Opdivo (nivolumab) Demonstrates Statistically Significant Overall Survival Benefit Versus Chemotherapy in Patients with Advanced Esophageal Cancer

Opdivo demonstrated a 23% reduction in the risk of death and 2.5-month improvement in median overall survival compared to chemotherapy

Results from Phase 3 ATTRACTION-3 trial to be featured in a Presidential Symposium during the European Society for Medical Oncology 2019 Annual Congress

PRINCETON, NJ, USA I September 30, 2019 IBristol-Myers Squibb Company (NYSE: BMY) and Ono Pharmaceutical Co., Ltd. today announced results from the Phase 3 ATTRACTION-3 trial evaluating Opdivo (nivolumab) versus chemotherapy (docetaxel or paclitaxel) for the treatment of patients with unresectable advanced or recurrent esophageal squamous cell carcinoma (ESCC) refractory or intolerant to combination therapy with fluoropyrimidine and platinum-based drugs. For the primary endpoint of overall survival (OS), Opdivo demonstrated a statistically significant improvement over chemotherapy, with a 23% reduction in risk of death [Hazard Ratio (HR) 0.77; 95% Confidence Interval (CI): 0.62 to 0.96; p=0.019] and a 2.5-month improvement in median OS [10.9 months (95% CI: 9.2 to 13.3)] compared to patients treated with chemotherapy [8.4 months (95% CI: 7.2 to 9.9)]. The safety profile of Opdivo in this trial was consistent with previously reported studies in ESCC and other solid tumors.

These data (Presentation #LBA11) will be featured in the Presidential Symposium on Monday, September 30 from 4:30-6:15 PM CEST at the European Society for Medical Oncology (ESMO) 2019 Annual Congress in Barcelona, Spain and simultaneously published in The Lancet Oncology.

Patients treated in the Opdivo arm showed 12- and 18-month OS rates of 47% (95% CI: 40 to 54) and 31% (95% CI: 24 to 37), respectively, versus 34% (95% CI: 28 to 41) and 21% (95% CI: 15 to 27) among patients in the chemotherapy arm. Survival benefit with Opdivo was observed regardless of tumor PD-L1 expression levels. An exploratory analysis of patient-reported outcomes showed significant overall improvement in quality of life with Opdivo versus chemotherapy.

“The significant survival benefit coupled with the favorable safety profile and patient-reported outcomes observed in this trial suggest Opdivo has the potential to represent an important new second-line treatment option for patients with advanced esophageal squamous cell carcinoma, offering the possibility to extend their survival and improve their quality of life during treatment,” said Dr. Byoung Chul Cho, Professor, Yonsei Cancer Center, Yonsei University College of Medicine.

The objective response rates (ORR) between the two arms were comparable at 19% (95% CI: 14 to 26) among patients receiving Opdivo versus 22% (95% CI: 15 to 29) among those receiving chemotherapy. However, the study showed Opdivo substantially increased the median duration of response (DoR) for patients [6.9 months (95% CI: 5.4 to 11.1) versus 3.9 months (95% CI: 2.8 to 4.2)]. Seven patients in the Opdivo arm had ongoing responses at data cutoff compared to two patients in the chemotherapy arm. An overall HR of 1.08 (95% CI: 0.87 to 1.34) suggested no meaningful difference in progression-free survival (PFS) between the Opdivo and chemotherapy arms.

“These are very promising results for patients with advanced esophageal squamous cell carcinoma for whom prognosis is typically poor and are particularly important given Opdivo improved survival regardless of PD-L1 status,” said Ian M. Waxman, M.D., development lead, Gastrointestinal Cancers, Bristol-Myers Squibb. “We are encouraged to see important progress being made in this tumor type and look forward to broadening our research in gastrointestinal tumors.”

Fewer treatment-related adverse events (TRAEs) were reported with Opdivo versus chemotherapy, with a rate of 66% of any grade TRAEs for patients receiving Opdivo compared to 95% for patients receiving chemotherapy. Patients in the Opdivo arm also experienced a lower incidence of Grade 3 or 4 TRAEs compared to those in the chemotherapy arm (18% versus 63%), and the percentage of patients experiencing TRAEs leading to discontinuation was the same in both arms (9%).

About ATTRACTION-3

ATTRACTION-3 (ONO-4538-24/CA209-473; NCT02569242) is a Phase 3, multi-center, randomized, open-label global study, evaluating Opdivo versus chemotherapy (docetaxel or paclitaxel) for patients with esophageal cancer refractory or intolerant to first-line combination therapy with fluoropyrimidine and platinum-based drugs. Patient enrollment occurred predominantly in Asia with 96% of patients in both treatment arms from Asia. Patients were treated until disease progression or unacceptable toxicity. The primary endpoint of the trial is OS. Secondary endpoints include investigator-assessed ORR, PFS, disease control rate, DoR and safety. This trial was sponsored by Ono Pharmaceutical Co. Ltd. of Japan, Bristol-Myers Squibb’s development partner for Opdivo.

About Esophageal Cancer

Esophageal cancer is the seventh most common cancer and the sixth most common cause of death from cancer worldwide. The five-year relative survival rate is 8% or less for patients diagnosed with metastatic disease. The two most common types of esophageal cancer are squamous cell carcinoma and adenocarcinoma, which account for approximately 90% and 10% of all esophageal cancers, respectively. Each year, an estimated 572,000 new cases are diagnosed and approximately half a million deaths are caused by esophageal cancer. The majority of cases are diagnosed in the advanced setting and impact a patient’s daily life, including their ability to eat and drink. The prevalence of esophageal cancer is highest in Asia, with over 444,000 cases diagnosed yearly, accounting for about 80% of all esophageal cancer cases worldwide.

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.

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.

SOURCE: Bristol-Myers Squibb

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