLEX (pembrolizumab and berahyaluronidase alfa-pmph) Indications

Melanoma

KEYTRUDA QLEX is indicated for the treatment of adult patients with unresectable or metastatic melanoma.

KEYTRUDA QLEX is indicated for the adjuvant treatment of adult and pediatric patients 12 years and older with Stage IIB, IIC, or III melanoma following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA QLEX, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of adult patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA QLEX, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of adult patients with metastatic squamous NSCLC.

KEYTRUDA QLEX, as a single agent, is indicated for the first-line treatment of adult patients with NSCLC expressing PD-L1 [Tumor Proportion Score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:

Stage III where patients are not candidates for surgical resection or definitive chemoradiation, or
metastatic.
KEYTRUDA QLEX, as a single agent, is indicated for the treatment of adult patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA QLEX.

KEYTRUDA QLEX is indicated for the treatment of adult patients with resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.

KEYTRUDA QLEX, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC.

Malignant Pleural Mesothelioma

KEYTRUDA QLEX, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic malignant pleural mesothelioma (MPM).

Head and Neck Squamous Cell Cancer

KEYTRUDA QLEX, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of adult patients with metastatic or with unresectable, recurrent HNSCC.

KEYTRUDA QLEX, as a single agent, is indicated for the first-line treatment of adult patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test.

KEYTRUDA QLEX, as a single agent, is indicated for the treatment of adult patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.

Urothelial Cancer

KEYTRUDA QLEX, in combination with enfortumab vedotin, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer.

KEYTRUDA QLEX, as a single agent, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma:

who are not eligible for any platinum-containing chemotherapy, or
who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
KEYTRUDA QLEX, as a single agent, is indicated for the treatment of adult patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High or Mismatch Repair Deficient Cancer

KEYTRUDA QLEX is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

KEYTRUDA QLEX is indicated for the treatment of adult patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC) as determined by an FDA-approved test.

Gastric Cancer

KEYTRUDA QLEX, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.

KEYTRUDA QLEX, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Esophageal Cancer

KEYTRUDA QLEX is indicated for the treatment of adult patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:

in combination with platinum- and fluoropyrimidine-based chemotherapy, or
as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
Cervical Cancer

KEYTRUDA QLEX, in combination with chemoradiotherapy (CRT), is indicated for the treatment of adult patients with FIGO 2014 Stage III-IVA cervical cancer.

KEYTRUDA QLEX, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of adult patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.

KEYTRUDA QLEX, as a single agent, is indicated for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.

Hepatocellular Carcinoma

KEYTRUDA QLEX is indicated for the treatment of adult patients with hepatocellular carcinoma (HCC) secondary to hepatitis B who have received prior systemic therapy other than a PD-1/PD-L1-containing regimen.

Biliary Tract Cancer

KEYTRUDA QLEX, in combination with gemcitabine and cisplatin, is indicated for the treatment of adult patients with locally advanced unresectable or metastatic biliary tract cancer (BTC).

Merkel Cell Carcinoma

KEYTRUDA QLEX is indicated for the treatment of adult and pediatric patients 12 years and older with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC).

Renal Cell Carcinoma

KEYTRUDA QLEX, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).

KEYTRUDA QLEX is indicated for the adjuvant treatment of adult patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.

Endometrial Carcinoma

KEYTRUDA QLEX, in combination with carboplatin and paclitaxel, followed by KEYTRUDA QLEX as a single agent, is indicated for the treatment of adult patients with primary advanced or recurrent endometrial carcinoma.

KEYTRUDA QLEX, as a single agent, is indicated for the treatment of adult patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.

Cutaneous Squamous Cell Carcinoma

KEYTRUDA QLEX is indicated for the treatment of adult patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.

Triple-Negative Breast Cancer

KEYTRUDA QLEX is indicated for the treatment of adult patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.

KEYTRUDA QLEX, in combination with chemotherapy, is indicated for the treatment of adult patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.

Selected Important Safety Information for KEYTRUDA QLEX

Contraindications

KEYTRUDA QLEX is contraindicated in patients with known hypersensitivity to berahyaluronidase alfa, hyaluronidase or to any of its excipients.

Severe and Fatal Immune-Mediated Adverse Reactions

KEYTRUDA QLEX is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or the programmed death ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.

Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of anti–PD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. For patients with TNBC treated with KEYTRUDA QLEX in the neoadjuvant setting, monitor blood cortisol at baseline, prior to surgery, and as clinically indicated. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue KEYTRUDA QLEX depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA QLEX requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

KEYTRUDA QLEX can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 5% (13/251) of patients receiving KEYTRUDA QLEX in combination with chemotherapy, including fatal (0.4%), Grade 3 (2%), and Grade 2 (1.2%) adverse reactions.

Intravenous Pembrolizumab as a Single Agent

Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving intravenous pembrolizumab, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of intravenous pembrolizumab in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated intravenous pembrolizumab after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.

Pneumonitis occurred in 7% (41/580) of adult patients with resected NSCLC who received intravenous pembrolizumab as a single agent for adjuvant treatment of NSCLC, including fatal (0.2%), Grade 4 (0.3%), and Grade 3 (1%) adverse reactions. Patients received high-dose corticosteroids for a median duration of 10 days (range: 1 day to 2.3 months). Pneumonitis led to discontinuation of intravenous pembrolizumab in 26 (4.5%) of patients. Of the patients who developed pneumonitis, 54% interrupted intravenous pembrolizumab, 63% discontinued intravenous pembrolizumab, and 71% had resolution.

Immune-Mediated Colitis

KEYTRUDA QLEX can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.2% (3/251) of patients receiving KEYTRUDA QLEX in combination with chemotherapy, including Grade 3 (0.8%) and Grade 2 (0.4%) adverse reactions.

Intravenous Pembrolizumab as a Single Agent

Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving intravenous pembrolizumab, including Grade 4 (<0.1%), Grade 3 (1.1%), and Grade 2 (0.4%) reactions. Systemic corticosteroids were required in 69% (33/48); additional immunosuppressant therapy was required in 4.2% of patients. Colitis led to permanent discontinuation of intravenous pembrolizumab in 0.5% (15) and withholding in 0.5% (13) of patients. All patients who were withheld reinitiated intravenous pembrolizumab after symptom improvement; of these, 23% had recurrence. Colitis resolved in 85% of the 48 patients.

Hepatotoxicity and Immune-Mediated Hepatitis

KEYTRUDA QLEX as a Single Agent

KEYTRUDA QLEX can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 0.4% (1/251) of patients receiving KEYTRUDA QLEX in combination with chemotherapy, including Grade 2 (0.4%) adverse reactions.

Intravenous Pembrolizumab as a Single Agent

Immune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving intravenous pembrolizumab, including Grade 4 (<0.1%), Grade 3 (0.4%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 68% (13/19) of patients; additional immunosuppressant therapy was required in 11% of patients. Hepatitis led to permanent discontinuation of intravenous pembrolizumab in 0.2% (6) and withholding in 0.3% (9) of patients. All patients who were withheld reinitiated intravenous pembrolizumab after symptom improvement; of these, none had recurrence. Hepatitis resolved in 79% of the 19 patients.

KEYTRUDA QLEX With Axitinib

KEYTRUDA QLEX in combination with axitinib can cause hepatic toxicity. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider monitoring more frequently as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA QLEX and axitinib, and consider administering corticosteroids as needed.

With the combination of intravenous pembrolizumab and axitinib, Grades 3 and 4 increased alanine aminotransferase (ALT) (20%) and increased aspartate aminotransferase (AST) (13%) were seen at a higher frequency compared to intravenous pembrolizumab alone. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. In patients with ALT ≥3 times upper limit of normal (ULN) (Grades 2-4, n=116), ALT resolved to Grades 0-1 in 94%. Among the 92 patients who were rechallenged with either intravenous pembrolizumab (n=3) or axitinib (n=34) administered as a single agent or with both (n=55), recurrence of ALT ≥3 times ULN was observed in 1 patient receiving intravenous pembrolizumab, 16 patients receiving axitinib, and 24 patients receiving both. All patients with a recurrence of ALT ≥3 ULN subsequently recovered from the event.

Immune-Mediated Endocrinopathies

Adrenal Insufficiency

KEYTRUDA QLEX can cause primary or secondary adrenal insufficiency. For Grade 2 or higher, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold KEYTRUDA QLEX depending on severity. Adrenal insufficiency occurred in 2% (5/251) of patients receiving KEYTRUDA QLEX in combination with chemotherapy, including Grade 3 (0.4%) and Grade 2 (0.8%) adverse reactions.

Intravenous Pembrolizumab as a Single Agent

Adrenal insufficiency occurred in 0.8% (22/2799) of patients receiving intravenous pembrolizumab, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.3%) reactions. Systemic corticosteroids were required in 77% (17/22) of patients; of these, the majority remained on systemic corticosteroids. Adrenal insufficiency led to permanent discontinuation of intravenous pembrolizumab in <0.1% (1) and withholding in 0.3% (8) of patients. All patients who were withheld reinitiated intravenous pembrolizumab after symptom improvement.

Hypophysitis

KEYTRUDA QLEX can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as indicated. Withhold or permanently discontinue KEYTRUDA QLEX depending on severity.

Intravenous Pembrolizumab as a Single Agent

Hypophysitis occurred in 0.6% (17/2799) of patients receiving intravenous pembrolizumab, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.2%) reactions. Systemic corticosteroids were required in 94% (16/17) of patients; of these, the majority remained on systemic corticosteroids. Hypophysitis led to permanent discontinuation of intravenous pembrolizumab in 0.1% (4) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated intravenous pembrolizumab after symptom improvement.

Thyroid Disorders

KEYTRUDA QLEX can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue KEYTRUDA QLEX depending on severity. Thyroiditis occurred in 0.4% (1/251) of patients receiving KEYTRUDA QLEX in combination with chemotherapy, including Grade 2 (0.4%). Hyperthyroidism occurred in 8% (20/251) of patients receiving KEYTRUDA QLEX in combination with chemotherapy, including Grade 2 (3.2%). Hypothyroidism occurred in 14% (35/251) of patients receiving KEYTRUDA QLEX in combination with chemotherapy, including Grade 2 (11%).

Intravenous Pembrolizumab as a Single Agent

Thyroiditis occurred in 0.6% (16/2799) of patients receiving intravenous pembrolizumab, including Grade 2 (0.3%). None discontinued, but intravenous pembrolizumab was withheld in <0.1% (1) of patients.

Hyperthyroidism occurred in 3.4% (96/2799) of patients receiving intravenous pembrolizumab, including Grade 3 (0.1%) and Grade 2 (0.8%). It led to permanent discontinuation of intravenous pembrolizumab in <0.1% (2) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated intravenous pembrolizumab after symptom improvement. Hypothyroidism occurred in 8% (237/2799) of patients receiving intravenous pembrolizumab, including Grade 3 (0.1%) and Grade 2 (6.2%). It led to permanent discontinuation of intravenous pembrolizumab in <0.1% (1) and withholding in 0.5% (14) of patients. All patients who were withheld reinitiated intravenous pembrolizumab after symptom improvement. The majority of patients with hypothyroidism required long-term thyroid hormone replacement. The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC, occurring in 16% of patients receiving intravenous pembrolizumab as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. The incidence of new or worsening hyperthyroidism was higher in 580 patients with resected NSCLC, occurring in 11% of patients receiving intravenous pembrolizumab as a single agent as adjuvant treatment, including Grade 3 (0.2%) hyperthyroidism. The incidence of new or worsening hypothyroidism was higher in 580 patients with resected NSCLC, occurring in 22% of patients receiving intravenous pembrolizumab as a single agent as adjuvant treatment (KEYNOTE-091), including Grade 3 (0.3%) hypothyroidism.

Type 1 Diabetes Mellitus (DM), Which Can Present With Diabetic Ketoacidosis

Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold KEYTRUDA QLEX depending on severity. Type 1 diabetes mellitus occurred in 0.4% (1/251) of patients receiving KEYTRUDA QLEX in combination with chemotherapy.

Intravenous Pembrolizumab as a Single Agent

Type 1 DM occurred in 0.2% (6/2799) of patients receiving intravenous pembrolizumab. It led to permanent discontinuation in <0.1% (1) and withholding of intravenous pembrolizumab in <0.1% (1) of patients. All patients who were withheld reinitiated intravenous pembrolizumab after symptom improvement.

Immune-Mediated Nephritis With Renal Dysfunction

KEYTRUDA QLEX can cause immune-mediated nephritis.

Intravenous Pembrolizumab as a Single Agent

Immune-mediated nephritis occurred in 0.3% (9/2799) of patients receiving intravenous pembrolizumab, including Grade 4 (<0.1%), Grade 3 (0.1%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 89% (8/9) of patients. Nephritis led to permanent discontinuation of intravenous pembrolizumab in 0.1% (3) and withholding in 0.1% (3) of patients. All patients who were withheld reinitiated intravenous pembrolizumab after symptom improvement; of these, none had recurrence. Nephritis resolved in 56% of the 9 patients.

Immune-Mediated Dermatologic Adverse Reactions

KEYTRUDA QLEX can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, has occurred with anti–PD-1/PD-L1 treatments. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes. Withhold or permanently discontinue KEYTRUDA QLEX depending on severity. Immune-mediated dermatologic adverse reactions occurred in 1.6% (4/251) of patients receiving KEYTRUDA QLEX in combination with chemotherapy, including Grade 4 (0.8%) and Grade 3 (0.8%) adverse reactions.

Intravenous Pembrolizumab as a Single Agent

Immune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of patients receiving intravenous pembrolizumab, including Grade 3 (1%) and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 40% (15/38) of patients. These reactions led to permanent discontinuation in 0.1% (2) and withholding of intravenous pembrolizumab in 0.6% (16) of patients. All patients who were withheld reinitiated intravenous pembrolizumab after symptom improvement; of these, 6% had recurrence. The reactions resolved in 79% of the 38 patients.

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received KEYTRUDA QLEX, intravenous pembrolizumab, or were reported with the use of other anti–PD-1/PD-L1 treatments. Severe or fatal cases have been reported for some of these adverse reactions. Cardiac/Vascular: Myocarditis, pericarditis, vasculitis; Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy; Ocular: Uveitis, iritis and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss; Gastrointestinal: Pancreatitis, to include increases in serum amylase and lipase levels, gastritis (2.8%), duodenitis; Musculoskeletal and Connective Tissue: Myositis/polymyositis, rhabdomyolysis (and associated sequelae, including renal failure), arthritis (1.5%), polymyalgia rheumatica; Endocrine: Hypoparathyroidism; Hematologic/Immune: Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection, other transplant (including corneal graft) rejection.

Hypersensitivity and Administration-Related Reactions

KEYTRUDA QLEX can cause severe or life-threatening administration-related reactions, including hypersensitivity and anaphylaxis. In Study MK-3475A-D77, hypersensitivity and administration-related systemic reactions occurred in 3.2% (8/251) of patients receiving KEYTRUDA QLEX, including Grade 2 (2.8%). Monitor patients for signs and symptoms of administration-related systemic reactions including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. Interrupt injection (if not already fully administered) and resume if symptoms resolve for mild or moderate hypersensitivity and administration-related systemic reactions. For severe or life-threatening hypersensitivity and administration-related systemic reactions, stop injection and permanently discontinue KEYTRUDA QLEX.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after anti–PD-1/PD-L1 treatments. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute and chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between anti–PD-1/PD-L1 treatments and allogeneic HSCT. Follow patients closely for evidence of these complications and intervene promptly. Consider the benefit vs risks of using anti–PD-1/PD-L1 treatments prior to or after an allogeneic HSCT.

Increased Mortality in Patients With Multiple Myeloma

In trials in patients with multiple myeloma, the addition of intravenous pembrolizumab to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with an anti–PD-1/PD-L1 treatment in this combination is not recommended outside of controlled trials.

Embryofetal Toxicity

Based on its mechanism of action, KEYTRUDA QLEX can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA QLEX and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions

In Study MK-3475A-D77, when KEYTRUDA QLEX was administered with chemotherapy in metastatic non-small cell lung cancer (NSCLC), serious adverse reactions occurred in 39% of patients. Serious adverse reactions in ≥1% of patients who received KEYTRUDA QLEX were pneumonia (10%), thrombocytopenia (4%), febrile neutropenia (4%), neutropenia (2.8%), musculoskeletal pain (2%), pneumonitis (2%), diarrhea (1.6%), rash (1.2%), respiratory failure (1.2%), and anemia (1.2%). Fatal adverse reactions occurred in 10% of patients including pneumonia (3.2%), febrile neutropenia (1.2%), respiratory failure (1.2%), neutropenic sepsis (0.4%), septic shock (0.4%), parotitis (0.4%), pneumonitis (0.4%), pneumothorax (0.4%), pulmonary embolism (0.4%), neutropenic colitis (0.4%), and seizure (0.4%). KEYTRUDA QLEX was permanently discontinued due to an adverse reaction in 16% of patients. Adverse reactions which resulted in permanent discontinuation of KEYTRUDA QLEX in ≥2% of patients included pneumonia and pneumonitis. Dosage interruptions of KEYTRUDA QLEX due to an adverse reaction occurred in 45% of patients. Adverse reactions which required dosage interruption in ≥2% of patients included neutropenia, anemia, thrombocytopenia, pneumonia, rash, and increased aspartate aminotransferase. The most common adverse reactions (≥20%) were nausea (25%), fatigue (25%), and musculoskeletal pain (21%).

In KEYNOTE-006, intravenous pembrolizumab was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to permanent discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). The most common adverse reactions (≥20%) with intravenous pembrolizumab were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

In KEYNOTE-054, when intravenous pembrolizumab was administered as a single agent to patients with stage III melanoma, intravenous pembrolizumab was permanently discontinued due to adverse reactions in 14% of 509 patients; the most common (≥1%) were pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred in 25% of patients receiving intravenous pembrolizumab. The most common adverse reaction (≥20%) with intravenous pembrolizumab was diarrhea (28%). In KEYNOTE-716, when intravenous pembrolizumab was administered as a single agent to patients with stage IIB or IIC melanoma, adverse reactions occurring in patients with stage IIB or IIC melanoma were similar to those occurring in 1011 patients with stage III melanoma from KEYNOTE-054.

In KEYNOTE-189, when intravenous pembrolizumab was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, intravenous pembrolizumab was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of intravenous pembrolizumab were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions (≥20%) with intravenous pembrolizumab were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).

In KEYNOTE-407, when intravenous pembrolizumab was administered with carboplatin and either paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, intravenous pembrolizumab was discontinued due to adverse reactions in 15% of 101 patients. The most frequent serious adverse reactions reported in at least 2% of patients were febrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions observed in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the exception that increased incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the intravenous pembrolizumab and chemotherapy arm compared to the placebo and chemotherapy arm in KEYNOTE-407.

In KEYNOTE-042, intravenous pembrolizumab was discontinued due to adverse reactions in 19% of 636 patients with advanced NSCLC; the most common were pneumonitis (3%), death due to unknown cause (1.6%), and pneumonia (1.4%). The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia (7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion (2.2%). The most common adverse reaction (≥20%) was fatigue (25%).

In KEYNOTE-010, intravenous pembrolizumab monotherapy was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC; the most common was pneumonitis (1.8%). The most common adverse reactions (≥20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%).

In KEYNOTE-671, adverse reactions occurring in patients with resectable NSCLC receiving intravenous pembrolizumab in combination with platinum-containing chemotherapy, given as neoadjuvant treatment and continued as single-agent adjuvant treatment, were generally similar to those occurring in patients in other clinical trials across tumor types receiving intravenous pembrolizumab in combination with chemotherapy.

The most common adverse reactions (reported in ≥20%) in patients receiving intravenous pembrolizumab in combination with chemotherapy were fatigue/asthenia, nausea, constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea, pyrexia, alopecia, peripheral neuropathy, mucosal inflammation, stomatitis, headache, weight loss, abdominal pain, arthralgia, myalgia, insomnia, palmar-plantar erythrodysesthesia, urinary tract infection, and hypothyroidism.

In the neoadjuvant phase of KEYNOTE-671, when intravenous pembrolizumab was administered in combination with platinum-containing chemotherapy as neoadjuvant treatment, serious adverse reactions occurred in 34% of 396 patients. The most frequent (≥2%) serious adverse reactions were pneumonia (4.8%), venous thromboembolism (3.3%), and anemia (2%). Fatal adverse reactions occurred in 1.3% of patients, including death due to unknown cause (0.8%), sepsis (0.3%), and immune-mediated lung disease (0.3%). Permanent discontinuation of any study drug due to an adverse reaction occurred in 18% of patients who received intravenous pembrolizumab in combination with platinum-containing chemotherapy; the most frequent adverse reactions (≥1%) that led to permanent discontinuation of any study drug were acute kidney injury (1.8%), interstitial lung disease (1.8%), anemia (1.5%), neutropenia (1.5%), and pneumonia (1.3%).

Of the intravenous pembrolizumab-treated patients who received neoadjuvant treatment, 6% of 396 patients did not receive surgery due to adverse reactions. The most frequent (≥1%) adverse reaction that led to cancellation of surgery in the intravenous pembrolizumab arm was interstitial lung disease (1%).

In the adjuvant phase of KEYNOTE-671, when intravenous pembrolizumab was administered as a single agent as adjuvant treatment, serious adverse reactions occurred in 14% of 290 patients. The most frequent serious adverse reaction was pneumonia (3.4%). One fatal adverse reaction of pulmonary hemorrhage occurred. Permanent discontinuation of intravenous pembrolizumab due to an adverse reaction occurred in 12% of patients who received intravenous pembrolizumab as a single agent, given as adjuvant treatment; the most frequent adverse reactions (≥1%) that led to permanent discontinuation of intravenous pembrolizumab were diarrhea (1.7%), interstitial lung disease (1.4%), increased aspartate aminotransferase (1%), and musculoskeletal pain (1%).

Adverse reactions observed in KEYNOTE-091 were generally similar to those occurring in other patients with NSCLC receiving intravenous pembrolizumab as a single agent, with the exception of hypothyroidism (22%), hyperthyroidism (11%), and pneumonitis (7%). Two fatal adverse reactions of myocarditis occurred.

Adverse reactions observed in KEYNOTE-483 were generally similar to those occurring in other patients receiving intravenous pembrolizumab in combination with pemetrexed and platinum chemotherapy.

In KEYNOTE-048, intravenous pembrolizumab monotherapy was discontinued due to adverse events in 12% of 300 patients with HNSCC; the most common adverse reactions leading to permanent discontinuation were sepsis (1.7%) and pneumonia (1.3%). The most common adverse reactions (≥20%) were fatigue (33%), constipation (20%), and rash (20%).

In KEYNOTE-048, when intravenous pembrolizumab was administered in combination with platinum (cisplatin or carboplatin) and FU chemotherapy, intravenous pembrolizumab was discontinued due to adverse reactions in 16% of 276 patients with HNSCC. The most common adverse reactions resulting in permanent discontinuation of intravenous pembrolizumab were pneumonia (2.5%), pneumonitis (1.8%), and septic shock (1.4%). The most common adverse reactions (≥20%) were nausea (51%), fatigue (49%), constipation (37%), vomiting (32%), mucosal inflammation (31%), diarrhea (29%), decreased appetite (29%), stomatitis (26%), and cough (22%).

In KEYNOTE-012, intravenous pembrolizumab was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (≥20%) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC who received intravenous pembrolizumab as a monotherapy, with the exception of increased incidences of facial edema and new or worsening hypothyroidism.

In KEYNOTE-A39, when intravenous pembrolizumab was administered in combination with enfortumab vedotin to patients with locally advanced or metastatic urothelial cancer (n=440), fatal adverse reactions occurred in 3.9% of patients, including acute respiratory failure (0.7%), pneumonia (0.5%), and pneumonitis/ILD (0.2%). Serious adverse reactions occurred in 50% of patients receiving intravenous pembrolizumab in combination with enfortumab vedotin; the serious adverse reactions in ≥2% of patients were rash (6%), acute kidney injury (5%), pneumonitis/ILD (4.5%), urinary tract infection (3.6%), diarrhea (3.2%), pneumonia (2.3%), pyrexia (2%), and hyperglycemia (2%). Permanent discontinuation of intravenous pembrolizumab occurred in 27% of patients. The most common adverse reactions (≥2%) resulting in permanent discontinuation of intravenous pembrolizumab were pneumonitis/ILD (4.8%) and rash (3.4%). The most common adverse reactions (≥20%) occurring in patients treated with intravenous pembrolizumab in combination with enfortumab vedotin were rash (68%), peripheral neuropathy (67%), fatigue (51%), pruritus (41%), diarrhea (38%), alopecia (35%), weight loss (33%), decreased appetite (33%), nausea (26%), constipation (26%), dry eye (24%), dysgeusia (21%), and urinary tract infection (21%).

In KEYNOTE-052, intravenous pembrolizumab was discontinued due to adverse reactions in 11% of 370 patients with locally advanced or metastatic urothelial carcinoma. Serious adverse reactions occurred in 42% of patients; those ≥2% were urinary tract infection, hematuria, acute kidney injury, pneumonia, and urosepsis. The most common adverse reactions (≥20%) were fatigue (38%), musculoskeletal pain (24%), decreased appetite (22%), constipation (21%), rash (21%), and diarrhea (20%).

In KEYNOTE-045, intravenous pembrolizumab was discontinued due to adverse reactions in 8% of 266 patients with locally advanced or metastatic urothelial carcinoma. The most common adverse reaction resulting in permanent discontinuation of intravenous pembrolizumab was pneumonitis (1.9%). Serious adverse reactions occurred in 39% of intravenous pembrolizumab-treated patients; those ≥2% were urinary tract infection, pneumonia, anemia, and pneumonitis. The most common adverse reactions (≥20%) in patients who received intravenous pembrolizumab were fatigue (38%), musculoskeletal pain (32%), pruritus (23%), decreased appetite (21%), nausea (21%), and rash (20%).

In KEYNOTE-057, intravenous pembrolizumab was discontinued due to adverse reactions in 11% of 148 patients with high-risk NMIBC. The most common adverse reaction resulting in permanent discontinuation of intravenous pembrolizumab was pneumonitis (1.4%). Serious adverse reactions occurred in 28% of patients; those ≥2% were pneumonia (3%), cardiac ischemia (2%), colitis (2%), pulmonary embolism (2%), sepsis (2%), and urinary tract infection (2%). The most common adverse reactions (≥20%) were fatigue (29%), diarrhea (24%), and rash (24%).

Adverse reactions occurring in patients with MSI-H or dMMR CRC were similar to those occurring in patients with melanoma or NSCLC who received intravenous pembrolizumab as a monotherapy.

In KEYNOTE-158 and KEYNOTE-164, adverse reactions occurring in patients with MSI-H or dMMR cancer were similar to those occurring in patients with other solid tumors who received intravenous pembrolizumab as a single agent.

In KEYNOTE-811, when intravenous pembrolizumab was administered in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, intravenous pembrolizumab was discontinued due to adverse reactions in 6% of 217 patients with locally advanced unresectable or metastatic HER2+ gastric or GEJ adenocarcinoma. The most common adverse reaction resulting in permanent discontinuation was pneumonitis (1.4%). In the intravenous pembrolizumab arm vs placebo, there was a difference of ≥5% incidence between patients treated with intravenous pembrolizumab vs standard of care for diarrhea (53% vs 44%) and nausea (49% vs 44%).

In KEYNOTE-859, when intravenous pembrolizumab was administered in combination with fluoropyrimidine- and platinum-containing chemotherapy, serious adverse reactions occurred in 45% of 785 patients. Serious adverse reactions in >2% of patients included pneumonia (4.1%), diarrhea (3.9%), hemorrhage (3.9%), and vomiting (2.4%). Fatal adverse reactions occurred in 8% of patients who received intravenous pembrolizumab, including infection (2.3%) and thromboembolism (1.3%). Intravenous pembrolizumab was permanently discontinued due to adverse reactions in 15% of patients. The most common adverse reactions resulting in permanent discontinuation of intravenous pembrolizumab (≥1%) were infections (1.8%) and diarrhea (1.0%). The most common adverse reactions (reported in ≥20%) in patients receiving intravenous pembrolizumab in combination with chemotherapy were peripheral neuropathy (47%), nausea (46%), fatigue (40%), diarrhea (36%), vomiting (34%), decreased appetite (29%), abdominal pain (26%), palmar-plantar erythrodysesthesia syndrome (25%), constipation (22%), and weight loss (20%).

In KEYNOTE-590, when intravenous pembrolizumab was administered with cisplatin and fluorouracil to patients with metastatic or locally advanced esophageal or GEJ (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma who were not candidates for surgical resection or definitive chemoradiation, intravenous pembrolizumab was discontinued due to adverse reactions in 15% of 370 patients. The most common adverse reactions resulting in permanent discontinuation of intravenous pembrolizumab (≥1%) were pneumonitis (1.6%), acute kidney injury (1.1%), and pneumonia (1.1%). The most common adverse reactions (≥20%) with intravenous pembrolizumab in combination with chemotherapy were nausea (67%), fatigue (57%), decreased appetite (44%), constipation (40%), diarrhea (36%), vomiting (34%), stomatitis (27%), and weight loss (24%).

Adverse reactions occurring in patients with esophageal cancer who received intravenous pembrolizumab as a monotherapy were similar to those occurring in patients with melanoma or NSCLC who received intravenous pembrolizumab as a monotherapy.

In KEYNOTE-A18, when intravenous pembrolizumab was administered with CRT (cisplatin plus external beam radiation therapy [EBRT] followed by brachytherapy [BT]) to patients with FIGO 2014 Stage III-IVA cervical cancer, fatal adverse reactions occurred in 1.4% of 292 patients, including 1 case each (0.3%) of large intestinal perforation, urosepsis, sepsis, and vaginal hemorrhage. Serious adverse reactions occurred in 30% of patients; those ≥1% included urinary tract infection (2.7%), urosepsis (1.4%), and sepsis (1%). Intravenous pembrolizumab was discontinued for adverse reactions in 7% of patients. The most common adverse reaction (≥1%) resulting in permanent discontinuation was diarrhea (1%). For patients treated with intravenous pembrolizumab in combination with CRT, the most common adverse reactions (≥10%) were nausea (56%), diarrhea (50%), vomiting (33%), urinary tract infection (32%), fatigue (26%), hypothyroidism (20%), constipation (18%), decreased appetite and weight loss (17% each), abdominal pain and pyrexia (12% each), hyperthyroidism, dysuria, rash (11% each), and pelvic pain (10%).

In KEYNOTE-826, when intravenous pembrolizumab was administered in combination with paclitaxel and cisplatin or paclitaxel and carboplatin, with or without bevacizumab (n=307), to patients with persistent, recurrent, or first-line metastatic cervical cancer regardless of tumor PD-L1 expression who had not been treated with chemotherapy except when used concurrently as a radio-sensitizing agent, fatal adverse reactions occurred in 4.6% of patients, including 3 cases of hemorrhage, 2 cases each of sepsis and due to unknown causes, and 1 case each of acute myocardial infarction, autoimmune encephalitis, cardiac arrest, cerebrovascular accident, femur fracture with perioperative pulmonary embolus, intestinal perforation, and pelvic infection. Serious adverse reactions occurred in 50% of patients receiving intravenous pembrolizumab in combination with chemotherapy with or without bevacizumab; those ≥3% were febrile neutropenia (6.8%), urinary tract infection (5.2%), anemia (4.6%), and acute kidney injury and sepsis (3.3% each).

Intravenous pembrolizumab was discontinued in 15% of patients due to adverse reactions. The most common adverse reaction resulting in permanent discontinuation (≥1%) was colitis (1%).

For patients treated with intravenous pembrolizumab, chemotherapy, and bevacizumab (n=196), the most common adverse reactions (≥20%) were peripheral neuropathy (62%), alopecia (58%), anemia (55%), fatigue/asthenia (53%), nausea and neutropenia (41% each), diarrhea (39%), hypertension and thrombocytopenia (35% each), constipation and arthralgia (31% each), vomiting (30%), urinary tract infection (27%), rash (26%), leukopenia (24%), hypothyroidism (22%), and decreased appetite (21%).

For patients treated with intravenous pembrolizumab in combination with chemotherapy with or without bevacizumab, the most common adverse reactions (≥20%) were peripheral neuropathy (58%), alopecia (56%), fatigue (47%), nausea (40%), diarrhea (36%), constipation (28%), arthralgia (27%), vomiting (26%), hypertension and urinary tract infection (24% each), and rash (22%).

In KEYNOTE-158, intravenous pembrolizumab was discontinued due to adverse reactions in 8% of 98 patients with previously treated recurrent or metastatic cervical cancer. Serious adverse reactions occurred in 39% of patients receiving intravenous pembrolizumab; the most frequent included anemia (7%), fistula, hemorrhage, and infections [except urinary tract infections] (4.1% each). The most common adverse reactions (≥20%) were fatigue (43%), musculoskeletal pain (27%), diarrhea (23%), pain and abdominal pain (22% each), and decreased appetite (21%).

In KEYNOTE-394, intravenous pembrolizumab was discontinued due to adverse reactions in 13% of 299 patients with previously treated hepatocellular carcinoma. The most common adverse reaction resulting in permanent discontinuation of intravenous pembrolizumab was ascites (2.3%). The most common adverse reactions in patients receiving intravenous pembrolizumab (≥10%) were pyrexia (18%), rash (18%), diarrhea (16%), decreased appetite (15%), pruritus (12%), upper respiratory tract infection (11%), cough (11%), and hypothyroidism (10%).

In KEYNOTE-966, when intravenous pembrolizumab was administered in combination with gemcitabine and cisplatin, intravenous pembrolizumab was discontinued for adverse reactions in 15% of 529 patients with locally advanced unresectable or metastatic biliary tract cancer. The most common adverse reaction resulting in permanent discontinuation of intravenous pembrolizumab (≥1%) was pneumonitis (1.3%). Adverse reactions leading to the interruption of intravenous pembrolizumab occurred in 55% of patients. The most common adverse reactions or laboratory abnormalities leading to interruption of intravenous pembrolizumab (≥2%) were decreased neutrophil count (18%), decreased platelet count (10%), anemia (6%), decreased white blood cell count (4%), pyrexia (3.8%), fatigue (3.0%), cholangitis (2.8%), increased ALT (2.6%), increased AST (2.5%), and biliary obstruction (2.3%).

In KEYNOTE-017 and KEYNOTE-913, adverse reactions occurring in patients with MCC (n=105) were generally similar to those occurring in patients with melanoma or NSCLC who received intravenous pembrolizumab as a single agent.

In KEYNOTE-426, when intravenous pembrolizumab was administered in combination with axitinib, fatal adverse reactions occurred in 3.3% of 429 patients. Serious adverse reactions occurred in 40% of patients, the most frequent (≥1%) were hepatotoxicity (7%), diarrhea (4.2%), acute kidney injury (2.3%), dehydration (1%), and pneumonitis (1%). Permanent discontinuation due to an adverse reaction occurred in 31% of patients; intravenous pembrolizumab only (13%), axitinib only (13%), and the combination (8%); the most common were hepatotoxicity (13%), diarrhea/colitis (1.9%), acute kidney injury (1.6%), and cerebrovascular accident (1.2%). The most common adverse reactions (≥20%) were diarrhea (56%), fatigue/asthenia (52%), hypertension (48%), hepatotoxicity (39%), hypothyroidism (35%), decreased appetite (30%), palmar-plantar erythrodysesthesia (28%), nausea (28%), stomatitis/mucosal inflammation (27%), dysphonia (25%), rash (25%), cough (21%), and constipation (21%).

In KEYNOTE-564, when intravenous pembrolizumab was administered as a single agent for the adjuvant treatment of renal cell carcinoma, serious adverse reactions occurred in 20% of patients receiving intravenous pembrolizumab; the serious adverse reactions (≥1%) were acute kidney injury, adrenal insufficiency, pneumonia, colitis, and diabetic ketoacidosis (1% each). Fatal adverse reactions occurred in 0.2% including 1 case of pneumonia. Discontinuation of intravenous pembrolizumab due to adverse reactions occurred in 21% of 488 patients; the most common (≥1%) were increased ALT (1.6%), colitis (1%), and adrenal insufficiency (1%). The most common adverse reactions (≥20%) were musculoskeletal pain (41%), fatigue (40%), rash (30%), diarrhea (27%), pruritus (23%), and hypothyroidism (21%).

In KEYNOTE-868, when intravenous pembrolizumab was administered in combination with chemotherapy (paclitaxel and carboplatin) to patients with advanced or recurrent endometrial carcinoma (n=382), serious adverse reactions occurred in 35% of patients receiving intravenous pembrolizumab in combination with chemotherapy, compared to 19% of patients receiving placebo in combination with chemotherapy (n=377). Fatal adverse reactions occurred in 1.6% of patients receiving intravenous pembrolizumab in combination with chemotherapy, including COVID-19 (0.5%) and cardiac arrest (0.3%). Intravenous pembrolizumab was discontinued for an adverse reaction in 14% of patients. Adverse reactions occurring in patients treated with intravenous pembrolizumab and chemotherapy were generally similar to those observed with intravenous pembrolizumab alone or chemotherapy alone, with the exception of rash (33% all Grades; 2.9% Grades 3-4).

Adverse reactions occurring in patients with MSI-H or dMMR endometrial carcinoma who received intravenous pembrolizumab as a single agent were similar to those occurring in patients with melanoma or NSCLC who received intravenous pembrolizumab as a single agent.

Adverse reactions occurring in patients with recurrent or metastatic cSCC or locally advanced cSCC were similar to those occurring in patients with melanoma or NSCLC who received intravenous pembrolizumab as a monotherapy.

In KEYNOTE-522, when intravenous pembrolizumab was administered with neoadjuvant chemotherapy (carboplatin and paclitaxel followed by doxorubicin or epirubicin and cyclophosphamide) followed by surgery and continued adjuvant treatment with intravenous pembrolizumab as a single agent (n=778) to patients with newly diagnosed, previously untreated, high-risk early-stage TNBC, fatal adverse reactions occurred in 0.9% of patients, including 1 each of adrenal crisis, autoimmune encephalitis, hepatitis, pneumonia, pneumonitis, pulmonary embolism, and sepsis in association with multiple organ dysfunction syndrome and myocardial infarction. Serious adverse reactions occurred in 44% of patients receiving intravenous pembrolizumab; those ≥2% were febrile neutropenia (15%), pyrexia (3.7%), anemia (2.6%), and neutropenia (2.2%). Intravenous pembrolizumab was discontinued in 20% of patients due to adverse reactions. The most common reactions (≥1%) resulting in permanent discontinuation were increased ALT (2.7%), increased AST (1.5%), and rash (1%). The most common adverse reactions (≥20%) in patients receiving intravenous pembrolizumab were fatigue (70%), nausea (67%), alopecia (61%), rash (52%), constipation (42%), diarrhea and peripheral neuropathy (41% each), stomatitis (34%), vomiting (31%), headache (30%), arthralgia (29%), pyrexia (28%), cough (26%), abdominal pain (24%), decreased appetite (23%), insomnia (21%), and myalgia (20%).

In KEYNOTE-355, when intravenous pembrolizumab and chemotherapy (paclitaxel, paclitaxel protein-bound, or gemcitabine and carboplatin) were administered to patients with locally recurrent unresectable or metastatic TNBC who had not been previously treated with chemotherapy in the metastatic setting (n=596), fatal adverse reactions occurred in 2.5% of patients, including cardio-respiratory arrest (0.7%) and septic shock (0.3%). Serious adverse reactions occurred in 30% of patients receiving intravenous pembrolizumab in combination with chemotherapy; the serious reactions in ≥2% were pneumonia (2.9%), anemia (2.2%), and thrombocytopenia (2%). Intravenous pembrolizumab was discontinued in 11% of patients due to adverse reactions. The most common reactions resulting in permanent discontinuation (≥1%) were increased ALT (2.2%), increased AST (1.5%), and pneumonitis (1.2%). The most common adverse reactions (≥20%) in patients receiving intravenous pembrolizumab in combination with chemotherapy were fatigue (48%), nausea (44%), alopecia (34%), diarrhea and constipation (28% each), vomiting and rash (26% each), cough (23%), decreased appetite (21%), and headache (20%).

Lactation

Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 4 months after the last dose.

Pediatric Use

In KEYNOTE-051, 173 pediatric patients (including 108 pediatric patients aged 12 years to 17 years) were administered intravenous pembrolizumab 2 mg/kg every 3 weeks. The median duration of exposure was 2.1 months (range: 1 day to 25 months).

The safety and effectiveness of KEYTRUDA QLEX for the treatment of pediatric patients 12 years and older who weigh greater than 40 kg have been established for:

Stage IIB, IIC, or III melanoma following complete resection
Unresectable or metastatic microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) solid tumors
Recurrent locally advanced or metastatic Merkel cell carcinoma
Use of KEYTRUDA QLEX in pediatric patients for these indications is supported by evidence from adequate and well-controlled studies of intravenous pembrolizumab in adults and additional pharmacokinetic and safety data for intravenous pembrolizumab in pediatric patients 12 years and older. Pembrolizumab exposures in pediatric patients 12 years and older who weigh greater than 40 kg are predicted to be within range of those observed in adults at the same dosage.

The safety and effectiveness of KEYTRUDA QLEX have not been established in pediatric patients younger than 12 years of age for the treatment of melanoma, MCC, MSI-H or dMMR cancer.

The safety and effectiveness of KEYTRUDA QLEX have not been established in pediatric patients for other approved indications shown.

Adverse reactions that occurred at a ≥10% higher rate in pediatric patients when compared to adults were pyrexia (33%), leukopenia (30%), vomiting (29%), neutropenia (28%), headache (25%), abdominal pain (23%), thrombocytopenia (22%), Grade 3 anemia (17%), decreased lymphocyte count (13%), and decreased white blood cell count (11%).

Geriatric Use

Of the 564 patients with locally advanced or metastatic urothelial cancer treated with intravenous pembrolizumab in combination with enfortumab vedotin, 44% (n=247) were 65-74 years and 26% (n=144) were 75 years or older. No overall differences in safety or effectiveness were observed between patients 65 years of age or older and younger patients. Patients 75 years of age or older treated with intravenous pembrolizumab in combination with enfortumab vedotin experienced a higher incidence of fatal adverse reactions than younger patients. The incidence of fatal adverse reactions was 4% in patients younger than 75 and 7% in patients 75 years or older.

On September 19, 2025 IMUNON, Inc. (Nasdaq: IMNN), a clinical-stage company in Phase 3 development with its DNA-mediated immunotherapy, reported that new translational data from the Phase 2 OVATION 2 Study of IMNN-001, its investigational therapy for the treatment of women with newly diagnosed advanced ovarian cancer, will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Special Conference in Cancer Research: Advances in Ovarian Cancer Research, being held September 19-21, 2025, in Denver, Colorado (Press release, IMUNON, SEP 19, 2025, View Source [SID1234656102]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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IMNN-001, based on IMUNON’s proprietary TheraPlas technology platform, is an interleukin-12 (IL-12) DNA plasmid vector incorporated into a novel nanoparticle delivery system, enabling cell transfection followed by persistent, local production and secretion of the IL-12 protein in the tumor microenvironment. IL-12 is a powerful pluripotent cytokine known for inducing strong anti-cancer immunity by promoting T-lymphocyte and natural killer cell proliferation while inhibiting tumor-mediated immune suppression. IMNN-001 is the first therapy to achieve a clinically effective response in advanced (stage IIIC/IV) ovarian cancer including benefits in both progression-free survival and overall survival in a first-line treatment setting when used with standard of care chemotherapy.

Details of the AACR (Free AACR Whitepaper) presentation:

Abstract Title: IMNN-001, an IL-12 gene therapy, added to Neo/Adjuvant chemotherapy safely turns the tumor microenvironment cold-to-hot in newly diagnosed epithelial ovarian cancer (EOC)
Presenting Author: Douglas V. Faller, M.D., Ph.D., Chief Medical Officer, IMUNON
Date: Saturday, September 20, 2025
Time: 6:35-8:05 p.m. ET
Abstract Number: B050

About the OVATION 3 Study

OVATION 3 is IMUNON’s pivotal Phase 3 study of IMMN-001, an IL-12 gene-mediated immunotherapy, in women with advanced epithelial ovarian cancer. The study is supported with unprecedented overall survival (OS) data from a large, 112-patient, randomized Phase 2 study showing the following:

Median 13-month increase in OS (HR 0.70) and median 3-month increase in PFS (HR 0.79) in IMNN-001 treatment arm compared to standard of care alone.
Better therapeutic effect observed with IMNN-001 treatment compared to the control arm (p=0.0375), as shown by mean 6.5-month extension of time free of progression or death (PFS + OS) captured in totality of treatment effect.
Use of poly ADP-ribose polymerase (PARP) inhibitors as part of maintenance therapy further enhanced outcomes, with median OS not yet reached in IMNN-001 treatment arm as patients surpass >5 years since randomization in the trial compared to 37 months on standard of care (HR 0.42).
While not powered for significance, the results from the OVATION 2 Study nonetheless have resulted in invitations to present at both ASCO (Free ASCO Whitepaper) and ESMO (Free ESMO Whitepaper) annual meetings and publication in the peer-reviewed journal Gynecologic Oncology.

OVATION 3 is currently enrolling patients at four trial sites with up to 46 additional sites being considered for activation.

On September 19, 2025 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it obtained regulatory approval from the Ministry of Health, Labour and Welfare for the anti-cancer agent/humanized anti-PD-L1 monoclonal antibody Tecentriq Intravenous Infusion [generic name: atezolizumab (genetical recombination)] for an additional indication of relapsed or refractory extranodal natural killer/T-cell lymphoma, nasal type (ENKL) (Press release, Chugai, SEP 19, 2025, View Source;category= [SID1234656076]). Tecentriq is the first immune-checkpoint inhibitor approved in Japan for this disease.

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"We are very pleased that we can offer Tecentriq as a new treatment option for ENKL in adults and children 12 years and older. ENKL is a rare type of malignant lymphoma that primarily develops in the nasal cavity. In advanced stages, approximately 60% of patients relapse after initial treatment, and there is no established standard therapy after relapse. We will continue our efforts to provide information on the proper use of Tecentriq in order to contribute to the patients with ENKL," said Chugai’s President and CEO, Dr. Osamu Okuda.

This approval is based on the results from the phase II ATTACK study initiated by investigators in Japan including National Cancer Center Hospital, which evaluated the efficacy and safety of Tecentriq in patients with R/R ENKL.

In addition to the approval of this expanded indication, we have also received additional approval for a 4-weekly dosing regimen in the "dosage and administration" for existing indications in lung cancer and breast cancer. The additional options in dosing intervals will enable more flexible treatment planning. This is expected to improve convenience for patients and healthcare professionals by reducing the number of hospital visits and lessening the burden on both.

Chugai Pharmaceutical, a leading company in the oncology field, remains committed to addressing unmet medical needs in cancer treatment with innovative medicines, supporting patients and healthcare professionals.

Approval Information *Newly added or revised description (underlined)

All indications: The initial dose of Tecentriq must be administered over 60 minutes. If the first infusion is tolerated, all subsequent infusions may be administered over 30 minutes.

Indications Dosage and administration
Unresectable, advanced or recurrent non-small cell lung cancer
For patients with chemotherapy-naïve unresectable advanced or recurrent non-squamous non-small cell lung cancer
The usual adult dosage is 1200 mg atezolizumab (genetical recombination) administered by intravenous infusion once every 3 weeks.
Subsequently, when administered as monotherapy, atezolizumab (genetical recombination) is administered as an intravenous infusion either 1200 mg once every 3 weeks or 1680 mg once every 4 weeks.
For patients with chemotherapy-naïve PD-L1 positve unresectable advanced or recurrent non-small cell lung cancer
The usual adult dosage of atezolizumab (genetical recombination) is either 1200 mg once every 3 weeks or 1680 mg once every 4 weeks administered by intravenous infusion.

For patients with unresectable advanced or recurrent non-small cell lung cancer previously treated with chemotherapy
The usual adult dosage of atezolizumab (genetical recombination) is either 1200 mg once every 3 weeks or 1680 mg once every 4 weeks administered by intravenous infusion.

PD-L1-positive adjuvant non-small cell lung cancer The usual adult dosage of atezolizumab (genetical recombination) is either 1200 mg once every 3 weeks or 1680 mg once every 4 weeks administered by intravenous infusion. The dosage period is up to 12 months.
Extensive-stage small cell lung cancer The usual adult dosage is 1200 mg atezolizumab (genetical recombination) in combination with carboplatin and etoposide by intravenous infusion once every 3 weeks for 4 doses.
This is followed by atezolizumab (genetical recombination) 1200 mg administered as an intravenous infusion once every 3 weeks or 1680 mg once every 4 weeks.
Unresectable hepatocellular carcinoma The usual adult dosage is 1200 mg atezolizumab (genetical recombination) in combination with bevacizumab administered by intravenous infusion once every 3 weeks.
PD-L1-positive, hormone receptor-negative and HER2-negative inoperable or recurrent breast cancer The usual adult dosage of atezolizumab (genetical recombination) in combination with nab-paclitaxel (albumin-bound) is either 840 mg once every 2 weeks or 1680 mg once every 4 weeks administered by intravenous infusion.
Unresectable alveolar soft part sarcoma The usual adult dosage is 1200 mg atezolizumab (genetical recombination) administered by intravenous infusion once every 3 weeks. The usual dose for children over 2 years old is 15 mg/kg (weight) (max 1200 mg) atezolizumab (genetical recombination) administered by intravenous infusion once every 3 weeks.
Relapsed or refractory extranodal natural killer/T-cell lymphoma, nasal type The usual adult dosage of 1200 mg atezolizumab (genetical recombination) administered by intravenous infusion once every 3 weeks. The usual dose for patients aged 12 to < 18 years is 15 mg/kg (body weight) atezolizumab (genetical recombination) (max 1200 mg) administered by intravenous infusion once every 3 weeks.
About the ATTACK study1
ATTACK study (NCCH1903, jRCT2031190177) is a Japanese Phase II, multicenter, open-label, single-arm study led by physicians including National Cancer Center Hospital to evaluate the efficacy and safety of Tecentriq in patients with relapsed or refractory extranodal natural killer/T-cell lymphoma, nasal type. The study enrolled 14 patients to investigate safety and efficacy. The primary endpoint is the independent review committee (IRC)-assessed overall response rate. Key secondary endpoints include progression-free survival, and overall survival.
The ATTACK study is being conducted as a substudy of the MASTER KEY project, which promotes the development of treatments for rare cancers through industry-academia collaboration with the National Cancer Center Hospital.

About extranodal natural killer/T-cell lymphoma, nasal type (ENKL)
ENKL is a form of malignant lymphoma that primarily affects the nasal cavity. It can occur in individuals of all ages, from children to adults.2,3,4 ENKL is rare, accounting for approximately 0.68% of all malignant lymphoma cases (annual incidence: about 36,000 cases) in Japan.5 For patients with advanced ENKL, about 60% experience relapse following initial treatment.6,7 Relapsed or refractory ENKL has a poor prognosis, and there is currently no established standard treatment.

About Tecentriq8
Tecentriq is a cancer immune-checkpoint inhibitor targeting PD-L1, which is a protein expressed on tumor and tumor-infiltrating immune cells. PD-L1 blocks T cell activity by binding with PD-1 and B7.1 receptors on the T cell surface. By inhibiting PD-L1, Tecentriq may enable the activation of T cells and boost immune response against cancer cells. In Japan, Tecentriq was launched in April 2018 and has obtained approval for 5 indications (non-small cell lung cancer, extensive-stage small cell lung cancer, breast cancer, hepatocellular carcinoma and alveolar soft part sarcoma).

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