Bristol-Myers Squibb Withdraws European Application of Opdivo (nivolumab) Plus Yervoy (ipilimumab) for the First-Line Treatment of Advanced Non-Small Cell Lung Cancer

  • U.S. application for Opdivo and Yervoy in first-line NSCLC based on CheckMate -227 study under review with PDUFA date of May 15, 2020
  • Company committed to first-line lung cancer patients in Europe, U.S. and other markets with planned filing of results from CheckMate -9LA

PRINCETON, NJ, USA I January 31, 2020 IBristol-Myers Squibb Company (NYSE:BMY) today announced that the company has withdrawn its application in the European Union (EU) for the combination of Opdivo (nivolumab) and Yervoy (ipilimumab) for the treatment of advanced non-small cell lung cancer (NSCLC) based on data from CheckMate -227. The application was originally filed in 2018 for patients with first-line NSCLC who have tumor mutational burden ≥10 mutations/megabase, based on the final analysis of progression-free survival, a co-primary endpoint in the trial. The application was subsequently amended to include the statistically significant result of overall survival, a co-primary endpoint, from CheckMate -227 Part 1a evaluating Opdivo plus Yervoy versus chemotherapy in patients whose tumors expressed PD-L1 ≥1%.

Though the Committee for Medicinal Products for Human Use (CHMP) acknowledged the integrity of the patient level data, the CHMP determined a full assessment of the application was not possible following multiple protocol changes the company made in response to rapidly evolving science and data. The company has no plans to refile this application in the EU.

“CheckMate -227 is a robust Phase 3 study of more than 1,700 patients. Opdivo plus Yervoy demonstrated a statistically and clinically significant overall survival benefit compared to chemotherapy for patients with first-line NSCLC. The durable survival benefit seen in CheckMate -227 is an important result for patients and we are disappointed with the CHMP’s position,” said Samit Hirawat, M.D., Chief Medical Officer, Bristol-Myers Squibb.

In January 2020, the U.S. Food and Drug Administration granted a Priority Review for the combination of Opdivo and Yervoy for the treatment of first-line NSCLC based on data from Part 1 of the Phase 3 CheckMate -227 trial.

Additionally, the company plans to file applications in the U.S., Europe and other markets following the positive interim results of CheckMate -9LA for the combination of Opdivo plus Yervoy administered concomitantly with a limited course of chemotherapy for the first-line treatment of NSCLC. The results from CheckMate -227 and CheckMate -9LA build on the established benefit the combination of Opdivo plus Yervoy has previously shown in first-line melanoma and renal cell carcinoma.

“Patients with lung cancer should have access to innovative new therapies that offer the promise of long-term overall survival. We are continuing to advance our application in the U.S. for CheckMate -227 and plan to file data from CheckMate -9LA in markets globally to help address the serious unmet need in first-line lung cancer,” said Hirawat.

About CheckMate -227

CheckMate -227 is a multi-part open-label Phase 3 trial evaluating Opdivo-based regimens versus platinum-doublet chemotherapy in patients with first-line advanced NSCLC across non-squamous and squamous tumor histologies:

  • Part 1:
    • Part 1a: Opdivo plus Yervoy or Opdivo monotherapy versus chemotherapy in patients whose tumors express PD-L1
    • Part 1b: Opdivo plus Yervoy or Opdivo plus chemotherapy versus chemotherapy in patients whose tumors do not express PD-L1
  • Part 2: Opdivo plus chemotherapy versus chemotherapy, regardless of PD-L1

There are two co-primary endpoints in Part 1 for Opdivo plus Yervoy (versus chemotherapy): overall survival (OS) in patients whose tumors express PD-L1 (assessed in patients enrolled in Part 1a) and progression-free survival (PFS) in patients with TMB ≥10 mut/Mb across the PD-L1 spectrum (assessed in patients enrolled across Parts 1a and 1b). Part 1 met both its co-primary endpoints of PFS with the Opdivo plus Yervoy combination versus chemotherapy in patients whose tumors have high (≥10 mutations/megabase, mut/mb) TMB, regardless of PD-L1 expression, and OS demonstrating a superior benefit for Opdivo plus Yervoy versus chemotherapy in first-line NSCLC patients whose tumors express PD-L1 ≥1%. Part 2 did not meet its primary endpoint for OS for Opdivo plus chemotherapy versus chemotherapy alone, in patients with non-squamous NSCLC.

About Lung Cancer

Lung cancer is the leading cause of cancer deaths globally. The two main types of lung cancer are non-small cell and small cell. Non-small cell lung cancer (NSCLC) is one of the most common types of lung cancer and accounts for up to 85% of diagnoses. Survival rates vary depending on the stage and type of the cancer when diagnosed. For patients diagnosed with metastatic lung cancer, the five-year survival rate is approximately 5%.

Bristol-Myers Squibb: Advancing Oncology Research

At Bristol-Myers Squibb, patients are at the center of everything we do. The focus of our research is to increase quality, long-term survival for patients and make cure a possibility. Through a unique multidisciplinary approach powered by translational science, we harness our deep scientific experience in oncology and Immuno-Oncology (I-O) research to identify novel treatments tailored to individual patient needs. Our researchers are developing a diverse, purposefully built pipeline designed to target different immune system pathways and address the complex and specific interactions between the tumor, its microenvironment and the immune system. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines, like I-O, a reality for patients.

About Opdivo

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo’s leading global development program is based on Bristol-Myers Squibb’s scientific expertise in the field of Immuno-Oncology, and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has treated more than 35,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In October 2015, the Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.

U.S. FDA-APPROVED INDICATIONS FOR OPDIVO®

OPDIVO® (nivolumab) as a single agent is indicated for the treatment of patients with unresectable or metastatic melanoma.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma.

OPDIVO® (nivolumab) is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.

OPDIVO® (nivolumab) is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with progression after platinum-based chemotherapy and at least one other line of therapy. 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.

OPDIVO® (nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of patients with intermediate or poor risk, previously untreated advanced renal cell carcinoma (RCC).

OPDIVO® (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO® (nivolumab) is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.

OPDIVO® (nivolumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma 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. 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.

OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. 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.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. 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.

OPDIVO® (nivolumab) is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO® (nivolumab) is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.

About Yervoy

Yervoy is a recombinant, human monoclonal antibody that binds to the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activity. Yervoy binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation, including the activation and proliferation of tumor infiltrating T-effector cells. Inhibition of CTLA-4 signaling can also reduce T-regulatory cell function, which may contribute to a general increase in T-cell responsiveness, including the anti-tumor immune response. On March 25, 2011, the U.S. Food and Drug Administration (FDA) approved Yervoy 3 mg/kg monotherapy for patients with unresectable or metastatic melanoma. Yervoy is approved for unresectable or metastatic melanoma in more than 50 countries. There is a broad, ongoing development program in place for Yervoy spanning multiple tumor types.

Indications and Important Safety Information for YERVOY®(ipilimumab)

Indications

YERVOY® (ipilimumab) is indicated for the treatment of unresectable or metastatic melanoma in adults and pediatric patients (12 years and older).

YERVOY® (ipilimumab) is indicated for the adjuvant treatment of patients with cutaneous melanoma with pathologic involvement of regional lymph nodes of more than 1 mm who have undergone complete resection, including total lymphadenectomy.

Checkmate Trials and Patient Populations

Checkmate 037–previously treated metastatic melanoma; Checkmate 066–previously untreated metastatic melanoma; Checkmate 067–previously untreated metastatic melanoma, as a single agent or in combination with YERVOY; Checkmate 017–second-line treatment of metastatic squamous non-small cell lung cancer; Checkmate 057–second-line treatment of metastatic non-squamous non-small cell lung cancer; Checkmate 032–small cell lung cancer; Checkmate 025–previously treated renal cell carcinoma; Checkmate 214–previously untreated renal cell carcinoma, in combination with YERVOY; Checkmate 205/039–classical Hodgkin lymphoma; Checkmate 141–recurrent or metastatic squamous cell carcinoma of the head and neck; Checkmate 275–urothelial carcinoma; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Checkmate 040–hepatocellular carcinoma; Checkmate 238–adjuvant treatment of melanoma.

About the Bristol-Myers Squibb and Ono Pharmaceutical Collaboration

In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol-Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol-Myers Squibb further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.

Celgene and Juno Therapeutics are wholly owned subsidiaries of Bristol-Myers Squibb Company. In certain countries outside the U.S., due to local laws, Celgene and Juno Therapeutics are referred to as, Celgene, a Bristol-Myers Squibb company and Juno Therapeutics, a Bristol-Myers Squibb company.

SOURCE: Bristol-Myers Squibb

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