On May 25, 2023 Bayer reported that it will highlight scientific research in oncology at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place from June 2-6, 2023 (Press release, Bayer, MAY 25, 2023, View Source [SID1234632122]). These presentations continue to underscore the company’s commitment to drive treatment approaches through science and innovation in the oncology space.

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Data featuring NUBEQA (darolutamide) and Xofigo (radium Ra 223 dichloride) will be showcased at ASCO (Free ASCO Whitepaper). NUBEQA data includes results from the DEAR trial, a retrospective, observational study evaluating real-world evidence (RWE) in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). Additionally, investigational NUBEQA data includes ARASEC, an ongoing U.S.-based open-label study evaluating NUBEQA versus androgen deprivation therapy (ADT), as well as ARAMON, an ongoing, randomized open-label Phase II study on serum testosterone levels in patients with hormone-naive prostate cancer, will be featured. NUBEQA is currently indicated in the U.S. for the treatment of adult patients with metastatic hormone-sensitive prostate cancer (mHSPC) in combination with docetaxel and for the treatment of adult patients with nmCRPC.1

Real-world safety and effectiveness data from the prospective, observational REASSURE study involving patients with metastatic castration-resistant prostate cancer (mCRPC) treated with Xofigo will also be presented. Xofigo is indicated for the treatment of patients with mCRPC, symptomatic bone metastases, and no known visceral metastatic disease.2

Updated results from NAVIGATE and SCOUT studies will be presented for Vitrakvi (larotrectinib) in TRK fusion cancer in adult and pediatric patients across solid tumor types. Long-term efficacy and safety data of Vitrakvi in adult patients with TRK fusion lung cancer and thyroid carcinoma (TC) will also be presented. Additionally, an oral presentation of Phase II investigator-initiated research featuring pediatric patients with newly diagnosed infantile fibrosarcoma (IFS) treated with Vitrakvi will be highlighted. Vitrakvi is approved for the treatment of adult and pediatric patients with solid tumors that have a NTRK gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment. Patients should be selected for therapy based on a FDA-approved test. This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.3

Additional data featuring Bayer’s oncology pipeline will include an oral presentation on the initial results from a first-in-human, Phase I study of immunomodulatory aryl hydrocarbon receptor (AhR) inhibitor BAY2416964 in patients with advanced solid tumors. The six-year safety and efficacy results from CHRONOS-1 study analyzing Aliqopa (copanlisib) in patients with relapsed or refractory follicular lymphoma (FL) will also be presented. Aliqopa is indicated for the treatment of adult patients with relapsed FL who have received at least two prior systemic therapies. Accelerated approval was granted for this indication based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.4

Bayer presentations at the 2023 ASCO (Free ASCO Whitepaper) Annual Meeting are listed below:

Darolutamide

Abstract title: Comparative real-world (RW) evidence on darolutamide (Daro), enzalutamide (Enza), and apalutamide (Apa) for patients (Pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) in the United States: DEAR
Abstract 5097; June 3, 8:00am CDT
Abstract title: Open-label study of darolutamide plus androgen-deprivation therapy (ADT) vs ADT in metastatic hormone-sensitive prostate cancer using an external control arm (ARASEC)
Abstract TPS5112; June 3, 8:00am CDT
Abstract title: A phase 2, randomized, open-label study comparing the effects of darolutamide versus enzalutamide monotherapy on serum testosterone levels in patients with hormone-naive prostate cancer: ARAMON study
Abstract TPS5111; June 3, 8:00am CDT
Radium-223 dichloride (Ra-223)

Abstract title: Real-world safety and effectiveness of radium-223 (223Ra) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated in the US: The non-interventional REASSURE study
Abstract 5050; June 3, 8:00am CDT
Larotrectinib

Abstract title: Larotrectinib long-term efficacy and safety in adult patients (pts) with tropomyosin receptor kinase (TRK) fusion cancer
Abstract 3141; June 3, 8:00am CDT
Abstract title: Long-term efficacy and safety of larotrectinib in patients with tropomyosin receptor kinase (TRK) fusion lung cancer
Abstract 9056; June 4, 8:00am CDT
Abstract title: Larotrectinib (laro) long-term efficacy and safety in patients (pts) with tropomyosin receptor kinase (TRK) fusion thyroid carcinoma (TC)
Abstract 6091; June 5, 1:15pm CDT
Abstract title: Phase 2 study of larotrectinib in children with newly diagnosed infantile fibrosarcoma (IFS): Children’s Oncology Group (COG) ADVL1823 cohort A
Abstract 10008; June 4, 12:09pm CDT
Pipeline

Abstract title: Initial results from a first-in-human, phase I study of immunomodulatory aryl hydrocarbon receptor (AhR) inhibitor BAY2416964 in patients with advanced solid tumors
Abstract 2502; June 4, 9:57am CDT
Abstract title: Six-year safety and efficacy results from the CHRONOS-1 study of the PI3K inhibitor copanlisib in patients with relapsed or refractory follicular lymphoma
Abstract 7555; June 5, 8:00am CDT
Oncology RWE Non-Product Related

Abstract Title: Using real-world evidence (RWE) in regulatory decision making: A study of 6 oncology approvals with RWE included in the product label
Abstract 6611; June 3, 1:15pm CDT
About NUBEQA (darolutamide)1

NUBEQA is an androgen receptor inhibitor (ARi) with a distinct chemical structure that competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription.1

On July 30, 2019, the FDA approved NUBEQA (darolutamide) based on the ARAMIS trial, a randomized, double-blind, placebo-controlled, multi-center Phase III study, which evaluated the safety and efficacy of oral NUBEQA in patients with non-metastatic castration-resistant prostate cancer (nmCRPC).

NUBEQA is also being investigated in additional studies across various stages of prostate cancer, including in the ARANOTE Phase III trial evaluating NUBEQA plus ADT versus ADT alone for metastatic hormone-sensitive prostate cancer (mHSPC), as well as in the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) led international Phase III co-operative group DASL-HiCaP (ANZUP1801) trial evaluating NUBEQA as an adjuvant treatment for localized prostate cancer with very high risk of recurrence. Information about these trials can be found at www.clinicaltrials.gov.

Developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company, NUBEQA is indicated for the treatment of adults with nmCRPC or with mHSPC in combination with docetaxel.1 Filings in other regions are underway or planned.

INDICATIONS

NUBEQA (darolutamide) is an androgen receptor inhibitor indicated for the treatment of adult patients with:

Non-metastatic castration-resistant prostate cancer (nmCRPC)
Metastatic hormone-sensitive prostate cancer (mHSPC) in combination with docetaxel
IMPORTANT SAFETY INFORMATION

Warnings & Precautions

Ischemic Heart Disease – In a study of patients with nmCRPC (ARAMIS), ischemic heart disease occurred in 3.2% of patients receiving NUBEQA versus 2.5% receiving placebo, including Grade 3-4 events in 1.7% vs. 0.4%, respectively. Ischemic events led to death in 0.3% of patients receiving NUBEQA vs. 0.2% receiving placebo. In a study of patients with mHSPC (ARASENS), ischemic heart disease occurred in 2.9% of patients receiving NUBEQA with docetaxel vs. 2% receiving placebo with docetaxel, including Grade 3-4 events in 1.3% vs. 1.1%, respectively. Ischemic events led to death in 0.3% of patients receiving NUBEQA with docetaxel vs. 0% receiving placebo with docetaxel. Monitor for signs and symptoms of ischemic heart disease. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue NUBEQA for Grade 3-4 ischemic heart disease.

Seizure – In ARAMIS, Grade 1-2 seizure occurred in 0.2% of patients receiving NUBEQA vs. 0.2% receiving placebo. Seizure occurred 261 and 456 days after initiation of NUBEQA. In ARASENS, seizure occurred in 0.6% of patients receiving NUBEQA with docetaxel, including one Grade 3 event, vs. 0.2% receiving placebo with docetaxel. Seizure occurred 38 to 340 days after initiation of NUBEQA. It is unknown whether anti-epileptic medications will prevent seizures with NUBEQA. Advise patients of the risk of developing a seizure while receiving NUBEQA and of engaging in any activity where sudden loss of consciousness could cause harm to themselves or others. Consider discontinuation of NUBEQA in patients who develop a seizure during treatment.

Embryo-Fetal Toxicity – Safety and efficacy of NUBEQA have not been established in females. NUBEQA can cause fetal harm and loss of pregnancy. Advise males with female partners of reproductive potential to use effective contraception during treatment with NUBEQA and for 1 week after the last dose.

Adverse Reactions

In ARAMIS, serious adverse reactions occurred in 25% of patients receiving NUBEQA vs. 20% of patients receiving placebo. Serious adverse reactions in ≥1% of patients who received NUBEQA included urinary retention, pneumonia, and hematuria. Fatal adverse reactions occurred in 3.9% of patients receiving NUBEQA vs. 3.2% of patients receiving placebo. Fatal adverse reactions in patients who received NUBEQA included death (0.4%), cardiac failure (0.3%), cardiac arrest (0.2%), general physical health deterioration (0.2%), and pulmonary embolism (0.2%). The most common adverse reactions (>2% with a ≥2% increase over placebo), including laboratory test abnormalities, were increased AST, decreased neutrophil count, fatigue, increased bilirubin, pain in extremity, and rash. Clinically relevant adverse reactions occurring in ≥2% of patients treated with NUBEQA included ischemic heart disease and heart failure.

In ARASENS, serious adverse reactions occurred in 45% of patients receiving NUBEQA with docetaxel vs. 42% of patients receiving placebo with docetaxel. Serious adverse reactions in ≥2% of patients who received NUBEQA with docetaxel included febrile neutropenia (6%), decreased neutrophil count (2.8%), musculoskeletal pain (2.6%), and pneumonia (2.6%). Fatal adverse reactions occurred in 4% of patients receiving NUBEQA with docetaxel vs. 4% of patients receiving placebo with docetaxel. Fatal adverse reactions in patients who received NUBEQA included COVID-19/COVID-19 pneumonia (0.8%), myocardial infarction (0.3%), and sudden death (0.3%). The most common adverse reactions (≥10% with a ≥2% increase over placebo with docetaxel) were constipation, decreased appetite, rash, hemorrhage, increased weight, and hypertension. The most common laboratory test abnormalities (≥30%) were anemia, hyperglycemia, decreased lymphocyte count, decreased neutrophil count, increased AST, increased ALT, and hypocalcemia. Clinically relevant adverse reactions in <10% of patients who received NUBEQA with docetaxel included fractures, ischemic heart disease, seizures, and drug-induced liver injury.

Drug Interactions

Effect of Other Drugs on NUBEQA – Combined P-gp and strong or moderate CYP3A4 inducers decrease NUBEQA exposure, which may decrease NUBEQA activity. Avoid concomitant use.

Combined P-gp and strong CYP3A4 inhibitors increase NUBEQA exposure, which may increase the risk of NUBEQA adverse reactions. Monitor more frequently and modify NUBEQA dose as needed.

Effects of NUBEQA on Other Drugs – NUBEQA inhibits breast cancer resistance protein (BCRP) transporter. Concomitant use increases exposure (AUC) and maximal concentration of BCRP substrates, which may increase the risk of BCRP substrate-related toxicities. Avoid concomitant use where possible. If used together, monitor more frequently for adverse reactions, and consider dose reduction of the BCRP substrate.

NUBEQA inhibits OATP1B1 and OATP1B3 transporters. Concomitant use may increase plasma concentrations of OATP1B1 or OATP1B3 substrates. Monitor more frequently for adverse reactions and consider dose reduction of these substrates.

Review the Prescribing Information of drugs that are BCRP, OATP1B1, and OATP1B3 substrates when used concomitantly with NUBEQA.

For important risk and use information about NUBEQA, please see the accompanying full Prescribing Information.

About Xofigo (radium Ra 223 dichloride) Injection2

Xofigo is indicated for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease.

Important Safety Information for Xofigo (radium Ra 223 dichloride) Injection

Warnings and Precautions:

Bone Marrow Suppression: In the phase 3 ALSYMPCA trial, 2% of patients in the Xofigo arm experienced bone marrow failure or ongoing pancytopenia, compared to no patients treated with placebo. There were two deaths due to bone marrow failure. For 7 of 13 patients treated with Xofigo bone marrow failure was ongoing at the time of death. Among the 13 patients who experienced bone marrow failure, 54% required blood transfusions. Four percent (4%) of patients in the Xofigo arm and 2% in the placebo arm permanently discontinued therapy due to bone marrow suppression. In the randomized trial, deaths related to vascular hemorrhage in association with myelosuppression were observed in 1% of Xofigo-treated patients compared to 0.3% of patients treated with placebo. The incidence of infection-related deaths (2%), serious infections (10%), and febrile neutropenia (<1%) was similar for patients treated with Xofigo and placebo. Myelosuppression–notably thrombocytopenia, neutropenia, pancytopenia, and leukopenia–has been reported in patients treated with Xofigo.

Monitor patients with evidence of compromised bone marrow reserve closely and provide supportive care measures when clinically indicated. Discontinue Xofigo in patients who experience life-threatening complications despite supportive care for bone marrow failure
Hematological Evaluation: Monitor blood counts at baseline and prior to every dose of Xofigo. Prior to first administering Xofigo, the absolute neutrophil count (ANC) should be ≥1.5 × 109/L, the platelet count ≥100 × 109/L, and hemoglobin ≥10 g/dL. Prior to subsequent administrations, the ANC should be ≥1 × 109/L and the platelet count ≥50 × 109/L. Discontinue Xofigo if hematologic values do not recover within 6 to 8 weeks after the last administration despite receiving supportive care
Concomitant Use With Chemotherapy: Safety and efficacy of concomitant chemotherapy with Xofigo have not been established. Outside of a clinical trial, concomitant use of Xofigo in patients on chemotherapy is not recommended due to the potential for additive myelosuppression. If chemotherapy, other systemic radioisotopes, or hemibody external radiotherapy are administered during the treatment period, Xofigo should be discontinued
Increased Fractures and Mortality in Combination With Abiraterone Plus
Prednisone/Prednisolone: Xofigo is not recommended for use in combination with abiraterone acetate plus prednisone/prednisolone outside of clinical trials. At the primary analysis of the Phase 3 ERA-223 study that evaluated concurrent initiation of Xofigo in combination with abiraterone acetate plus prednisone/prednisolone in 806 asymptomatic or mildly symptomatic mCRPC patients, an increased incidence of fractures (28.6% vs 11.4%) and deaths (38.5% vs 35.5%) have been observed in patients who received Xofigo in combination with abiraterone acetate plus prednisone/prednisolone compared to patients who received placebo in combination with abiraterone acetate plus prednisone/prednisolone. Safety and efficacy with the combination of Xofigo and agents other than gonadotropin-releasing hormone analogues have not been established
Embryo-Fetal Toxicity: The safety and efficacy of Xofigo have not been established in females. Xofigo can cause fetal harm when administered to a pregnant female. Advise pregnant females and females of reproductive potential of the potential risk to a fetus. Advise male patients to use condoms and their female partners of reproductive potential to use effective contraception during and for 6 months after completing treatment with Xofigo
Administration and Radiation Protection: Xofigo should be received, used, and administered only by authorized persons in designated clinical settings. The administration of Xofigo is associated with potential risks to other persons from radiation or contamination from spills of bodily fluids such as urine, feces, or vomit. Therefore, radiation protection precautions must be taken in accordance with national and local regulations

Fluid Status: Dehydration occurred in 3% of patients on Xofigo and 1% of patients on placebo. Xofigo increases adverse reactions such as diarrhea, nausea, and vomiting, which may result in dehydration. Monitor patients’ oral intake and fluid status carefully and promptly treat patients who display signs or symptoms of dehydration or hypovolemia

Injection Site Reactions: Erythema, pain, and edema at the injection site were reported in 1% of patients on Xofigo

Secondary Malignant Neoplasms: Xofigo contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure may be associated with an increased risk of cancer and hereditary defects. Due to its mechanism of action and neoplastic changes, including osteosarcomas, in rats following administration of radium-223 dichloride, Xofigo may increase the risk of osteosarcoma or other secondary malignant neoplasms. However, the overall incidence of new malignancies in the randomized trial was lower on the Xofigo arm compared to placebo (<1% vs 2%; respectively), but the expected latency period for the development of secondary malignancies exceeds the duration of follow-up for patients on the trial

Subsequent Treatment With Cytotoxic Chemotherapy: In the randomized clinical trial, 16% of patients in the Xofigo group and 18% of patients in the placebo group received cytotoxic chemotherapy after completion of study treatments. Adequate safety monitoring and laboratory testing was not performed to assess how patients treated with Xofigo will tolerate subsequent cytotoxic chemotherapy

Adverse Reactions: The most common adverse reactions (≥10%) in the Xofigo arm vs the placebo arm, respectively, were nausea (36% vs 35%), diarrhea (25% vs 15%), vomiting (19% vs 14%), and peripheral edema (13% vs 10%). Grade 3 and 4 adverse events were reported in 57% of Xofigo-treated patients and 63% of placebo-treated patients. The most common hematologic laboratory abnormalities in the Xofigo arm (≥10%) vs the placebo arm, respectively, were anemia (93% vs 88%), lymphocytopenia (72% vs 53%), leukopenia (35% vs 10%), thrombocytopenia (31% vs 22%), and neutropenia (18% vs 5%)

Please see the full Prescribing Information for Xofigo (radium Ra 223 dichloride).

About Vitrakvi (larotrectinib)3

Vitrakvi (larotrectinib) is indicated for the treatment of adult and pediatric patients with solid tumors that have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection will likely result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment.

Select patients for therapy based on an FDA-approved test.

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Important Safety Information for Vitrakvi (larotrectinib)

Warnings and Precautions

Central Nervous System Effects: Central nervous system (CNS) adverse reactions occurred in patients receiving VITRAKVI, including dizziness, cognitive impairment, mood disorders, and sleep disturbances.

In patients who received VITRAKVI, all grades CNS effects including cognitive impairment, mood disorders, dizziness and sleep disorders were observed in 42% with Grades 3-4 in 3.9% of patients.

Cognitive impairment occurred in 11% of patients. The median time to onset of cognitive impairment was 5.6 months (range: 2 days to 41 months). Cognitive impairment occurring in ≥ 1% of patients included memory impairment (3.6%), confusional state (2.9%), disturbance in attention (2.9%), delirium (2.2%), cognitive disorders (1.4%), and Grade 3 cognitive adverse reactions occurred in 2.5% of patients. Among the 30 patients with cognitive impairment, 7% required a dose modification and 20% required dose interruption.

Mood disorders occurred in 14% of patients. The median time to onset of mood disorders was 3.9 months (range: 1 day to 40.5 months). Mood disorders occurring in ≥1% of patients included anxiety (5%), depression (3.9%), agitation (2.9%), and irritability (2.9%). Grade 3 mood disorders occurred in 0.4% of patients.

Dizziness occurred in 27% of patients, and Grade 3 dizziness occurred in 1.1% of patients. Among the 74 patients who experienced dizziness, 5% of patients required a dose modification and 5% required dose interruption.

Sleep disturbances occurred in 10% of patients. Sleep disturbances included insomnia (7%), somnolence (2.5%), and sleep disorder (0.4%). There were no Grade 3-4 sleep disturbances. Among the 28 patients who experienced sleep disturbances, 1 patient each (3.6%) required a dose modification or dose interruption.

Advise patients and caretakers of these risks with VITRAKVI. Advise patients not to drive or operate hazardous machinery if they are experiencing neurologic adverse reactions. Withhold or permanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVI dosage when resumed.
Skeletal Fractures: Among 187 adult patients who received VITRAKVI across clinical trials, fractures were reported in 7% and among 92 pediatric patients, fractures were reported in 9% (N=279; 8%). Median time to fracture was 11.6 months (range 0.9 to 45.8 months) in patients followed per fracture. Fractures of the femur, hip or acetabulum were reported in 4 patients (3 adult, 1 pediatric). Most fractures were associated with minimal or moderate trauma. Some fractures were associated with radiologic abnormalities suggestive of local tumor involvement. VITRAKVI treatment was interrupted due to fracture in 1.4% patients.

Promptly evaluate patients with signs or symptoms of potential fracture (e.g., pain, changes in mobility, deformity). There are no data on the effects of VITRAKVI on healing of known fractures or risk of future fractures.
Hepatotoxicity: In patients who received VITRAKVI, increased AST of any grade occurred in 52% of patients and increased ALT of any grade occurred in 45%. Grade 3-4 increased AST or ALT occurred in 3.1% and 2.5% of patients, respectively. The median time to onset of increased AST was 2.1 months (range: 1 day to 4.3 years). The median time to onset of increased ALT was 2.3 months (range: 1 day to 4.2 years). Increased AST and ALT leading to dose modifications occurred in 1.4% and 2.2% of patients, respectively. Increased AST or ALT led to permanent discontinuation in 3 (1.1%) patients.

Monitor liver tests, including ALT and AST, every 2 weeks during the first month of treatment, then monthly thereafter, and as clinically indicated. Withhold or permanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVI dosage when resumed.
Embryo-Fetal Toxicity: VITRAKVI can cause fetal harm when administered to a pregnant woman. VITRAKVI resulted in malformations in rats and rabbits at maternal exposures that were approximately 11- and 0.7-times, respectively, those observed at the clinical dose of 100 mg twice daily. Advise women of the potential risk to a fetus. Advise females of reproductive potential to use an effective method of contraception during treatment and for 1 week after the final dose of VITRAKVI.
Adverse Reactions

The most common adverse reactions (≥20%), including laboratory abnormalities, were: increased AST (52%), increased ALT (45%), anemia (42%), musculoskeletal pain (42%), fatigue (36%), hypoalbuminemia (36%), neutropenia (36%), increased alkaline phosphatase (34%), cough (32%), leukopenia (28%), constipation (27%), diarrhea (27%), dizziness (27%), hypocalcemia (25%), nausea (25%), vomiting (25%), pyrexia (24%), lymphopenia (22%) and abdominal pain (21%).
Drug Interactions

Avoid coadministration of VITRAKVI with strong CYP3A4 inhibitors (including grapefruit or grapefruit juice), strong CYP3A4 inducers (including St. John’s wort), or sensitive CYP3A4 substrates. If coadministration of strong CYP3A4 inhibitors or inducers cannot be avoided, modify the VITRAKVI dose as recommended. If coadministration of sensitive CYP3A4 substrates cannot be avoided, monitor patients for increased adverse reactions of these drugs. For coadministration with moderate CYP3A4 inhibitors, monitor for adverse reactions more frequently and reduce the dosage based on severity. For coadministration with moderate CYP3A4 inducers, modify dose as recommended.
Use in Specific Populations

Lactation: Advise women not to breastfeed during treatment with VITRAKVI and for 1 week after the final dose.
Please see the full Prescribing Information for VITRAKVI (larotrectinib).

About Aliqopa (copanlisib) Injection4

ALIQOPA (copanlisib) is indicated for the treatment of adult patients with relapsed follicular lymphoma (FL) who have received at least two prior systemic therapies. Accelerated approval was granted for this indication based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Aliqopa is an inhibitor of phosphatidylinositol-3-kinase (PI3K) with inhibitory activity predominantly against PI3K-α and PI3K-δ isoforms expressed in malignant B cells. Aliqopa has been shown to induce tumor cell death by apoptosis and inhibition of proliferation of primary malignant B cell lines. Aliqopa inhibits several key cell-signaling pathways, including B-cell receptor signaling, CXCR12 mediated chemotaxis of malignant B cells, and NFκB signaling in lymphoma cell lines.

The clinical development program for Aliqopa also includes the Phase III study CHRONOS-4, evaluating Aliqopa in combination with standard immunochemotherapy in relapsed iNHL. More information about this trial can be found at www.clinicaltrials.gov.

IMPORTANT SAFETY INFORMATION FOR ALIQOPA (copanlisib)

Infections: Serious, including fatal, infections occurred in 19% of 317 patients treated with ALIQOPA monotherapy. The most common serious infection was pneumonia. Monitor patients for signs and symptoms of infection and withhold ALIQOPA for Grade 3 and higher infection.

Serious pneumocystis jiroveci pneumonia (PJP) infection occurred in 0.6% of 317 patients treated with ALIQOPA monotherapy. Before initiating treatment with ALIQOPA, consider PJP prophylaxis for populations at risk. Withhold ALIQOPA in patients with suspected PJP infection of any grade. If confirmed, treat infection until resolution, then resume ALIQOPA at previous dose with concomitant PJP prophylaxis.

Hyperglycemia: Grade 3 or 4 hyperglycemia (blood glucose 250 mg/dL or greater) occurred in 41% of 317 patients treated with ALIQOPA monotherapy. Serious hyperglycemic events occurred in 2.8% of patients. Treatment with ALIQOPA may result in infusion-related hyperglycemia. Blood glucose levels typically peaked 5 to 8 hours post-infusion and subsequently declined to baseline levels for a majority of patients; blood glucose levels remained elevated in 17.7% of patients one day after ALIQOPA infusion. Of 155 patients with baseline HbA1c 6.5% at the end of treatment.

Of the twenty patients with diabetes mellitus treated in CHRONOS-1, seven developed Grade 4 hyperglycemia and two discontinued treatment. Patients with diabetes mellitus should only be treated with ALIQOPA following adequate glucose control and should be monitored closely.

Achieve optimal blood glucose control before starting each ALIQOPA infusion. Withhold, reduce dose, or discontinue ALIQOPA depending on the severity and persistence of hyperglycemia.

Hypertension: Grade 3 hypertension (systolic 160 mmHg or greater or diastolic 100 mmHg or greater) occurred in 26% of 317 patients treated with ALIQOPA monotherapy. Serious hypertensive events occurred in 0.9% of 317 patients. Treatment with ALIQOPA may result in infusion-related hypertension. The mean change of systolic and diastolic BP from baseline to 2 hours post-infusion on Cycle 1 Day 1 was 16.8 mmHg and 7.8 mmHg, respectively. The mean BP started decreasing approximately 2 hours post-infusion; BP remained elevated for 6 to 8 hours after the start of the ALIQOPA infusion. Optimal BP control should be achieved before starting each ALIQOPA infusion. Monitor BP pre- and post-infusion. Withhold, reduce dose, or discontinue ALIQOPA depending on the severity and persistence of hypertension.

Non-infectious Pneumonitis: Non-infectious pneumonitis occurred in 5% of 317 patients treated with ALIQOPA monotherapy. Withhold ALIQOPA and conduct a diagnostic examination of a patient who is experiencing pulmonary symptoms such as cough, dyspnea, hypoxia, or interstitial infiltrates on radiologic exam. Patients with pneumonitis thought to be caused by ALIQOPA have been managed by withholding ALIQOPA and administration of systemic corticosteroids. Withhold, reduce dose, or discontinue ALIQOPA depending on the severity and persistence of non-infectious pneumonitis.

Neutropenia: Grade 3 or 4 neutropenia occurred in 24% of 317 patients treated with ALIQOPA monotherapy. Serious neutropenic events occurred in 1.3%. Monitor blood counts at least weekly during treatment with ALIQOPA. Withhold, reduce dose, or discontinue ALIQOPA depending on the severity and persistence of neutropenia.

Severe Cutaneous Reaction: Grade 3 and 4 cutaneous reactions occurred in 2.8% and 0.6% of 317 patients treated with ALIQOPA monotherapy respectively. Serious cutaneous reaction events were reported in 0.9%. The reported events included dermatitis exfoliative, exfoliative rash, pruritus, and rash (including maculo-papular rash). Withhold, reduce dose, or discontinue ALIQOPA depending on the severity and persistence of severe cutaneous reactions.

Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, ALIQOPA can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of copanlisib to pregnant rats during organogenesis caused embryo-fetal death and fetal abnormalities in rats at maternal doses as low as 0.75 mg/kg/day (4.5 mg/m2 /day body surface area) corresponding to approximately 12% the recommended dose for patients. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for one month after the last dose.

Adverse Drug Reactions: Serious adverse reactions were reported in 44 (26%) patients. The most frequent serious adverse reactions that occurred were pneumonia (8%), pneumonitis (5%) and hyperglycemia (5%). Adverse reactions resulted in dose reduction in 36 (21%) and discontinuation in 27 (16%) patients. The most frequently observed adverse drug reactions (≥20%) in ALIQOPA-treated patients were: hyperglycemia (54%), leukopenia (36%), diarrhea (36%), decreased general strength and energy (36%), hypertension (35%), neutropenia (32%), nausea (26%), thrombocytopenia (22%), and lower respiratory tract infections (21%).

Drug Interactions: Avoid concomitant use with strong CYP3A inducers. Reduce the ALIQOPA dose to 45 mg when concomitantly administered with strong CYP3A inhibitors.

Lactation: Advise women not to breastfeed. Advise a lactating woman not to breastfeed during treatment with ALIQOPA and for one month after the last dose.

For important risk and use information about Aliqopa, please see the full Prescribing Information.

On May 25, 2023 Affini-T Therapeutics, Inc., a precision immunotherapy company unlocking the power of T cells against oncogenic driver mutations, reported that preclinical data for its oncogenic driver program targeting KRAS G12V, AFNT–211, will be presented at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, held in Chicago, June 2-6 (Press release, Affini-T Therapeutics, MAY 25, 2023, View Source [SID1234632121]).

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"We are pleased to present novel preclinical data from our cell therapy targeting KRAS G12V, highlighting the robust stemness properties of our cell product as a key aspect of its comprehensive characterization. These findings establish a solid research foundation and support our ongoing effort to advance the program as a potential paradigm-shifting treatment for solid tumors," said Loïc Vincent, Ph.D., Chief Scientific Officer, Affini-T Therapeutics. "Along with our collaborators, we will continue to push forward treatments targeting oncogenic driver mutations and look forward to presenting these findings at ASCO (Free ASCO Whitepaper) in Chicago."

Poster presentation details are as follows:

Developmental Therapeutics—Immunotherapy, Hall A, Abstract: 2543, Poster Board: 385, June 3 at 8 am CT / 9 am ET: AFNT-211: A FAS-41BB–enhanced TCR-T cell therapy with stem-like properties targeting KRAS G12V-expressing solid tumors – Presenting Authors: Thomas Schmitt, Ph.D., Fred Hutchinson Cancer Center and Scientific Co-Founder, Affini-T Therapeutics and Hue Lam, Ph.D., Vice President, Preclinical Development, Affini-T Therapeutics
"With the THRIVE T cell manufacturing platform, we can generate high yields of drug product exhibiting naïve and central memory phenotypes, enhancing the activity of this therapy," said Kim Nguyen, Ph.D., Chief Technical Officer, Affini-T Therapeutics. "Our IND-enabling studies have demonstrated potent and specific pharmacological action with a rigorous toxicology profile that support the advancement of the AFNT-211 program to the clinic."

On May 25, 2023 Pfizer Inc. (NYSE: PFE) reported that it will present data across its Oncology portfolio and growing pipeline, covering multiple tumor types and novel mechanisms of action at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago from June 2 through June 6 (Press release, Pfizer, MAY 25, 2023, View Source [SID1234632120]). Abstracts include new data from pivotal trials supporting ongoing regulatory reviews for three potential therapies, if approved, and new clinical data for six early pipeline assets. In addition, Pfizer will highlight its ongoing scientific leadership in breast cancer with additional real-world evidence (RWE) for IBRANCE (palbociclib) and initial first-in-human results for its novel CDK4- and CDK2-selective inhibitors, respectively, and novel epigenetic modulator KAT6 inhibitor.

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Discover why more than 1,500 members use 1stOncology™ to excel in:

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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"Forward-Looking Information and Factors That May Affect Future Results"

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"At ASCO (Free ASCO Whitepaper), Pfizer will present new data across the four key areas of our industry-leading portfolio – breast cancer, genitourinary cancer, hematology, and precision medicine – and for the first time, first-in-human data for some of our most exciting pipeline medicines," said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology and Rare Disease, Pfizer Global Product Development. "With four anticipated regulatory decisions this year and a growing portfolio of multiple mechanisms of action, Pfizer Oncology is poised to take our scientific innovation to the next level and bring new hope to people with cancer."

Today, Pfizer Oncology has a comprehensive portfolio of 24 approved innovative cancer medicines and biosimilars to treat more than 30 cancer types and an extensive pipeline of more than 30 programs in clinical development. With the recently announced proposed acquisition of Seagen*, a leader in antibody-drug conjugate technology, Pfizer is further accelerating its fight against cancer to deliver the next generation of Oncology breakthroughs.

"Placing patients at the center of everything we do is a critical component of advancing cutting-edge science and improving outcomes for patients," said Dany Habr, M.D., Oncology Chief Medical Affairs Officer, Pfizer. "At ASCO (Free ASCO Whitepaper), we look forward to connecting with the entire Oncology community to continue our efforts and shared approaches in making scientific breakthroughs accessible to all people living with cancer, everywhere."

Pfizer’s commitment to advancing scientific innovation will be on display at ASCO (Free ASCO Whitepaper) 2023 with more than 40 company-sponsored abstracts. Highlights include:

13 abstracts across the comprehensive MagnetisMM clinical trial program reinforcing the efficacy and safety of elranatamab, an investigational subcutaneous B-cell maturation antigen (BCMA)-CD3-targeted bispecific antibody, in relapsed or refractory multiple myeloma (RRMM), including an oral presentation on the first data from patients treated with prior BCMA-targeted therapy. Elranatamab is under Priority Review with the U.S. Food and Drug Administration (FDA) and under review with the European Medicines Agency (EMA) for the treatment of RRMM.
Four abstracts, including an oral presentation on new additional data from the Phase 3 TALAPRO-2 study, supporting the potential of TALZENNA (talazoparib), an oral poly ADP-ribose polymerase (PARP) inhibitor that plays a role in DNA damage repair, in combination with XTANDI (enzalutamide), an androgen receptor signaling inhibitor, in men with metastatic castration-resistant prostate cancer. The FDA has granted Priority Review for the Supplemental New Drug Application (sNDA) for TALZENNA in combination with XTANDI and an application is also under review with the EMA.
For the first time, the primary efficacy and safety results from the Phase 2 PHAROS trial exploring BRAFTOVI (encorafenib), an oral BRAF kinase inhibitor, given in combination with MEKTOVI (binimetinib), an oral MEK inhibitor, in patients with metastatic non-small cell lung cancer harboring a BRAF V600E mutation.** Results from the PHAROS study support the sNDAs for BRAFTOVI and MEKTOVI in this setting that are currently under review by the FDA.
Advancements across Pfizer’s leading breast cancer portfolio and pipeline, including a new analysis of real-world evidence for IBRANCE, an oral first-in-class inhibitor of cyclin-dependent kinases (CDKs) 4 and 6, as a first-line treatment of metastatic breast cancer. In addition, the first Phase 1 data for the CDK4-selective inhibitor PF-07220060, the CDK2-selective inhibitor PF-07104091 and the KAT6 inhibitor PF-07248144, all investigational agents for advanced or metastatic hormone-receptor positive breast cancer, will be presented.

A complete list of Pfizer-sponsored accepted abstracts is available at View Source

Pfizer is also continuing its commitment to help non-scientists understand the latest findings with the development of abstract plain language summaries (APLS) for company-sponsored research being presented at ASCO (Free ASCO Whitepaper), which are written in non-technical language. Those interested in learning more can visit www.Pfizer.com/apls to access the summaries starting May 25.

Key Pfizer-sponsored oral and poster discussion presentations at ASCO (Free ASCO Whitepaper) 2023 include:

BREAST CANCER

Poster Discussion (Abstract 3009)

Saturday, June 3, 1:15-2:45 PM CDT

First-in-human first-in-class Phase 1/2a study of the next generation CDK4-selective inhibitor PF-07220060 in patients (pts) with advanced solid tumors, enriched for HR+ HER2- mBC pts who progressed on prior CDK4/6 inhibitors and endocrine therapy.

Yap TA

Poster Discussion (Abstract 3010)

Saturday, June 3, 1:15-2:45 PM CDT

First-in-human Phase 1/2a study of a potent and novel CDK2-selective inhibitor PF-07104091 in patients (pts) with advanced solid tumors, enriched for CDK4/6 inhibitor resistant HR+/HER2- breast cancer pts.

Yap TA

Poster Discussion (Abstract 1018)

Sunday, June 4, 11:30 AM-1:00 PM CDT

First-line systemic treatment with palbociclib in women aged ≥70 years presenting with hormone receptors-positive advanced breast cancer: Results from the PALOMAGE program.

Carola E

GENITOURINARY CANCERS

Oral Presentation (Abstract 5004)

Sunday, June 4, 8:00-11:00 AM CDT

TALAPRO-2: Phase 3 study of talazoparib (TALA) + enzalutamide (ENZA) versus placebo (PBO) + ENZA as first-line (1L) treatment for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) harboring homologous recombination repair (HRR) gene alterations.

Agarwal N

Poster Discussion (Abstract 5013)

Saturday, June 3, 1:15-2:45 PM CDT

Patient-reported outcomes (PROs) among men receiving talazoparib (TALA) + enzalutamide (ENZA) vs placebo (PBO) + ENZA as first-line (1L) treatment for metastatic castration-resistant prostate cancer (mCRPC): Results from a phase 3 study (TALAPRO-2).

Agarwal N

Poster Discussion (Abstract 4515)

Saturday, June 3, 3:00-4:30 PM CDT

Estimated net benefit of avelumab (AVE) + best supportive care (BSC) vs BSC alone for patients (pts) with advanced urothelial carcinoma (aUC) using a quality-adjusted time without cancer symptoms or toxicity (Q-TWiST) analysis.

Powles T

Poster Discussion (Abstract 4516)

Saturday, June 3, 3:00-4:30 PM CDT

Long-term safety of avelumab first-line (1L) maintenance for advanced urothelial carcinoma (aUC) in the JAVELIN Bladder 100 trial.

Bellmunt J

HEMATOLOGY

Oral Presentation (Abstract 8008)

Saturday, June 3, 1:15-4:15 PM CDT

Efficacy and safety of elranatamab in patients with relapsed/refractory multiple myeloma (RRMM) and prior B-cell maturation antigen (BCMA)-directed therapies: A pooled analysis from MagnetisMM studies.

Nooka AK

PRECISION MEDICINE

Poster Discussion (Abstract 9018)

Sunday, June 4, 4:30-6:00 PM CDT

Efficacy and safety of encorafenib (enco) plus binimetinib (bini) in patients with BRAF V600E-mutant (BRAFV600E) metastatic non-small cell lung cancer (NSCLC) from the phase 2 PHAROS study.

Riely G

Other/Advanced Cancers

Oral Presentation (Abstract 11508)

Monday, June 5, 11:30 AM-2:30 PM CDT

Safety and clinical activity of TTI-621 in combination with doxorubicin in patients with unresectable or metastatic high-grade leiomyosarcoma: Results from the low-dose expansion cohort.

Movva S

Poster Discussion (Abstract 3020)

Saturday, June 3, 1:15-2:45 PM CDT

A first-in-human, phase 1 study of the SHP2 inhibitor PF-07284892 as monotherapy and in combination with different targeted therapies in oncogene-driven treatment-resistant solid tumors.

Drilon A

On May 25, 2023 Pionyr Immunotherapeutics, Inc., a company developing first-in-class Myeloid Tuning antibody therapeutics that enhance the body’s antitumor immunity by altering, or "tuning," immune cells within the tumor microenvironment, reported that PY159, a monoclonal antibody targeting TREM1 (triggering receptor expressed on macrophages 1), was well-tolerated with signals of durable therapeutic activity in a Phase 1a dose-escalation study as a single agent and in combination with pembrolizumab (Press release, Pionyr Immunotherapeutics, MAY 25, 2023, View Source [SID1234632119]). In 37 evaluable patients, two demonstrated partial responses and nine showed stable disease. A recommended dose of 3 mg/kg of PY159 has been determined, and seven expansion cohorts in prespecified indications are currently enrolling in the Phase 1b portion of the study. The study will be featured in a poster discussion session at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, held June 2-6 in Chicago and virtually.

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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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"PY159 is designed to activate the signaling of TREM1, which reprograms tumor-associated myeloid cells to stimulate anti-tumor immunity," said Leonard Reyno, President, R&D and Chief Medical Officer of Pionyr Immunotherapeutics. "The radiographic response data provide encouraging signals of efficacy, which is exciting given the novel Myeloid Tuning approach we are pursuing. This response combined with acceptable safety and tolerability both as a monotherapy and in combination with checkpoint inhibitor demonstrate the potential of this approach for treating solid tumors."

Safety and Tolerability as a Monotherapy and in Combination with Pembrolizumab Support Additional Clinical Studies

The Phase 1a dose-escalation study of PY159 was a non-randomized, open-label study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PY159 as a single agent and in combination with checkpoint inhibitor pembrolizumab in 37 subjects with advanced solid tumors. Dosing was intravenous and administered once every three weeks. Seven predefined dose levels of PY159 were delivered as a single agent, and four dose levels of PY159 were delivered in combination with pembrolizumab. No clinically relevant neutropenia was observed. The most common treatment-related adverse events were infusion-related reactions, arthralgia, fatigue, myalgia, and stomatitis, which were primarily Grade 1 or 2; however, one subject experienced a dose-limiting toxicity of asymptomatic Grade 3 transaminitis.

Early Radiographic Response Data Support Additional Clinical Studies

Out of the 37 evaluable subjects, the best radiographic response for clinical study participants was stable disease in nine subjects (25.7%: duration range 12-96+ weeks) and partial response in two subjects (5.7%, duration range 24-42 weeks). The two partial responses were in pancreatic and ovarian cancer. Dose expansion cohorts are currently enrolling in ovarian, breast (triple negative and HR+HER2-), colorectal, pancreatic, non-small cell lung, and head and neck cancers.

Poster Presentation at ASCO (Free ASCO Whitepaper) 2023

The poster titled, "A Phase 1a Dose Escalation Study of PY159, a Monoclonal Antibody Targeting TREM1, Triggering Receptor Expressed on Myeloid Cells 1," will be featured in a poster discussion session at the ASCO (Free ASCO Whitepaper) 2023 Annual Meeting at 3-4:30 pm CDT on June 3, 2023. The abstract is currently available on the ASCO (Free ASCO Whitepaper) 2023 website, and the poster will be available on the Pionyr company website here after the completion of the ASCO (Free ASCO Whitepaper) poster session.

About Myeloid Tuning

Pionyr has developed a therapeutic platform called Myeloid Tuning, a process that rebalances the tumor microenvironment (TME) to promote anti-tumor immunity. Myeloid cells are a type of immune cell and are part of a family of cell types that play an important role in both the activation and suppression of the immune response to cancer.

One such critical type of myeloid cell, tumor-associated macrophages (TAM), are a key component of the TME. TAMs are generally categorized into two functionally contrasting subtypes called M1-like and M2-like macrophages: M1-like typically exerts anti-tumor functions, including directly mediating antibody-dependent cell-mediated cytotoxicity (ADCC) to kill tumor cells; M2-like macrophages can promote the occurrence and metastasis of tumor cells, inhibit T cell-mediated anti-tumor immune response, promote tumor angiogenesis and lead to tumor progression.

Myeloid Tuning effectively describes the mechanism of introducing agents that shift the balance of inhibitory myeloid cells – including M2-like TAMs – towards more inflammatory M1-like TAMs to promote anti-tumor immune responses in the TME and destroy solid tumors.

About PY159

PY159 is an afucosylated humanized IgG1 monoclonal antibody that specifically binds human Triggering Receptor Expressed on Myeloid Cells 1 (TREM1). In preclinical studies, PY159 effectively induces signaling through the TREM1–DAP12 complex, leading to downstream phosphorylation, and an increase in production of cytokines and chemokines and the upregulation of costimulatory and activation markers. PY159 repolarizes intratumoral immunosuppressive myeloid cells, including M2-like anti-inflammatory tumor associated macrophages (TAMs), monocytes (monocytic myeloid derived suppressor cells, mMDSCs), and neutrophils (TANs) within the tumor microenvironment to become proinflammatory to promote anti-tumor immunity.

On May 25, 2023 EMD Serono, the Healthcare business of Merck KGaA, Darmstadt, Germany in the US and Canada, reported that 43 abstracts covering several modalities and mechanisms will be presented at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, June 2-6, Chicago (Press release, EMD Serono, MAY 25, 2023, View Source [SID1234632118]). New data for the medicines BAVENCIO (avelumab) and TEPMETKO (tepotinib) and pipeline assets including the first-in-class investigational IAP (inhibitor of apoptosis protein) inhibitor xevinapant demonstrate the Company’s efforts to pioneer novel medicines intended to improve the lives of people living with cancer.

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Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

"The research we will present at ASCO (Free ASCO Whitepaper) 2023 demonstrates that we are not only maximizing the impact of our standard-of-care treatments but also advancing development programs focused on synergistic approaches targeting key cancer pathways and mechanisms," said Victoria Zazulina, M.D., Head of Development Unit, Oncology, for the Healthcare business of Merck KGaA, Darmstadt, Germany.

Key presentations include:

BAVENCIO (Abstracts: 4515, 4516) clinical data reinforce its role as a standard of care in first-line maintenance for advanced urothelial carcinoma (UC): Poster discussions, including long-term safety analyses and an analysis of quality-adjusted survival from the Phase III JAVELIN Bladder 100 study, confirm the acceptable long-term benefit-risk profile as well as the net benefit estimate of BAVENCIO first-line (1L) maintenance and further support its use as a standard of care for advanced UC. As part of the JAVELIN Bladder regimen, BAVENCIO first-line maintenance has demonstrated the longest survival benefit seen to date in a global, randomized Phase III trial in advanced UC.
Xevinapant (Abstracts: TPS6101, 6027) preclinical data supporting dosing rationale for this investigational IAP inhibitor as well as a trial-in-progress poster outlining design of the recently initiated Phase III XRay Vision study in locally advanced squamous cell carcinoma of the head and neck (LA SCCHN): Preclinical data demonstrate the benefit of extended xevinapant treatment beyond the completion of xevinapant plus radiotherapy (RT) and support the rationale for administration of six cycles of xevinapant in the ongoing Phase III studies, while also indicating that restoring sensitivity to apoptosis may address some unmet treatment needs in LA SCCHN. The trial design of the ongoing randomized Phase III XRay Vision study also will be featured. This study is assessing xevinapant plus RT in patients with resected, high-risk LA SCCHN who are not eligible for cisplatin.
TEPMETKO (Abstracts: 9021, 9060, 9070, 9074) data continue to demonstrate durable efficacy for first-line treatment of METex14 advanced non-small cell lung cancer (NSCLC): Long-term outcomes from the VISION study, the largest study of a MET inhibitor in patients with METex14-skipping advanced NSCLC (N=313), demonstrate the robust and durable clinical activity of TEPMETKO, particularly in the first-line setting, detected by liquid and/or tissue biopsy: with median follow-up of 32.6 months, in 164 first-line patients, overall response rate was 57.3% (95% CI: 49.4, 65.0) and median duration of response was 46.4 months (13.8, not estimable). A manageable safety profile further supports its use in clinical practice. Additional presentations for TEPMETKO include analyses from the INSIGHT 2 study in EGFRm METamp NSCLC for patients treated with TEPMETKO plus osimertinib.
Additional company-sponsored activity at ASCO (Free ASCO Whitepaper):

CME Live Symposium & Webcast, "After More Than a Decade: Can We Now Enhance Treatment of Patients With LA SCCHN?" with course director Kevin Harrington, PhD, FRCR, FRCP, The Institute of Cancer Research, The Royal Marsden Hospital, London, UK, on June 3, 7:00-8:00 PM CDT, Hilton Chicago (720 South Michigan Ave.), room Continental A.
In addition to the data being presented at ASCO (Free ASCO Whitepaper) 2023, EMD Serono will launch a new educational initiative for oncology professionals on the unmet medical need in LA SCCHN, cancer’s resistance to apoptosis, and the role of apoptosis proteins. More information on the initiative can be found at www.TheWallinSCCHN.com.

Select EMD Serono-related abstracts accepted for presentation at ASCO (Free ASCO Whitepaper) 2023 include (all times in CDT):

Title

Lead Author

Abstract

Session Information

BAVENCIO (avelumab)

Advanced Urothelial Carcinoma

Long-term safety of avelumab first-line (1L) maintenance for advanced urothelial carcinoma (aUC) in the JAVELIN Bladder 100 trial

Bellmunt J

4516

Genitourinary Cancer: Kidney and Bladder

Saturday, June 3, 2023

8:00AM-11:00AM

Poster Discussion Time:

3:00PM-4:30PM

Estimated net benefit of avelumab (AVE) + best supportive care (BSC) vs BSC alone for patients (pts) with advanced urothelial carcinoma (aUC) using a quality-adjusted time without cancer symptoms or toxicity (Q-TWiST) analysis

Powles T

4515

Genitourinary Cancer: Kidney and Bladder

Saturday, June 3, 2023

8:00AM-11:00AM

Poster Discussion Time:

3:00PM-4:30PM

Real-world response (rwR) rates and clinical outcomes of patients treated with first-line (1L) platinum-based chemotherapy (PBC) for advanced urothelial cancer (aUC)

Moon HH

4567

Genitourinary Cancer: Kidney and Bladder

Saturday, June 3, 2023

8:00 AM-11:00 AM

Metastatic Merkel Cell Carcinoma

Avelumab as second-line or later (2L+) treatment in patients (pts) with metastatic Merkel cell carcinoma (mMCC): analysis of real-world outcomes in France using the CARADERM registry and the French national healthcare database

Blom A

9537

Melanoma/Skin Cancers

Saturday, June 3, 2023

1:15PM-4:15PM

Metastatic Colorectal Cancer

Modified FOLFOXIRI plus cetuximab and avelumab as initial therapy in RAS wild-type unresectable metastatic colorectal cancer: results of the phase II AVETRIC trial by GONO

Conca V

3575

Gastrointestinal Cancer: Colorectal and Anal

Monday, June 5, 2023

8:00AM-11:00AM

Xevinapant

Phase 3 study of xevinapant plus radiotherapy (RT) for high-risk, cisplatin-ineligible patients with resected, locally advanced squamous cell carcinoma of the head and neck (LA SCCHN)

Ferris RL

TPS6101

Head and Neck Cancer

Monday, June 5, 2023

1:15PM-4:15PM

Effect of extended treatment with IAP inhibitor xevinapant post radiotherapy (RT) on efficacy and the tumor microenvironment (TME) in preclinical models

Yeung TL

6027

Head and Neck Cancer

Monday, June 5, 2023

1:15PM-4:15PM

TEPMETKO (tepotinib)

Long-term outcomes of tepotinib in patients with MET exon 14 skipping NSCLC from the VISION study

Paik P

9060

Lung Cancer: Non-Small Cell Metastatic

Sunday, June 4, 2023

8:00AM-11:00AM

Tepotinib + osimertinib for EGFR mutant (EGFRm) NSCLC with MET amplification (METamp) after first-line (1L) osimertinib

Tan D

9021

Lung Cancer: Non-Small Cell Metastatic

Sunday, June 4, 2023

8:00AM-11:00AM

Poster Discussion Time:

4:30PM-6:00PM

Detection of MET amplification (METamp) in patients with EGFR mutant (m) NSCLC after first-line (1L) osimertinib

Yu H

9074

Lung Cancer: Non-Small Cell Metastatic

Sunday, June 4, 2023

8:00AM-11:00AM

Patients with EGFR-mutant (m) MET-altered NSCLC receiving tepotinib with an EGFR tyrosine kinase inhibitor (TKI): a case series

Le X

9070

Lung Cancer: Non-Small Cell Metastatic

Sunday, June 4, 2023

8:00 AM-11:00 AM

Advancing the Future of Cancer Care
At EMD Serono, we strive every day to improve the futures of people living with cancer. Our research explores the full potential of promising mechanisms in cancer research, focused on synergistic approaches designed to hit cancer at its core. We are determined to maximize the impact of our standard-of-care treatments and to continue pioneering novel medicines. Our vision is to create a world where more cancer patients will become cancer survivors. Learn more at www.emdseronooncology.com.

About BAVENCIO (avelumab)
BAVENCIO is a human anti-programmed death ligand-1 (PD-L1) antibody. BAVENCIO has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, BAVENCIO has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models. The Merck KGaA, Darmstadt, Germany-Pfizer strategic alliance regarding BAVENCIO was mutually terminated, with an effective date of June 30, 2023, with Merck KGaA, Darmstadt, Germany regaining exclusive worldwide rights for BAVENCIO.

BAVENCIO Approved Indications
BAVENCIO (avelumab) is indicated in the US for the maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) that has not progressed with first-line platinum-containing chemotherapy. BAVENCIO is also indicated for the treatment of patients with locally advanced or metastatic UC who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

BAVENCIO in combination with INLYTA (axitinib) is indicated in the US for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

In the US, the FDA granted accelerated approval for BAVENCIO for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.

BAVENCIO is currently approved for at least one indication for patients in more than 50 countries.

BAVENCIO Important Safety Information from the US FDA-Approved Label
BAVENCIO can cause severe and fatal immune-mediated adverse reactions in any organ system or tissue and at any time after starting treatment with a PD-1/PD-L1 blocking antibody, including after discontinuation of treatment.

Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. 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.

No dose reduction for BAVENCIO is recommended. For immune-mediated adverse reactions, withhold or permanently discontinue BAVENCIO depending on severity. In general, withhold BAVENCIO for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue BAVENCIO for life-threatening (Grade 4) immune-mediated adverse reactions, recurrent severe (Grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to 10 mg or less of prednisone or equivalent per day within 12 weeks of initiating corticosteroids. In general, if BAVENCIO 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 immune-mediated adverse reactions are not controlled with corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic corticosteroids (eg, endocrinopathies and dermatologic reactions) are discussed in subsequent sections.

BAVENCIO can cause immune-mediated pneumonitis, including fatal cases. Monitor patients for signs and symptoms of pneumonitis and evaluate suspected cases with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold BAVENCIO for Grade 2 and permanently discontinue for Grade 3 or Grade 4 pneumonitis. Immune-mediated pneumonitis occurred in 1.2% (21/1738) of patients, including fatal (0.1%), Grade 4 (0.1%), Grade 3 (0.3%) and Grade 2 (0.6%) adverse reactions. Systemic corticosteroids were required in all (21/21) patients with pneumonitis.

BAVENCIO can cause immune-mediated colitis. The primary component of immune-mediated colitis consisted of 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. Withhold BAVENCIO for Grade 2 or Grade 3, and permanently discontinue for Grade 4 colitis. Immune-mediated colitis occurred in 1.5% (26/1738) of patients, including Grade 3 (0.4%) and Grade 2 (0.7%) adverse reactions. Systemic corticosteroids were required in all (26/26) patients with colitis.

BAVENCIO can cause hepatotoxicity and immune-mediated hepatitis. Withhold or permanently discontinue BAVENCIO based on tumor involvement of the liver and severity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin elevation. Immune-mediated hepatitis occurred with BAVENCIO as a single agent in 0.9% (16/1738) of patients, including fatal (0.1%), Grade 3 (0.6%), and Grade 2 (0.1%) adverse reactions. Systemic corticosteroids were required in all (16/16) patients with hepatitis.

BAVENCIO in combination with INLYTA can cause hepatotoxicity with higher than expected frequencies of Grade 3 and 4 ALT and AST elevation compared to BAVENCIO alone. Consider more frequent monitoring of liver enzymes as compared to when the drugs are used as monotherapy. Withhold or permanently discontinue both BAVENCIO and INLYTA based on severity of AST, ALT, or total bilirubin elevation, and consider administering corticosteroids as needed. Consider rechallenge with BAVENCIO or INLYTA, or sequential rechallenge with both BAVENCIO and INLYTA, after recovery. In patients treated with BAVENCIO in combination with INLYTA in the advanced RCC trials, increased ALT and increased AST were reported in 9% (Grade 3) and 7% (Grade 4) of patients. Immune-mediated hepatitis was reported in 7% of patients including 4.9% with Grade 3 or 4 immune-mediated hepatitis. Thirty-four patients were treated with corticosteroids and one patient was treated with a non-steroidal immunosuppressant.

BAVENCIO can cause primary or secondary immune-mediated adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement, as clinically indicated. Withhold BAVENCIO for Grade 3 or Grade 4 endocrinopathies until clinically stable or permanently discontinue depending on severity. Immune-mediated adrenal insufficiency occurred in 0.5% (8/1738) of patients, including Grade 3 (0.1%) and Grade 2 (0.3%) adverse reactions. Systemic corticosteroids were required in all (8/8) patients with adrenal insufficiency.

BAVENCIO 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 clinically indicated. Withhold BAVENCIO for Grade 3 or Grade 4 endocrinopathies until clinically stable or permanently discontinue depending on severity. Immune-mediated pituitary disorders occurred in 0.1% (1/1738) of patients, which was a Grade 2 (0.1%) adverse reaction.

BAVENCIO 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 BAVENCIO for Grade 3 or Grade 4 endocrinopathies until clinically stable or permanently discontinue depending on severity. Thyroiditis occurred in 0.2% (4/1738) of patients, including Grade 2 (0.1%) adverse reactions. Hyperthyroidism occurred in 0.4% (7/1738) of patients, including Grade 2 (0.3%) adverse reactions. Systemic corticosteroids were required in 29% (2/7) of patients with hyperthyroidism. Hypothyroidism occurred in 5% (90/1738) of patients, including Grade 3 (0.2%) and Grade 2 (3.7%) adverse reactions. Systemic corticosteroids were required in 7% (6/90) of patients with hypothyroidism.

BAVENCIO can cause immune-mediated type I diabetes mellitus, 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 BAVENCIO for Grade 3 or Grade 4 endocrinopathies until clinically stable or permanently discontinue depending on severity. Immune-mediated type I diabetes mellitus occurred in 0.1% (2/1738) of patients, including Grade 3 (0.1%) adverse reactions.

BAVENCIO can cause immune-mediated nephritis with renal dysfunction. Withhold BAVENCIO for Grade 2 or Grade 3, and permanently discontinue for Grade 4 increased blood creatinine. Immune-mediated nephritis with renal dysfunction occurred in 0.1% (1/1738) of patients, which was a Grade 2 (0.1%) adverse reaction. Systemic corticosteroids were required in this patient.

BAVENCIO can cause immune-mediated dermatologic adverse reactions, including rash or dermatitis. Exfoliative dermatitis including Stevens Johnson Syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), has occurred with PD-1/PD-L1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Withhold BAVENCIO for suspected and permanently discontinue for confirmed SJS, TEN, or DRESS. Immune-mediated dermatologic adverse reactions occurred in 5% (90/1738) of patients, including Grade 3 (0.1%) and Grade 2 (2.0%) adverse reactions. Systemic corticosteroids were required in 29% (26/90) of patients with dermatologic adverse reactions.

BAVENCIO can result in other immune-mediated adverse reactions. Other clinically significant immune-mediated adverse reactions occurred at an incidence of <1% in patients who received BAVENCIO or were reported with the use of other PD-1/PD-L1 blocking antibodies. For myocarditis, permanently discontinue BAVENCIO for Grade 2, Grade 3, or Grade 4. For neurological toxicities, withhold BAVENCIO for Grade 2 and permanently discontinue for Grade 3 or Grade 4.

BAVENCIO can cause severe or life-threatening infusion-related reactions. Premedicate patients with an antihistamine and acetaminophen prior to the first 4 infusions and for subsequent infusions based upon clinical judgment and presence/severity of prior infusion reactions. Monitor patients for signs and symptoms of infusion-related reactions, including pyrexia, chills, flushing, hypotension, dyspnea, wheezing, back pain, abdominal pain, and urticaria. Interrupt or slow the rate of infusion for Grade 1 or Grade 2 infusion-related reactions. Permanently discontinue BAVENCIO for Grade 3 or Grade 4 infusion-related reactions. Infusion-related reactions occurred in 25% of patients, including three (0.2%) Grade 4 and nine (0.5%) Grade 3 infusion-related reactions. Eleven (92%) of the 12 patients with Grade ≥3 reactions were treated with intravenous corticosteroids.

Fatal and other serious complications of allogeneic hematopoietic stem cell transplantation (HSCT) can occur in patients who receive HSCT before or after being treated with a PD-1/PD-L1 blocking antibody. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/PD-L1 blocking antibody prior to or after an allogeneic HSCT.

BAVENCIO in combination with INLYTA can cause major adverse cardiovascular events (MACE) including severe and fatal events. Consider baseline and periodic evaluations of left ventricular ejection fraction. Monitor for signs and symptoms of cardiovascular events. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Permanently discontinue BAVENCIO and INLYTA for Grade 3-4 cardiovascular events. MACE occurred in 7% of patients with advanced RCC treated with BAVENCIO in combination with INLYTA compared to 3.4% treated with sunitinib in a randomized trial. These events included death due to cardiac events (1.4%), Grade 3-4 myocardial infarction (2.8%), and Grade 3-4 congestive heart failure (1.8%).

BAVENCIO can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus including the risk of fetal death. Advise females of childbearing potential to use effective contraception during treatment with BAVENCIO and for at least 1 month after the last dose of BAVENCIO. It is not known whether BAVENCIO is excreted in human milk. Advise a lactating woman not to breastfeed during treatment and for at least 1 month after the last dose of BAVENCIO due to the potential for serious adverse reactions in breastfed infants.

The most common adverse reactions (all grades, ≥20%) in patients with metastatic Merkel cell carcinoma (MCC) were fatigue (50%), musculoskeletal pain (32%), diarrhea (23%), nausea (22%), infusion-related reaction (22%), rash (22%), decreased appetite (20%), and peripheral edema (20%).

Selected treatment-emergent laboratory abnormalities (all grades, ≥20%) in patients with metastatic MCC were lymphopenia (49%), anemia (35%), increased aspartate aminotransferase (34%), thrombocytopenia (27%), and increased alanine aminotransferase (20%).

A fatal adverse reaction (sepsis) occurred in one (0.3%) patient with locally advanced or metastatic urothelial carcinoma (UC) receiving BAVENCIO + best supportive care (BSC) as first-line maintenance treatment. In patients with previously treated locally advanced or metastatic UC, fourteen patients (6%) who were treated with BAVENCIO experienced either pneumonitis, respiratory failure, sepsis/urosepsis, cerebrovascular accident, or gastrointestinal adverse events, which led to death.

The most common adverse reactions (all grades, ≥20%) in patients with locally advanced or metastatic UC receiving BAVENCIO + BSC (vs BSC alone) as first-line maintenance treatment were fatigue (35% vs 13%), musculoskeletal pain (24% vs 15%), urinary tract infection (20% vs 11%), and rash (20% vs 2.3%). In patients with previously treated locally advanced or metastatic UC receiving BAVENCIO, the most common adverse reactions (all grades, ≥20%) were fatigue, infusion-related reaction, musculoskeletal pain, nausea, decreased appetite, and urinary tract infection.

Selected laboratory abnormalities (all grades, ≥20%) in patients with locally advanced or metastatic UC receiving BAVENCIO + BSC (vs BSC alone) as first-line maintenance treatment were blood triglycerides increased (34% vs 28%), alkaline phosphatase increased (30% vs 20%), blood sodium decreased (28% vs 20%), lipase increased (25% vs 16%), aspartate aminotransferase (AST) increased (24% vs 12%), blood potassium increased (24% vs 16%), alanine aminotransferase (ALT) increased (24% vs 12%), blood cholesterol increased (22% vs 16%), serum amylase increased (21% vs 12%), hemoglobin decreased (28% vs 18%), and white blood cell decreased (20% vs 10%).

Fatal adverse reactions occurred in 1.8% of patients with advanced renal cell carcinoma (RCC) receiving BAVENCIO in combination with INLYTA. These included sudden cardiac death (1.2%), stroke (0.2%), myocarditis (0.2%), and necrotizing pancreatitis (0.2%).

The most common adverse reactions (all grades, ≥20%) in patients with advanced RCC receiving BAVENCIO in combination with INLYTA (vs sunitinib) were diarrhea (62% vs 48%), fatigue (53% vs 54%), hypertension (50% vs 36%), musculoskeletal pain (40% vs 33%), nausea (34% vs 39%), mucositis (34% vs 35%), palmar-plantar erythrodysesthesia (33% vs 34%), dysphonia (31% vs 3.2%), decreased appetite (26% vs 29%), hypothyroidism (25% vs 14%), rash (25% vs 16%), hepatotoxicity (24% vs 18%), cough (23% vs 19%), dyspnea (23% vs 16%), abdominal pain (22% vs 19%), and headache (21% vs 16%).

Selected laboratory abnormalities (all grades, ≥20%) worsening from baseline in patients with advanced RCC receiving BAVENCIO in combination with INLYTA (vs sunitinib) were blood triglycerides increased (71% vs 48%), blood creatinine increased (62% vs 68%), blood cholesterol increased (57% vs 22%), alanine aminotransferase increased (ALT) (50% vs 46%), aspartate aminotransferase increased (AST) (47% vs 57%), blood sodium decreased (38% vs 37%), lipase increased (37% vs 25%), blood potassium increased (35% vs 28%), platelet count decreased (27% vs 80%), blood bilirubin increased (21% vs 23%), and hemoglobin decreased (21% vs 65%).

Please see full US Prescribing Information and Medication Guide available at View Source

About TEPMETKO (tepotinib)
TEPMETKO is a once-daily oral MET inhibitor that inhibits the oncogenic MET receptor signaling caused by MET (gene) alterations. Discovered and developed in-house at Merck KGaA, Darmstadt, Germany, TEPMETKO has a highly selective mechanism of action, with the potential to improve outcomes in aggressive tumors that have a poor prognosis and harbor these specific alterations.

TEPMETKO was the first oral MET inhibitor to receive a regulatory approval anywhere in the world for the treatment of advanced NSCLC harboring MET gene alterations, with its approval in Japan in March 2020. In February 2021, the US Food and Drug Administration granted accelerated approval to TEPMETKO, making it the first and only once-daily oral MET inhibitor approved for patients in the US with metastatic NSCLC with METex14-skipping alterations. In February 2022, the European Commission (EC) approved once-daily oral TEPMETKO as monotherapy for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) harboring alterations leading to mesenchymal-epithelial transition factor gene exon 14 (METex14) skipping, who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy.

TEPMETKO is available in a number of countries. To meet an urgent clinical need, TEPMETKO is also available in a pilot zone of China in line with the government policy to drive early access for innovative medicines approved outside of China.

Merck KGaA, Darmstadt, Germany is also investigating the potential role of tepotinib in treating patients with NSCLC and acquired resistance due to MET amplification in the Phase II INSIGHT 2 study of tepotinib in combination with osimertinib in MET amplified, advanced or metastatic NSCLC harboring activating EGFR mutations that has progressed following first-line treatment with osimertinib.

TEPMETKO Approved Indication in the US
TEPMETKO is a kinase inhibitor indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal epithelial transition (MET) exon 14 skipping alterations. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Important Safety Information from the US FDA-Approved Label
TEPMETKO can cause interstitial lung disease (ILD)/pneumonitis, which can be fatal. Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, fever). Immediately withhold TEPMETKO in patients with suspected ILD/pneumonitis and permanently discontinue if no other potential causes of ILD/pneumonitis are identified. ILD/pneumonitis occurred in 2.2% of patients treated with TEPMETKO, with one patient experiencing a Grade 3 or higher event; this event resulted in death.

TEPMETKO can cause hepatotoxicity, which can be fatal. Monitor liver function tests (including ALT, AST, and total bilirubin) prior to the start of TEPMETKO, every 2 weeks during the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop increased transaminases or total bilirubin. Based on the severity of the adverse reaction, withhold, dose reduce, or permanently discontinue TEPMETKO. Increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST) occurred in 13% of patients treated with TEPMETKO. Grade 3 or 4 increased ALT/AST occurred in 4.2% of patients. A fatal adverse reaction of hepatic failure occurred in one patient (0.2%). The median time-to-onset of Grade 3 or higher increased ALT/AST was 30 days (range 1 to 178).

TEPMETKO can cause embryo-fetal toxicity. Based on findings in animal studies and its mechanism of action, TEPMETKO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential or males with female partners of reproductive potential to use effective contraception during treatment with TEPMETKO and for one week after the final dose.

Avoid concomitant use of TEPMETKO with dual strong CYP3A inhibitors and P-gp inhibitors and strong CYP3A inducers. Avoid concomitant use of TEPMETKO with certain P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. If concomitant use is unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.

Fatal adverse reactions occurred in one patient (0.4%) due to pneumonitis, one patient (0.4%) due to hepatic failure, and one patient (0.4%) due to dyspnea from fluid overload.

Serious adverse reactions occurred in 45% of patients who received TEPMETKO. Serious adverse reactions in >2% of patients included pleural effusion (7%), pneumonia (5%), edema (3.9%), dyspnea (3.9%), general health deterioration (3.5%), pulmonary embolism (2%), and musculoskeletal pain (2%).

The most common adverse reactions (≥20%) in patients who received TEPMETKO were edema, fatigue, nausea, diarrhea, musculoskeletal pain, and dyspnea.

Clinically relevant adverse reactions in <10% of patients who received TEPMETKO included ILD/pneumonitis, rash, fever, dizziness, pruritus, and headache.

Selected laboratory abnormalities (≥20%) from baseline in patients receiving TEPMETKO in descending order were: decreased albumin (76%), increased creatinine (55%), increased alkaline phosphatase (ALP) (50%), decreased lymphocytes (48%), increased alanine aminotransferase (ALT) (44%), increased aspartate aminotransferase (AST) (35%), decreased sodium (31%), decreased hemoglobin (27%), increased potassium (25%), increased gamma-glutamyltransferase (GGT) (24%), increased amylase (23%), and decreased leukocytes (23%).

The most common Grade 3 to 4 laboratory abnormalities (≥2%) in descending order were: decreased lymphocytes (11%), decreased albumin (9%), decreased sodium (8%), increased GGT (5%), increased amylase (4.6%), increased ALT (4.1%), increased AST (2.5%), and decreased hemoglobin (2%).

A clinically relevant laboratory abnormality in <20% of patients who received TEPMETKO was increased lipase in 18% of patients, including 3.7% Grades 3 to 4.

For more information about TEPMETKO, please see full Prescribing Information, and visit www.TEPMETKO.com.

About Xevinapant
Xevinapant (formerly known as Debio 1143) is an investigational first-in-class potent oral small-molecule IAP (inhibitor of apoptosis protein) inhibitor for the treatment of LA SCCHN. In preclinical studies, xevinapant restored sensitivity to apoptosis in cancer cells, thereby enhancing the effects of chemotherapy and radiotherapy. Xevinapant, the most clinically advanced IAP inhibitor, improved efficacy outcomes in combination with chemoradiotherapy (CRT), including three-year progression-free survival and five-year survival, compared with placebo plus CRT in a Phase II study in patients with unresected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). In March 2021, Merck KGaA, Darmstadt, Germany, gained exclusive rights from Debiopharm to develop and commercialize xevinapant worldwide. Xevinapant is not approved for any use anywhere in the world.