Research & Development
Bristol Myers Squibb Receives Positive CHMP Opinion for Opdivo + Chemotherapy for Patients with HER2-Negative Advanced or Metastatic Gastric, Gastroesophageal Junction or Esophageal Adenocarcinoma whose Tumors Express PD-L1 with CPS ≥ 5
20 September 2021 - - The Committee for Medicinal Products for Human Use of the European Medicines Agency has recommended approval of Opdivo (nivolumab) in combination with fluoropyrimidine and platinum-containing chemotherapy for the first-line treatment of adult patients with HER2-negative advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma whose tumors express PD-L1 with a combined positive score ≥ 5, US-based Bristol Myers Squibb (NYSE: BMY) said.

The European Commission, which has the authority to approve medicines for the European Union, will now review the CHMP recommendation.

The positive opinion is based on results from the pivotal Phase 3 CheckMate -649 trial, in which first-line treatment with Opdivo plus leucovorin, 5-fluorouracil and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CapeOX) was compared to treatment with chemotherapy alone.

Results showed a statistically significant and clinically meaningful improvement in overall survival and progression-free survival in patients with unresectable advanced or metastatic GC, GEJ cancer or EAC whose tumors express PD-L1 with a combined positive score ≥ 5 (the primary endpoints of the study).

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.

The safety profile observed for Opdivo plus chemotherapy in the CheckMate -649 trial was consistent with the known safety profiles of the individual treatments.

Expanded analysis from CheckMate -649 were presented during the 2021 American Society of Clinical Oncology annual meeting.

Opdivo in combination with fluoropyrimidine- and platinum-containing chemotherapy is approved in the United States for the treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma, regardless of PD-L1 expression status.

Checkmate -649 is a Phase 3 randomized, multi-center, open-label study evaluating Opdivo plus chemotherapy or the Opdivo plus Yervoy combination compared to chemotherapy alone in patients with previously untreated, non-HER2-positive, advanced or metastatic gastric cancer, gastroesophageal junction cancer or esophageal adenocarcinoma.

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.

The primary endpoints of the trial are overall survival in PD-L1 positive patients with a combined positive score ≥ 5 treated with Opdivo plus chemotherapy and PFS, as assessed by Blinded Independent Central Review, in CPS ≥ 5 patients treated with Opdivo plus chemotherapy compared to chemotherapy alone.

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 in patients treated with Opdivo plus Yervoy compared to chemotherapy alone.

Gastric cancer, also known as stomach cancer, is the fifth most common cancer and the fourth leading cause of cancer death worldwide, with over 1m new cases and approximately 770,000 deaths in 2020.

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 distal gastric cancer, it continues to rise.

Esophageal cancer is the eighth most common cancer and the sixth leading cause of death from cancer worldwide, with approximately 600,000 new cases and over 540,000 deaths in 2020.

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 and Europe.


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