Bristol Myers Squibb (NYSE: BMY) today announced results from the Phase 3 CheckMate -648 trial, in which two Opdivo-based treatment combinations — Opdivo (nivolumab)plus chemotherapy and Opdivo plus Yervoy (ipilimumab) —demonstrated a statistically significant and clinically meaningful overall survival (OS) benefit compared to chemotherapy at the pre-specified interim analysis in patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC) with tumor cell PD-L1 expression ≥1%, as well as in the all-randomized population. Opdivo plus Yervoy is the first dual immunotherapy combination to demonstrate a superior survival benefit versus chemotherapy in this setting. The data will be presented in an oral session on Saturday, June 5, 2021 from 1:45 p.m. to 4:45 p.m. EDT and featured in the official press program during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.
For the combination of Opdivo plus chemotherapy, median OS was 15.4 months vs. 9.1 months for chemotherapy in patients whose tumors express PD-L1, a primary endpoint (hazard ratio [HR] 0.54, 99.5% CI: 0.37-0.80, p<0.0001), and 13.2 months vs. 10.7 months in the all-randomized patient population, a secondary endpoint (HR 0.74, 99.1% CI: 0.58-0.96, p=0.0021). A statistically significant progression-free survival (PFS) benefit was also observed with Opdivo plus chemotherapy in patients whose tumors express PD-L1, with a median PFS by blinded independent central review (BICR) of 6.9 months compared to 4.4 months with chemotherapy alone (HR 0.65, 98.5% CI: 0.46-0.92, p=0.0023).
For the combination of Opdivo plus Yervoy, median OS was 13.7 months vs. 9.1 months for chemotherapy in patients whose tumors express PD-L1, a primary endpoint (HR 0.64, 98.6% CI: 0.46-0.90, p=0.001), and 12.8 months vs. 10.7 months, respectively, in the all-randomized patient population, a secondary endpoint (HR 0.78, 98.2% CI: 0.62-0.98, p=0.011). Opdivo plus Yervoy did not meet its other primary endpoint of PFS by BICR in patients whose tumors express PD-L1 (4.0 months vs. 4.4 months; HR 1.02, 98.5% CI: 0.73-1.43, p=0.8958).
The safety profiles of Opdivo plus chemotherapy and Opdivo plus Yervoy were consistent with those previously reported for other tumor types. Grade 3/4 drug-related adverse events were 47% in the Opdivo plus chemotherapy arm, 32% in the Opdivo plus Yervoy arm, and 36% in the chemotherapy arm. The safety profile in patients with PD-L1 ≥1% was consistent with the all-randomized data.
“Patients with advanced esophageal squamous cell carcinoma face a median survival of around 10 months when treated with chemotherapy alone and there is a clear need for treatment options beyond this current standard of care,” said Ian Chau, M.D., Consultant Medical Oncologist, The Royal Marsden NHS Foundation Trust. “The data being presented at ASCO show that both of these nivolumab-based treatment options resulted in significant improvements in survival over chemotherapy and could offer potential new treatment options.”
The median duration of response (DoR) per BICR was 8.4 months for Opdivo plus chemotherapy, 11.8 months for Opdivo plus Yervoy, and 5.7 months for chemotherapy alone in patients whose tumors express PD-L1, and 8.2 months, 11.1, and 7.1 months, respectively, in the all-randomized population.
Opdivo plus chemotherapy also showed a clinically meaningful increase in objective response rate (ORR). The ORR per BICR was 53% for Opdivo plus chemotherapy, 35% for Opdivo plus Yervoy, and 20% for chemotherapy alone in patients whose tumors express PD-L1 and 47%, 28% and 27%, respectively, in the all-randomized population.
CheckMate –648 is the first global Phase 3 study to evaluate both an immunotherapy and chemotherapy combination as well as a dual immunotherapy combination in advanced ESCC.
“These data add to our growing body of evidence supporting the clinical benefit of Opdivo in upper GI cancers, from the late-line metastatic setting to earlier stages of disease,” said Ian M. Waxman, M.D., development lead, gastrointestinal cancers, Bristol Myers Squibb. “Opdivo has now demonstrated superior first-line efficacy in multiple upper GI cancers across histologies and tumor locations.”
About CheckMate -648
CheckMate -648 is a randomized Phase 3 study evaluating Opdivo plus Yervoy or Opdivo plus fluorouracil and cisplatin against fluorouracil plus cisplatin alone in patients with unresectable advanced or metastatic esophageal squamous cell carcinoma.
The primary endpoints of the trial are overall survival (OS) and progression-free survival (PFS) by blinded independent central review (BICR) in patients whose tumors express PD-L1 ≥1% for both Opdivo-based combinations versus chemotherapy. Secondary endpoints of the trial include OS and PFS by BICR in the all-randomized population.
In the Opdivo plus chemotherapy arm (N=321), patients received treatment with Opdivo 240 mg on Day 1 and Day 15, fluorouracil 800 mg/m²/day on Day 1 through Day 5 (for 5 days), and cisplatin 80 mg/m² on Day 1 of four-week cycle. Patients received Opdivo for up to 24 months or until disease progression or unacceptable toxicity, and chemotherapy until disease progression or unacceptable toxicity.
In the Opdivo plus Yervoy arm (N=325), patients received treatment with Opdivo 3 mg/kg every 2 weeks and Yervoy 1 mg/kg every 6 weeks up to 24 months or until disease progression or unacceptable toxicity.
About Esophageal Cancer
Esophageal cancer is the eighth most common cancer and the sixth leading cause of death from cancer worldwide, with approximately 604,000 new cases and over 544,000 deaths in 2020. The two most common types of esophageal cancer are squamous cell carcinoma (ESCC) and adenocarcinoma, which account for approximately 90% and 10% of all esophageal cancers, respectively, though esophageal tumor histology can vary by region. The overall burden of ESCC is concentrated in Asia, where roughly 80% of the global cases occurred in 2020. The majority of esophageal cancer cases are diagnosed in the advanced setting and impact a patient’s daily life, including their ability to eat and drink. ESCC occurs most often in the upper and middle portions of the esophagus, whereas adenocarcinoma begins in the cells of mucus-secreting glands in the esophagus and most often occurs in the lower portion of the esophagus.
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.
Read the Full Release Here