Opdivo (nivolumab) Plus Chemotherapy Demonstrated Significant Overall and Progression-Free Survival Benefits Versus Chemotherapy in First-Line Treatment of Gastric and Esophageal Cancers

Overall survival and progression-free survival benefit observed in patients whose tumors express PD-L1; overall survival benefit also observed in all-randomized population

Efficacy benefit observed across patients with gastric cancer, gastroesophageal junction cancer or esophageal adenocarcinoma

Primary results from Phase 3 CheckMate -649 trial featured in official Press Programme and selected for presentation during a Presidential Symposium at the European Society for Medical Oncology Virtual Congress 2020

PRINCETON, NJ, USA I September 21, 2020 IBristol Myers Squibb (NYSE: BMY) today announced primary results from CheckMate -649, the pivotal Phase 3 trial in which first-line treatment with Opdivo (nivolumab) plus chemotherapy showed a statistically significant and clinically meaningful improvement in the overall survival (OS) and progression-free survival (PFS) of patients with unresectable advanced or metastatic gastric cancer, gastroesophageal junction (GEJ) cancer or esophageal adenocarcinoma compared to treatment with chemotherapy alone. Opdivo is the first PD-1 inhibitor to demonstrate superior OS and PFS in combination with chemotherapy when compared to chemotherapy alone in patients with gastric cancer, GEJ cancer or esophageal adenocarcinoma. The OS and PFS benefits were observed in patients whose tumors express PD-L1 with a combined positive score (CPS) ≥ 5, achieving both of the trial’s primary endpoints. The OS benefit was also observed in the all-randomized trial population.

Median OS (Hazard Ratio [HR]: 0.71; 98.4% Confidence Interval [CI]: 0.59 to 0.86; p<0.0001) for Opdivo plus chemotherapy was 14.4 months (95% CI: 13.1 to 16.2) compared to 11.1 months (95% CI: 10.0 to 12.1) for chemotherapy alone among PD-L1 positive patients with CPS ≥ 5. The median PFS (HR: 0.68; 98% CI: 0.56 to 0.81; p<0.0001) was 7.7 months (95% CI: 7.0 to 9.2) in those treated with Opdivo plus chemotherapy and 6.0 months (95% CI: 5.6 to 6.9) among those treated with chemotherapy alone. The safety profiles of Opdivo and chemotherapy in this trial were reflective of the known safety profiles of Opdivo and chemotherapy with no new safety signals observed.

CheckMate -649 is the largest randomized, global Phase 3 study of an immune checkpoint inhibitor-based therapy in the first-line setting for patients with gastric and esophageal cancers conducted to date.

“Currently, the first-line standard of care for patients with advanced or metastatic non-HER2 positive gastric or gastroesophageal junction cancer is chemotherapy. While it has been an important treatment option for these patients, chemotherapy alone is associated with a marginal survival benefit of often less than one year from the time a patient’s treatment is initiated,” said Markus Moehler, M.D., Professor of Gastrointestinal Oncology, Johannes-Gutenberg University Medical Center, Mainz. “Innovative treatments are urgently needed for patients around the world who are living with these advanced or metastatic upper gastrointestinal cancers, as there are currently no approved immunotherapy options in the first-line setting.”

The statistically significant OS benefit shown with Opdivo plus chemotherapy was also observed in PD-L1 positive patients with CPS ≥ 1 and in the all-randomized population. In the all-randomized population, the median OS was 13.8 months (95% CI: 12.6 to 14.6) for patients receiving Opdivo plus chemotherapy compared to 11.6 months (95% CI: 10.9 to 12.5) for patients receiving chemotherapy alone (HR: 0.80; 99.3% CI: 0.68 to 0.94; p=0.0002). In PD-L1 positive patients with CPS ≥ 1, median OS was 14.0 months (95% CI: 12.6 to 15.0) for patients receiving Opdivo plus chemotherapy compared to 11.3 months (95% CI: 10.6 to 12.3) for patients receiving chemotherapy alone (HR: 0.77; 99.3% CI: 0.64 to 0.92; p=0.0001).

“CheckMate -649 recently became the first global study in over a decade to demonstrate a significant overall survival benefit over chemotherapy in the first-line setting of non-HER2 positive gastric cancer, gastroesophageal junction cancer or esophageal adenocarcinoma, highlighting the potential of Opdivo plus chemotherapy to become a new standard of care for these patients, regardless of their tumor location,” said Ian M. Waxman, M.D., development lead, Gastrointestinal Cancers, Bristol Myers Squibb. “These available results of the CheckMate -649 study will be discussed with global health authorities as we strive to bring this important new treatment option to patients in need.”

The incidence of serious treatment-related adverse events (TRAEs), any grade and Grade 3-4, was modestly higher among patients treated with Opdivo plus chemotherapy (any grade 22%, Grade 3-4 17%) compared to patients treated with chemotherapy alone (any grade 12%, Grade 3-4 10%). Of patients treated with Opdivo plus chemotherapy, 36% and 17% experienced TRAEs of any grade or Grade 3-4 leading to discontinuation, compared to 24% and 9% of patients treated with chemotherapy. The incidence of TRAEs in patients treated with Opdivo plus chemotherapy was consistent across patient sub-groups.

These data (Presentation #LBA6_PR) will be featured in a Presidential Symposium at the European Society for Medical Oncology (ESMO) Virtual Congress 2020 on September 21 from 18:30-18:42 CEST.

About CheckMate -649

Checkmate -649 is a Phase 3 randomized, multi-center, open-label study evaluating Opdivo plus chemotherapy or the Opdivo plus Yervoy (ipilimumab) combination compared to chemotherapy alone in patients with previously untreated, non-HER2-positive, advanced or metastatic gastric cancer, GEJ cancer or esophageal adenocarcinoma. The primary endpoints of the trial are OS in PD-L1 positive patients with a combined positive score (CPS) ≥ 5 treated with Opdivo plus chemotherapy and PFS, as assessed by Blinded Independent Central Review (BICR), in CPS ≥ 5 patients treated with Opdivo plus chemotherapy compared to chemotherapy alone. Key secondary endpoints include OS in CPS ≥ 1 and all-randomized patients treated with Opdivo plus chemotherapy as well as OS and time to symptom deterioration (TTSD) in patients treated with Opdivo plus Yervoy compared to chemotherapy alone.

Patients in the Opdivo plus chemotherapy arm received Opdivo 360 mg plus capecitabine and oxaliplatin (CapeOX) every three weeks or Opdivo 240 mg plus 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX) every two weeks. Patients in the Opdivo plus Yervoy arm received Opdivo 1 mg/kg plus Yervoy 3 mg/kg every three weeks for four cycles followed by Opdivo 240 mg every two weeks. Patients in the chemotherapy arm received FOLFOX or CapeOX every two or three weeks, respectively. All patients continued treatment for two years or until disease progression, unacceptable toxicity or withdrawal of consent.

About Gastric Cancer

Gastric cancer, also known as stomach cancer, is the fifth most common cancer and the third leading cause of cancer death worldwide, with over 1,000,000 new cases and approximately 783,000 deaths in 2018. There are several cancers that can be classified as gastric cancer, including certain types of cancers that form in the GEJ, the area of the digestive tract where the esophagus and stomach connect. While GEJ cancer has a lower prevalence than gastric cancer, it continues to rise. First-line treatment for patients with gastric or GEJ cancer often provides the best chance for efficacy as many patients cannot proceed to subsequent treatments in later settings due to deterioration.

About Esophageal Cancer

Esophageal cancer is the seventh most common cancer and the sixth leading cause of death from cancer worldwide, with approximately 572,000 new cases and over 508,000 deaths in 2018. The two most common types of esophageal cancer are squamous cell carcinoma and adenocarcinoma, which account for approximately 85% and 15% of all esophageal cancers, respectively, though esophageal tumor histology can vary by region with the highest rate of esophageal adenocarcinoma occurring in North America (65%). The majority of cases are diagnosed in the advanced setting and impact a patient’s daily life, including their ability to eat and drink.

Bristol Myers Squibb: Advancing Cancer Research

At Bristol Myers Squibb, patients are at the center of everything we do. The goal of our cancer research is to increase patients’ quality of life, long-term survival and make cure a possibility. We harness our deep scientific experience, cutting-edge technologies and discovery platforms to discover, develop and deliver novel treatments for patients.

Building upon our transformative work and legacy in hematology and Immuno-Oncology that has changed survival expectations for many cancers, our researchers are advancing a deep and diverse pipeline across multiple modalities. In the field of immune cell therapy, this includes registrational CAR T cell agents for numerous diseases, and a growing early-stage pipeline that expands cell and gene therapy targets, and technologies. We are developing cancer treatments directed at key biological pathways using our protein homeostasis platform, a research capability that has been the basis of our approved therapies for multiple myeloma and several promising compounds in early- to mid-stage development. Our scientists are targeting different immune system pathways to address interactions between tumors, the microenvironment and the immune system to further expand upon the progress we have made and help more patients respond to treatment. Combining these approaches is key to delivering potential new options for the treatment of cancer and addressing the growing issue of resistance to immunotherapy. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines 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.

INDICATIONS

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), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

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 overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), 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 overall response rate and duration 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.

OPDIVO® (nivolumab) is indicated for the treatment of patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.

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 227–previously untreated metastatic non-small cell lung cancer, in combination with YERVOY; Checkmate 9LA–previously untreated recurrent or metastatic non-small cell lung cancer in combination with YERVOY and 2 cycles of platinum-doublet chemotherapy by histology; 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, as a single agent or in combination with YERVOY; Checkmate 238–adjuvant treatment of melanoma; Attraction-3—esophageal squamous cell carcinoma

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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