January 20, 2021 - The FDA has granted a priority review to a supplemental biologics license application for nivolumab in combination with a fluoropyrimidine- and platinum-containing chemotherapy for use in patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma.
The FDA has granted a priority review to a supplemental biologics license application for nivolumab (Opdivo) in combination with a fluoropyrimidine- and platinum-containing chemotherapy for use in patients with advanced or metastatic gastric cancer, gastroesophageal junction (GEJ) cancer, or esophageal adenocarcinoma.1
The application was based on data from the phase 3 CheckMate-649 trial, which showed that nivolumab plus leucovorin, 5-fluorouracil, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CapeOX) significantly improved survival in treatment-naïve patients with PD-L1–positive advanced gastric cancer, GEJ cancer, and esophageal adenocarcinoma compared with chemotherapy alone.2
At a minimum follow-up of 12 months, the median overall survival (OS) with nivolumab/chemotherapy was 14.4 months (95% CI, 13.1-16.2) versus 11.1 months with chemotherapy alone (95% CI, 10-12.1) in patients who had a PD-L1 combined positive score (CPS) of 5 or greater (HR, 0.71; 98.4% CI, 0.59-0.86; P < .0001); this translated to a 29% reduction in the risk of death with nivolumab/chemotherapy. Moreover, the combination also reduced the risk of disease progression or death by 32% versus chemotherapy alone (HR, 0.68; 95% CI, 0.56-0.81; P <.0001).
Under the Prescription Drug User Fee Act, the FDA must make a decision by May 25, 2021.
“Today’s filing acceptance by the FDA marks important progress for the gastrointestinal cancer community and builds on our momentum of advancing immunotherapies to help improve the lives of those with advanced gastric and esophageal tumors,” Ian M. Waxman, MD, development lead, gastrointestinal cancers, at Bristol Myers Squibb, stated in a press release. “The positive results of the CheckMate-649 trial are potentially practice-changing, and we look forward to working with the FDA to possibly bring the first immunotherapy-based treatment option to front-line patients, for whom no novel therapies have been made available in the last decade.”
In the CheckMate-649 trial, total of 1581 participants were randomized in a 1:1 fashion to receive either nivolumab at a dose of 360 mg plus CapeOX every 3 weeks or nivolumab at a dose of 240 mg with FOLFOX every 2 weeks (n = 789) versus CapeOX or FOLFOX alone (n = 792). More than half of patients, or 60%, had a PD-L1 CPS of 5 or greater. The co-primary end points of the trial were OS and progression-free survival (PFS), while key secondary end points were OS in all randomized patients and those with a PD-L1 CPS of 1 or greater.
Additional results revealed that the median OS in the combination arm was 14 months in those with a PD-L1 CPS of 1 or greater compared with 11.3 months in the chemotherapy arm (HR, 0.77; 99.3% CI, 0.64-0.92; P = .0001). Moreover, the median OS with the combination versus chemotherapy alone was 13.8 months and 11.6 months, respectively, among all patients who underwent randomization (HR, 0.80; 99.3% CI, 0.68-0.94; P = .0002).
The safety profile of the nivolumab/chemotherapy combination was as expected, and no new signals were observed. Any-grade treatment-related toxicities reported in the subset of patients with a PD-L1 CPS of 5 or greater were reported in 95% of those on the investigational arm (n = 468) versus 88% of those on the control arm (n = 465). Grade 3 or 4 treatment-related adverse effects (TRAEs) occurred in 59% of those who received nivolumab/chemotherapy versus 44% of those who received chemotherapy alone.
More patients on the investigational arm discontinued treatment because of treatment-related toxicities compared with the control arm, at 38% versus 25%, respectively. Eight patients on the combination arm died because of a TRAE versus 4 patients on the chemotherapy arm.
The CheckMate-649 trial is also evaluating the combination of nivolumab plus ipilimumab (Yervoy); those in this arm were given nivolumab at a dose of 1 mg/kg plus ipilimumab at a dose of 3 mg/kg every 3 weeks for 4 cycles followed by nivolumab at a dose of 240 mg every 2 weeks. Data for this arm of the trial will be reported at an upcoming medical conference.