On May 26, 2022 Biogen Inc. (Nasdaq: BIIB) reported that Michael McDonnell, Chief Financial Officer, and Priya Singhal, M.D., M.P.H., Head of Global Safety and Regulatory Sciences and Interim Head of R&D, will participate in the Jefferies Healthcare Conference (Press release, Biogen, MAY 26, 2022, View Source [SID1234615187]). The webcast will be live on Thursday, June 9, 2022, at 11:30 a.m. ET. To access the live webcast, please visit the Investors section of Biogen’s website at investors.biogen.com. An archived version of the webcast will be available following the presentation.

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On May 26, 2022 Bristol Myers Squibb (NYSE: BMY) reported results from the primary analysis of PILOT, a multicenter, Phase 2 study evaluating Breyanzi (lisocabtagene maraleucel) in adults with refractory or relapsed large B-cell lymphoma (LBCL) after first-line therapy who were not deemed candidates for high-dose chemotherapy and hematopoietic stem cell transplant (HSCT) (Press release, Bristol-Myers Squibb, MAY 26, 2022, View Source [SID1234615072]). The PILOT study is the only company-sponsored trial to evaluate a CAR T cell therapy as a second-line treatment for patients with relapsed or refractory LBCL who are not considered candidates for stem cell transplant. The data will be presented in a poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on Saturday, June 4 from 9:00 AM – 12:00 PM EDT (ABSTRACT 7062).

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The PILOT study enrolled a broad patient population of adults with refractory or relapsed LBCL after first-line treatment who were not considered candidates for transplant based on age, performance status and/or organ function and comorbidities, and regardless of time to relapse following first-line treatment. With a median follow-up of 12.3 months, the majority of patients treated with Breyanzi (n=61) saw a reduction in disease, with 80% of patients responding to treatment (overall response rate; 95% CI: 68.2 – 89.4) and 54% of patients achieving a complete response (CR; 95% CI:40.8-66.9). Responses with Breyanzi were durable, with a median duration of response of 12.1 months (95% CI: 6.2-NR) at 15.5 months median follow-up. In patients who achieved a CR, median duration of response was 21.7 months (95% CI: 12.7-NR). Median progression-free survival with Breyanzi was 9.0 months (95% CI: 4.2-NR), and median overall survival has not been reached (95% CI: 17.3-NR). In the PILOT study, patients were treated with Breyanzi and monitoredin both the inpatient and outpatient setting.

"For patients with large B-cell lymphoma that is refractory to or relapses after first-line therapy, stem cell transplant has been the only potentially curative treatment option, but the reality is many patients are not candidates for stem cell transplant, leaving limited treatment options," said Leo I. Gordon, M.D., study investigator, Professor in Medicine, Northwestern University Feinberg School of Medicine and the Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois. "The results from the PILOT study, including the patient-reported outcomes, show that treatment with liso-cel as a second-line therapy offers durable responses with improved quality of life for patients who historically have had poor prognosis."

LBCL, the most common type of non-Hodgkin lymphoma, is an aggressive blood cancer and approximately 40% of patients will have disease that is refractory to or relapses after first-line treatment. High-dose chemotherapy followed by autologous stem cell transplant has been the mainstay of care in the second-line setting; however, less than half of patients with primary refractory or relapsed disease are considered candidates for a stem cell transplant. For these patients, there are limited treatments that provide long-term disease control and palliative care is often the only option. If left untreated, patients with relapsed or refractory LBCL have a life expectancy of just three to four months.

"At Bristol Myers Squibb, we strive for cure by advancing innovative therapies that may provide long-term clinical benefit for some of the most challenging cancers with the hope of creating new standards of care that not only improve outcomes but also the patient experience," said Anne Kerber, senior vice president, Cell Therapy Development, Bristol Myers Squibb. "With Breyanzi, we have boldly designed a broad clinical trial program in relapsed or refractory LBCL, including patients who are not intended for stem cell transplant after failure of first-line therapy. These results from the PILOT study continue to demonstrate the practice-changing potential of Breyanzi in this setting, delivering on the promise of CAR T cell therapy for more patients."

In the PILOT study, Breyanzi showed a manageable safety profile with no new safety signals and low rates of severe cytokine release syndrome (CRS) or neurologic events, and no Grade 4/5 CRS or neurologic events reported. Any grade CRS occurred in 38% of patients, with Grade 3 CRS reported in one patient (2%). Any grade neurologic events were seen in 31% of patients with Grade 3 neurologic events reported in three patients (5%).

In a separate analysis of patient-reported outcomes (PRO) from the PILOT study, patients who received Breyanzi and were evaluable for the PRO analysis (n=56) showed significant improvements in fatigue and pain. Improvements in overall lymphoma symptoms were clinically meaningful following treatment with Breyanzi, and in an individual patient-level analysis, 70% of patients reported meaningful improvements in quality of life based on FACT-LymS scores at month 6. Results from the analysis will be presented in a poster presentation on Monday, June 6 from 2:15 PM – 5:15 PM EDT (Abstract 6567).

A supplemental Biologics License Application for Breyanzi for the treatment of relapsed or refractory LBCL after failure of first-line therapy is currently under Priority Review with the U.S. Food and Drug Administration (FDA), with an assigned Prescription Drug User Fee Act (PDUFA) goal date of June 24, 2022.

Breyanzi, a differentiated CD-19 directed CAR T cell therapy, is currently approved by the FDA for the treatment of adult patients with relapsed or refractory LBCL after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B. Breyanzi is not indicated for the treatment of patients with primary central nervous system lymphoma.

About Breyanzi

Breyanzi is a CD-19 directed chimeric antigen receptor (CAR) T cell therapy, administered as a defined composition to reduce variability of the CD8 and CD4 component dose. Breyanzi has a 4-1BB costimulatory domain which enhances the expansion and persistence of the CAR T cells. Breyanzi was previously approved by the U.S. Food and Drug Administration for the treatment of adult patients with relapsed or refractory LBCL after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B. Breyanzi is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS.

Breyanzi is also approved in the European Union, Switzerland, Japan and Canada for relapsed and refractory LBCL after two or more lines of systemic therapy. Bristol Myers Squibb’s clinical development program for Breyanzi includes clinical studies in earlier lines of treatment for patients with relapsed or refractory LBCL and other types of lymphomas and leukemia. For more information, visit clinicaltrials.gov.

Breyanzi is not approved in any region for the second-line treatment of LBCL.

About PILOT

PILOT (NCT03483103) is a multicenter Phase 2 trial evaluating Breyanzi as a second-line therapy in adults with relapsed or refractory large B-cell lymphoma after first-line therapy who are ineligible for hematopoietic stem cell transplant (HSCT). All enrolled patients have relapsed or refractory large B-cell lymphoma after treatment with a single line of chemoimmunotherapy containing an anthracycline and a CD20-targeted agent and have been deemed non-candidates for high-dose chemotherapy and HSCT. The primary endpoint of the study is overall response rate. Other efficacy endpoints include complete response rate, duration of response, progression-free survival, event-free survival and overall survival.

Important Safety Information

BOXED WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITIES

Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving BREYANZI. Do not administer BREYANZI to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab with or without corticosteroids.
Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving BREYANZI, including concurrently with CRS, after CRS resolution or in the absence of CRS. Monitor for neurologic events after treatment with BREYANZI. Provide supportive care and/or corticosteroids as needed.
BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS.
Cytokine Release Syndrome (CRS)

CRS, including fatal or life-threatening reactions, occurred following treatment with BREYANZI. CRS occurred in 46% (122/268) of patients receiving BREYANZI, including ≥ Grade 3 (Lee grading system) CRS in 4% (11/268) of patients. One patient had fatal CRS and 2 had ongoing CRS at time of death. The median time to onset was 5 days (range: 1 to 15 days). CRS resolved in 119 of 122 patients (98%) with a median duration of 5 days (range: 1 to 17 days). Median duration of CRS was 5 days (range 1 to 30 days) in all patients, including those who died or had CRS ongoing at time of death.

Among patients with CRS, the most common manifestations of CRS include fever (93%), hypotension (49%), tachycardia (39%), chills (28%), and hypoxia (21%). Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, diffuse alveolar damage, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).

Ensure that 2 doses of tocilizumab are available prior to infusion of BREYANZI. Sixty-one of 268 (23%) patients received tocilizumab and/or a corticosteroid for CRS after infusion of BREYANZI. Twenty-seven (10%) patients received tocilizumab only, 25 (9%) received tocilizumab and a corticosteroid, and 9 (3%) received corticosteroids only.

Neurologic Toxicities

Neurologic toxicities that were fatal or life-threatening, occurred following treatment with BREYANZI. CAR T cell-associated neurologic toxicities occurred in 35% (95/268) of patients receiving BREYANZI, including ≥ Grade 3 in 12% (31/268) of patients. Three patients had fatal neurologic toxicity and 7 had ongoing neurologic toxicity at time of death. The median time to onset of the first event was 8 days (range: 1 to 46 days). The onset of all neurologic events occurred within the first 8 weeks following BREYANZI infusion. Neurologic toxicities resolved in 81 of 95 patients (85%) with a median duration of 12 days (range: 1 to 87 days). Three of four patients with ongoing neurologic toxicity at data cutoff had tremor and one subject had encephalopathy. Median duration of neurologic toxicity was 15 days (range: 1 to 785 days) in all patients, including those with ongoing neurologic events at the time of death or at data cutoff.

Seventy-eight (78) of 95 (82%) patients with neurologic toxicity experienced CRS. Neurologic toxicity overlapped with CRS in 57 patients. The onset of neurologic toxicity was after onset of CRS in 30 patients, before CRS onset in 13 patients, same day as CRS onset in 7 patients, and same day as CRS resolution in 7 patients.

Neurologic toxicity resolved in three patients before the onset of CRS. Eighteen patients experienced neurologic toxicity after resolution of CRS.

The most common neurologic toxicities included encephalopathy (24%), tremor (14%), aphasia (9%), delirium (7%), headache (7%), dizziness (6%), and ataxia (6%). Serious events including cerebral edema and seizures occurred with BREYANZI. Fatal and serious cases of leukoencephalopathy, some attributable to fludarabine, have occurred in patients treated with BREYANZI.

CRS and Neurologic Toxicities Monitoring

Monitor patients daily at a certified healthcare facility during the first week following infusion, for signs and symptoms of CRS and neurologic toxicities. Monitor patients for signs and symptoms of CRS and neurologic toxicities for at least 4 weeks after infusion; evaluate and treat promptly. Counsel patients to seek immediate medical attention should signs or symptoms of CRS or neurologic toxicity occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab or tocilizumab and corticosteroids as indicated.

BREYANZI REMS

Because of the risk of CRS and neurologic toxicities, BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS. The required components of the BREYANZI REMS are:

Healthcare facilities that dispense and administer BREYANZI must be enrolled and comply with the REMS requirements.
Certified healthcare facilities must have on-site, immediate access to tocilizumab.
Ensure that a minimum of 2 doses of tocilizumab are available for each patient for infusion within 2 hours after BREYANZI infusion, if needed for treatment of CRS.
Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer BREYANZI are trained on the management of CRS and neurologic toxicities.
Further information is available at www.BreyanziREMS.com, or contact Bristol Myers Squibb at 1-888-423-5436.

Hypersensitivity Reactions

Allergic reactions may occur with the infusion of BREYANZI. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO).

Serious Infections

Severe infections, including life-threatening or fatal infections, have occurred in patients after BREYANZI infusion. Infections (all grades) occurred in 45% (121/268) of patients. Grade 3 or higher infections occurred in 19% of patients. Grade 3 or higher infections with an unspecified pathogen occurred in 16% of patients, bacterial infections occurred in 5%, and viral and fungal infections occurred in 1.5% and 0.4% of patients, respectively. Monitor patients for signs and symptoms of infection before and after BREYANZI administration and treat appropriately. Administer prophylactic antimicrobials according to standard institutional guidelines.

Febrile neutropenia has been observed in 9% (24/268) of patients after BREYANZI infusion and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids, and other supportive care as medically indicated.

Avoid administration of BREYANZI in patients with clinically significant active systemic infections.

Viral reactivation: Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against B cells. Ten of the 11 patients in the TRANSCEND study with a prior history of HBV were treated with concurrent antiviral suppressive therapy to prevent HBV reactivation during and after treatment with BREYANZI. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing.

Prolonged Cytopenias

Patients may exhibit cytopenias not resolved for several weeks following lymphodepleting chemotherapy and BREYANZI infusion. Grade 3 or higher cytopenias persisted at Day 29 following BREYANZI infusion in 31% (84/268) of patients, and included thrombocytopenia (26%), neutropenia (14%), and anemia (3%). Monitor complete blood counts prior to and after BREYANZI administration.

Hypogammaglobulinemia

B-cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with BREYANZI. The adverse event of hypogammaglobulinemia was reported as an adverse reaction in 14% (37/268) of patients; laboratory IgG levels fell below 500 mg/dL after infusion in 21% (56/268) of patients. Hypogammaglobulinemia, either as an adverse reaction or laboratory IgG level below 500 mg/dL after infusion, was reported in 32% (85/268) of patients. Monitor immunoglobulin levels after treatment with BREYANZI and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement as clinically indicated.

Live vaccines: The safety of immunization with live viral vaccines during or following BREYANZI treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during BREYANZI treatment, and until immune recovery following treatment with BREYANZI.

Secondary Malignancies

Patients treated with BREYANZI may develop secondary malignancies. Monitor lifelong for secondary malignancies. In the event that a secondary malignancy occurs, contact Bristol Myers Squibb at 1-888-805-4555 for reporting and to obtain instructions on collection of patient samples for testing.

Effects on Ability to Drive and Use Machines

Due to the potential for neurologic events, including altered mental status or seizures, patients receiving BREYANZI are at risk for altered or decreased consciousness or impaired coordination in the 8 weeks following BREYANZI administration. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.

Adverse Reactions

Serious adverse reactions occurred in 46% of patients. The most common nonlaboratory, serious adverse reactions (> 2%) were CRS, encephalopathy, sepsis, febrile neutropenia, aphasia, pneumonia, fever, hypotension, dizziness, and delirium. Fatal adverse reactions occurred in 4% of patients.

The most common nonlaboratory adverse reactions of any grade (≥ 20%) were fatigue, CRS, musculoskeletal pain, nausea, headache, encephalopathy, infections (pathogen unspecified), decreased appetite, diarrhea, hypotension, tachycardia, dizziness, cough, constipation, abdominal pain, vomiting, and edema.

Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide.

Bristol Myers Squibb: Creating a Better Future for People with Cancer

Bristol Myers Squibb is inspired by a single vision—transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus. Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.

Learn more about the science behind cell therapy and ongoing research at Bristol Myers Squibb here.

On May 26, 2022 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel T cell-based cancer immunotherapies (tumor infiltrating lymphocyte, TIL, and peripheral-blood lymphocyte, PBL), reported clinical results from its C-144-01 clinical study in patients with advanced (unresectable or metastatic) melanoma who progressed on prior anti-PD-1/L1 therapy, and if BRAF mutation positive, also on prior BRAF or BRAF/MEK inhibitor therapy (Press release, Iovance Biotherapeutics, MAY 26, 2022, View Source [SID1234615089]).

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In registrational Cohort 4 (n=87), the objective response rate (ORR) by an independent review committee (IRC) using RECIST 1.1 criteria was 29% (95% confidence interval (CI): 19.5%, 39.4%) with three complete responses and 22 partial responses. The median duration of response (DOR) in Cohort 4 by IRC was 10.4 months with a median study follow-up of 23.5 months. These data demonstrate that one-time treatment with lifileucel therapy may provide meaningful benefit in heavily pre-treated patients. Cohort 4’s findings are supported by Cohort 2 (n=66), where the ORR by IRC was 35% (95% CI: 23.5%, 47.6%) with five complete responses and 18 partial responses. The median DOR in Cohort 2 was not reached with a median study follow-up of 36.6 months. The ORR by IRC for pooled patients (n=153) from both Cohorts 2 and 4 was 31% (95% CI: 24.1%, 39.4%) and median DOR was not reached at a median study follow up of 27.6 months.

Patients in Cohort 4 exhibited higher baseline disease burden in comparison to patients in Cohort 2, including a substantially higher proportion of patients with elevated baseline lactate dehydrogenase (LDH) levels, a well-known negative prognostic factor (64.4% versus 40.9%), as well as a greater number of tumor lesions at baseline (83.9% versus 65.2% with more than three lesions). In addition, patients in Cohort 2 also had approximately half the cumulative duration of anti-PD-1 therapy before lifileucel therapy in comparison to patients in Cohort 4. Reduced duration of prior anti-PD-1 therapy was shown1 to be associated with an increase of DOR to lifileucel. The treatment-emergent adverse event profile in both cohorts was consistent with the underlying disease and known adverse event profiles of non-myeloablative lymphodepletion and interleukin-2 (IL-2) and was also consistent between Cohorts 2 and 4.

Iovance plans to present additional data from Cohorts 2 and 4 at a medical meeting in the second half of 2022. The planned BLA submission for lifileucel in advanced melanoma using these data remains on track for August 2022.

Frederick Vogt, Ph.D., J.D., Interim President and Chief Executive Officer of Iovance, stated, "We are pleased to report positive results for lifileucel from the registrational Cohort 4 data from the C-144-01 study. Iovance is proceeding towards submission of a BLA in August 2022 using these results as well as the potentially supportive results from Cohort 2 of the C-144-01 study. We thank our patients, their families, and our investigators, employees, shareholders, and advocates for their support. We look forward to reporting further progress with our lifileucel BLA and launch preparations in 2022."

Friedrich Graf Finckenstein, M.D., Chief Medical Officer of Iovance, commented, "Treatment of melanoma patients after failure of anti-PD-1 therapy remains a critical unmet medical need without an approved therapeutic option. Available care for metastatic melanoma patients in this setting is chemotherapy, which has been reported to offer a four to ten percent response rate with a very short median duration of response. We are excited about the results from registrational Cohort 4 of the C-144-01 study and the potential of lifileucel as a new treatment option for these patients."

Webcast and Conference Call

Iovance will host a conference call today at 5:00 p.m. ET to discuss the updates for the C-144-01 clinical study. The conference call dial-in numbers are 1 (844) 646-4465 (domestic) or 1 (615) 247-0257 (international) and the conference ID is #5945054. The live webcast can be accessed in the Investors section of the company’s website at View Source The archived webcast will be available for a year in the Investors section at www.iovance.com.

1Larkin, J.M.G., et al., Lifileucel (LN-144), a Cryopreserved Autologous Tumor Infiltrating Lymphocyte (TIL) Therapy in Patients with Advanced Melanoma: Evaluation of Impact of Prior Anti–PD-1 Therapy, ASCO (Free ASCO Whitepaper) Annual Meeting, June 6, 2021. Presentation.

On May 26, 2022 Veracyte, Inc. (Nasdaq: VCYT) reported that new data from a clinical research study demonstrating the ability of its Immunoscore Immune Checkpoint (IC) assay to predict which patients with metastatic non-small cell lung cancer (NSCLC) may benefit from immune checkpoint inhibitors (ICIs) (Press release, Veracyte, MAY 26, 2022, View Source [SID1234615105]). The findings will be shared in an oral presentation at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago on June 6 at 1:15 p.m. CDT.

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"Immune checkpoint inhibitors have revolutionized therapeutic management of patients with metastatic non-small cell lung cancer," said Jérôme Galon, Ph.D., of Inserm, the National Institute of Health and Medical Research in France, and Veracyte. "Unfortunately, current biomarkers are limited for identifying responders as only a handful of these patients benefit from ICIs. Our findings are exciting because they underscore the Immunoscore IC assay as a tool for predicting which patients may benefit from ICIs, potentially avoiding the use of costly drugs and unnecessary additional toxicity for non-responder patients."

For the study, researchers evaluated the Immunoscore IC assay in two independent cohorts totaling 265 patients who were treated with anti-PD1 or anti-PD-L1 antibodies (immune checkpoint inhibitors). The Immunoscore IC assay provided a risk score that was significantly associated with patients’ progression-free survival and overall survival. Within the two cohorts, all patients (100 percent) with a "high-risk" Immunoscore IC result relapsed in less than 18 months. In contrast, 34 percent and 33 percent of patients with a "low-risk" Immunoscore IC result did not relapse for a period of at least 36 months, in each cohort.

"These findings suggest that the Immunoscore IC assay may help biopharmaceutical companies select the right patients, helping to improve the success rate of their clinical trials, notably in combination trials including ICIs," said Corinne Danan, general manager for Veracyte’s Biopharma business unit. "Further, we believe the test’s use could help enable patients who are unlikely to respond to ICIs to enter into novel, combination-immunotherapy trials."

About Immunoscore IC

Immunoscore IC is a novel assay designed to help predict a patient’s response to immune checkpoint inhibitors. The assay measures the densities of PD-L1+ and CD8+ cells, as well as the proximity among these cells on a single tissue section using imaging tools, and then produces a risk score based on a proprietary algorithm. The Immunoscore IC assay is available as a service for biopharmaceutical companies and is part of the Immunoscore family of assays. These assays measure the immune reaction in and around the tumor and help to determine drugs’ mechanisms of action and their impact on the tumor microenvironment (TME). The Immunoscore Colon Cancer test is available clinically and analyzes T lymphocyte infiltration at the tumor site to help guide treatment decisions in localized colon cancer.

On May 26, 2022 Merck, a leading science and technology company, reported the latest research representing the Company’s innovative oncology portfolio has been accepted for presentation at this year’s American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, June 3-7, 2022 (Press release, Merck & Co, MAY 26, 2022, View Source [SID1234615121]). Data encompass Company-sponsored, investigator-sponsored, and external collaboration studies.

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Abstracts to be shared at the meeting include data for the Company’s licensed medicines BAVENCIO (avelumab), TEPMETKO (tepotinib) and ERBITUX (cetuximab), and its oncology pipeline. The presentations span key tumor types including advanced urothelial carcinoma (UC), advanced renal cell carcinoma (RCC), metastatic non-small cell lung cancer (NSCLC), metastatic colorectal cancer (CRC), and head and neck cancer (SCCHN).

"We look forward to coming together with the scientific community at ASCO (Free ASCO Whitepaper) 2022, where we will share the latest data from our portfolio, which demonstrate our determination to make a real difference in the lives of patients with some of the most challenging cancers," said Victoria Zazulina, Head of Development Unit, Oncology, for the Healthcare business of Merck.

Select presentations include:

BAVENCIO (avelumab): New analyses of long-term data from the Phase III JAVELIN Bladder 100 study of BAVENCIO as first-line maintenance treatment in advanced UC, including data from subgroups defined by best response to first-line chemotherapy and in patients who did or did not receive second-line treatment after BAVENCIO maintenance.
TEPMETKO (tepotinib): Data for the oral MET inhibitor TEPMETKO include two poster presentations from the VISION trial reporting efficacy, safety and quality-of-life results of TEPMETKO in Asian patients with METex14 skipping NSCLC, and updated efficacy and safety results of TEPMETKO and exploratory biomarker analyses in patients with NSCLC with high-level MET amplification enrolled into Cohort B of the VISION trial based on liquid biopsy.
ERBITUX (cetuximab): Abstracts from key investigator-sponsored studies (ISS) exploring ERBITUX-based combinations, including the Phase III FIRE-4 study of early switch-maintenance from ERBITUX/FOLFIRI to bevacizumab/5-FU and rechallenge in later lines for RAS wild-type mCRC patients, and the Phase II AVETUXIRI study evaluating BAVENCIO combined with ERBITUX and irinotecan for refractory microsatellite stable metastatic colorectal cancer.
Berzosertib: Results from research collaborations assessing the intravenous ataxia telangiectasia-mutated and Rad3-related protein kinase (ATR) inhibitor berzosertib, including the National Cancer Institute’s (NCI) Cancer Therapy Evaluation Program 9938 Phase I study of berzosertib plus irinotecan in patients with advanced solid tumors and NCI single-arm Phase II data of berzosertib plus topotecan in patients with relapsed extra-pulmonary small cell neuroendocrine carcinomas.
Below is a selection of key Merck-related abstracts accepted for presentation at ASCO (Free ASCO Whitepaper) 2022:

Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (aUC): long-term outcomes from JAVELIN Bladder 100 in subgroups defined by response to 1L chemotherapy

Randomized study to investigate a switch maintenance concept with 5-FU plus Bevacizumab after FOLFIRI plus Cetuximab induction treatment versus continued treatment with FOLFIRI plus cetuximab: report of a secondary endpoint of the phase-III FIRE-4 study (AIO KRK-0114)

*These studies are sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, under its Cooperative Research and Development Agreement with Merck for M6620.

All Merck press releases are distributed by e-mail at the same time they become available on the Merck website. Please go to www.merckgroup.com/subscribe to register online, change your selection or discontinue this service.

Commitment to Cancer
Merck is a science-led organization dedicated to delivering transformative medicines with the goal of making a meaningful difference in the lives of people affected by cancer. Our oncology research efforts aim to leverage our synergistic portfolio in oncogenic pathways, immuno-oncology, and DNA Damage Response (DDR) to tackle challenging tumor types in gastrointestinal, genitourinary, and thoracic cancers. Our curiosity drives our pursuit of treatments for even the most complex cancers, as we work to illuminate a path to scientific breakthroughs that transform patient outcomes. Learn more at www.merckgrouponcology.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.7-9 In November 2014, Merck and Pfizer announced a strategic alliance to co-develop and co-commercialize BAVENCIO.

BAVENCIO Approved Indications
The European Commission (EC) has authorized the use of BAVENCIO as monotherapy for the first-line maintenance treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC) who are progression-free following platinum-based chemotherapy. BAVENCIO in combination with axitinib is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC). BAVENCIO is also authorized by the EC for use as a monotherapy for the treatment of adult patients with metastatic Merkel cell carcinoma (MCC).

In the US, BAVENCIO is indicated 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 axitinib is indicated in the US for the first-line treatment of patients with advanced RCC. Additionally, the US Food and Drug Administration (FDA) granted accelerated approval for BAVENCIO for the treatment of adults and pediatric patients 12 years and older with metastatic MCC. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication 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 Safety Profile from the EU Summary of Product Characteristics (SmPC)
The special warnings and precautions for use for BAVENCIO monotherapy include infusion-related reactions, as well as immune-related adverse reactions that include pneumonitis and hepatitis (including fatal cases), colitis, pancreatitis (including fatal cases), myocarditis (including fatal cases), endocrinopathies, nephritis and renal dysfunction, and other immune-related adverse reactions. The special warnings and precautions for use for BAVENCIO in combination with axitinib include hepatotoxicity.

The SmPC list of the most common adverse reactions with BAVENCIO monotherapy in patients with solid tumors includes fatigue, nausea, diarrhea, decreased appetite, constipation, infusion-related reactions, weight decreased and vomiting. The list of most common adverse reactions with BAVENCIO in combination with axitinib includes diarrhea, hypertension, fatigue, nausea, dysphonia, decreased appetite, hypothyroidism, cough, headache, dyspnea, and arthralgia.

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, 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 U.S. 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 U.S. with metastatic NSCLC with METex14 skipping alterations. Tepotinib is available in a number of countries, and under review by various other regulatory authorities globally. To meet an urgent clinical need, tepotinib 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 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 Safety Profile from the EU Summary of Product Characteristics (SmPC)
The special warnings and precautions for use for TEPMETKO monotherapy include Interstitial lung disease (ILD) or ILD-like adverse reactions including pneumonitis, increase of Liver enzymes (ALT and AST), QTc prolongation, and embryo-foetal toxicity.

The most common adverse reactions in ≥ 20% of exposed to tepotinib at the recommended dose in the target indication are oedema, mainly peripheral oedema, nausea, hypoalbuminaemia, diarrhoea and increase in creatinine. The most common serious adverse reactions in ≥ 1% of patients are peripheral oedema, generalised oedema and ILD.

About Berzosertib (M6620)
Berzosertib is an investigational, intravenous, potent and selective inhibitor of the ataxia telangiectasia and Rad3-related (ATR) protein that blocks ATR activity in cells. Berzosertib is the first ATR inhibitor evaluated in a randomized clinical trial in any tumor type, and it is the lead candidate in Merck’s DNA Damage Response (DDR) inhibitor portfolio. It is currently being investigated in a number of internal and external studies with early phase I/II data in small cell lung cancer, ovarian cancer, and various solid tumors. Berzosertib, formerly known as VX-970, was licensed from Vertex Pharmaceuticals in 2017. Berzosertib is not approved for any use anywhere in the world.

About ERBITUX (cetuximab)
ERBITUX is an IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR). As a monoclonal antibody, the mode of action of ERBITUX is distinct from standard non-selective chemotherapy treatments in that it specifically targets and binds to the EGFR. This binding inhibits the activation of the receptor and the subsequent signal-transduction pathway, which results in reducing both the invasion of normal tissues by tumor cells and the spread of tumors to new sites. It is also believed to inhibit the ability of tumor cells to repair the damage caused by chemotherapy and radiotherapy and to inhibit the formation of new blood vessels inside tumors, which appears to lead to an overall suppression of tumor growth. Based on in vitro evidence, ERBITUX also targets cytotoxic immune effector cells towards EGFR-expressing tumor cells (antibody-dependent cell-mediated cytotoxicity [ADCC]).

ERBITUX has already obtained market authorization in over 100 countries worldwide for the treatment of RAS wild-type metastatic colorectal cancer and for the treatment of squamous cell carcinoma of the head and neck. Merck licensed the right to market ERBITUX, a registered trademark of ImClone LLC, outside the U.S. and Canada from ImClone LLC, a wholly owned subsidiary of Eli Lilly and Company, in 1998.