Opdivo (Nivolumab) Plus Chemotherapy Demonstrates Significant Improvement in Overall and Progression-Free Survival as First-Line Treatment for Gastric and Esophageal Cancers

Princeton, New Jersey, USA, September 22, 2020 /PRNewswire/ -- Bristol-Myers Squibb (NYSE: BMY) today announced the primary results from the pivotal Phase III CheckMate -649 study. Compared with chemotherapy alone,Opdivo(Nivolumab) in combination with chemotherapy as first-line treatment for patients with unresectable advanced or metastatic gastric cancer, gastroesophageal junction (GEJ) cancer, or esophageal adenocarcinoma demonstrated statistically significant and clinically meaningful benefits in overall survival (OS) and progression-free survival (PFS).OpdivoIt is the first PD-1 inhibitor that, when combined with chemotherapy versus chemotherapy alone for the treatment of gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma, provides significant benefits in overall survival (OS) and progression-free survival (PFS). Benefits in OS and PFS were observed in patients with PD-L1 positivity, defined as a Combined Positive Score (CPS) ≥ 5, meeting both primary endpoints of the study. Additionally, an OS benefit was also observed in the overall randomized population.

In patients with PD-L1 positivity, defined as a Combined Positive Score (CPS) ≥ 5,OpdivoThe median OS in the combination chemotherapy group (hazard ratio [HR]: 0.71; 98.4% confidence interval [CI]: 0.59-0.86; p<0.0001) was 14.4 months (95% CI: 13.1-16.2), compared with 11.1 months (95% CI: 10.0-12.1) in the chemotherapy-alone control group.OpdivoThe median PFS was 7.7 months (95% CI: 7.0-9.2) in the combination chemotherapy group (HR: 0.68; 98% CI: 0.56-0.81; p<0.0001) versus 6.0 months (95% CI: 5.6-6.9) in the chemotherapy-alone group. In this study,OpdivoThe safety profile of the combination chemotherapy is consistent with the knownOpdivoConsistent with the safety profile of chemotherapy, no new safety signals were observed.

In studies of first-line treatment for gastric and esophageal cancers based on immune checkpoint inhibitors, CheckMate -649 isThe Largest to Dateof a randomized, global Phase III study.

“Currently, chemotherapy is the first-line standard of care for patients with advanced or metastatic HER2-negative gastric or gastroesophageal junction cancer. Although chemotherapy represents an important treatment option for these patients, those receiving chemotherapy alone as initial therapy typically achieve only limited survival benefits of less than one year,” stated Dr. Markus Moehler, Professor of Clinical Gastrointestinal Oncology at the University Medical Center of Johannes Gutenberg University Mainz. “Given that no immunotherapy regimens have yet been approved for first-line treatment in this setting, there remains an urgent unmet need for innovative therapeutic options among patients with advanced or metastatic upper gastrointestinal cancers worldwide.”

The study results showed that in PD-L1-positive patients with CPS ≥ 1 and in the overall randomized population,OpdivoCombination chemotherapy also demonstrated a statistically significant benefit in overall survival (OS). In the entire randomized population,OpdivoThe median OS for patients in the combination chemotherapy group was 13.8 months (95% CI: 12.6–14.6), patients in the chemotherapy-alone group had a median of 11.6 months (95% CI: 10.9-12.5）（HR: 0.80;  99.3% CI: 0.68–0.94; p=0.0002). In patients with PD-L1 positivity and CPS ≥1,OpdivoThe median OS for patients in the combination chemotherapy group was 14.0 months (95% CI: 12.6–15.0), and 11.3 months (95% CI: 10.6-12.3）（HR: 0.77; 99.3% CI: 0.64-0.92; p=0.0001）。

“CheckMate -649 has recently become the first global study in over a decade to demonstrate a significant overall survival benefit surpassing chemotherapy in the first-line treatment of HER2-negative gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma. Therefore, regardless of the specific location of the patient’s tumor,”Opdivo“Combination chemotherapy regimens are poised to become the new standard of first-line treatment for this patient population.” stated Dr. Ian M. Waxman, Head of Gastrointestinal Oncology R&D at Bristol-Myers Squibb: “We will engage with health authorities worldwide to discuss the existing data from the CheckMate -649 study, committed to bringing this important novel therapeutic regimen to patients who truly need it.”

In terms of all-grade and Grade 3–4 severe treatment-related adverse events (TRAEs),OpdivoThe incidence rate in patients receiving combination chemotherapy (all grades 22%, grades 3–4 17%) was slightly higher than that in patients receiving chemotherapy alone (all grades 12%, grades 3–4 10%). InOpdivoIn the combination chemotherapy group, 36% and 17% of patients discontinued treatment due to all-grade and grade 3–4 TRAEs, respectively, compared with 24% and 9% in the chemotherapy-alone group. Regarding subgroup data,OpdivoThe incidence of TRAEs in the combination chemotherapy group was generally consistent across all patient subgroups.

About CheckMate -649

CheckMate-649 is a phase III, randomized, multicenter, open-label clinical study designed to evaluate, compared with chemotherapy alone,NivolumabCombined chemotherapy orNivolumabCombinationIpilimumabEfficacy in the treatment of patients with previously untreated HER2-negative advanced or metastatic gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma. The primary endpoint of the study was compared to chemotherapy alone,NivolumabOverall survival (OS) in patients with PD-L1–positive expression, defined as a combined positive score (CPS) ≥5, treated with combination chemotherapy, as well as progression-free survival (PFS) assessed by the Blinded Independent Central Review (BICR). Key secondary endpoints included receivingNivolumabOS in patients with CPS ≥1 treated with combination chemotherapy and in all randomized patients, as well as those receivingNivolumabCombinedIpilimumabComparison of Overall Survival (OS) and Time to Symptom Deterioration (TTSD) in Patients Treated with Chemotherapy Alone.

NivolumabPatients in the combination chemotherapy group receivedNivolumab360 mg in combination with capecitabine and oxaliplatin (CapeOX) treatment, once every 3 weeks; or receiveNivolumab240 mg in combination with 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) every two weeks.NivolumabJointIpilimumabPatients in the group receivedNivolumab1 mg/kg in combinationIpilimumab3 mg/kg administered once every 3 weeks for four consecutive cycles, followed by sequentialNivolumab240 mg every 2 weeks. Patients in the chemotherapy group received either FOLFOX treatment every 2 weeks or CapeOX treatment every 3 weeks. All patients continued treatment for up to two years, or until disease progression, unacceptable toxicity, or withdrawal of informed consent.

About Gastric Cancer

Gastric cancer is the fifth most common cancer globally and the third leading cause of cancer-related deaths. In 2018, there were over 1,000,000 new cases of gastric cancer worldwide,Approximately 783,000 deathsIn China, gastric cancer is the second most common malignancy after lung cancer, accounting for 44% and 50% of the global incidence and mortality of gastric cancer, respectively. The definition of gastric cancer is relatively broad, encompassing various cancers including gastroesophageal junction (GEJ) cancer, which arises at the junction of the stomach and esophagus. Although the prevalence of GEJ cancer is lower than that of gastric cancer, it shows a continuous upward trend. Since many patients with gastric cancer become unable to tolerate subsequent treatments due to disease progression, first-line therapy often represents the best opportunity for achieving therapeutic efficacy in patients with gastric or GEJ cancer.

About Esophageal Cancer

Esophageal cancer is the seventh most common cancer and the sixth leading cause of cancer-related deaths worldwide. In 2018, there were approximately 572,000 new cases of esophageal cancer globally,Over 508,000 deaths. Although the histological characteristics of esophageal cancer vary by region, squamous cell carcinoma and adenocarcinoma remain the two most common types, accounting for nearly 85% and 15% of all esophageal cancer cases, respectively. Most patients are diagnosed at an advanced stage, which impacts their daily lives, including their diet.

About Opdivo

Opdivo was approved in July 2014 as the world’s first PD-1 inhibitor and has since been approved in 66 countries and regions for a total of 11 tumor types.^[1], covering lung cancer, head and neck cancer, gastric cancer, esophageal cancer, liver cancer, renal cancer, colorectal cancer, urothelial carcinoma, melanoma, Hodgkin lymphoma, and pleural tumors, benefiting over 590,000 patients worldwide.

Opdivo is the first immuno-oncology drug approved for marketing in China. It currently has three approved indications in China; other indications, except those listed below, have not yet been approved:

Opdivo is the only PD-1 inhibitor directly developed with the involvement of a Nobel Laureate in Physiology or Medicine. Bristol-Myers Squibb holds the exclusive rights to Dr. Tasuku Honjo’s PD-1 patent.

[1] Note: Opdivo-based immune monotherapy and immune combination therapy regimens