FDA Grants Priority Review to 2 sBLAs for Nivolumab in the Treatment of Cancers of the Gastrointestinal Tract


Bristol Myers Squibb announced that nivolumab has been granted priority review for indications in both the first-line and adjuvant treatment settings as therapy for gastrointestinal cancers.

The FDA has accepted and granted priority review to the supplemental biologics license application (sBLA) for nivolumab (Opdivo) in combination with fluoropyrimidine- and platinum-containing chemotherapy for the treatment of patients with advanced or metastatic gastric or gastroesophageal junction (GEJ) cancers or esophageal adenocarcinoma (EAC), according to Bristol Myers Squibb, the developer of the agent.1

In addition, a second sBLA for nivolumab was granted priority review for the treatment of patients with resected esophageal or GEJ cancer in the adjuvant setting, following neoadjuvant chemoradiation therapy (CRT).2

Prescription drug user fee act (PDUFA) goal dates have been set by the FDA for May 25 and May 20, 2021, respectively.

The sBLA filing for the frontline indication was based on results from the pivotal, randomized, multi-center, open-label phase 3 CheckMate649 trial (NCT02872116), which is evaluating nivolumab plus either chemotherapy or ipilimumab (Yervoy) compared with chemotherapy alone in patients with previously untreated, advanced or metastatic gastric or GEJ cancer or EAC that is not positive for HER2 expression.

Patients in the nivolumab-plus-chemotherapy arm received nivolumab at a dose of 240 mg plus leucovorin, 5-fluorouracil, and oxaliplatin (FOLFOX) every 2 weeks or nivolumab at a dose of 360 mg plus capecitabine and oxaliplatin (CapeOX) every 3 weeks. Patients in the nivolumab-plus-ipilimumab arm received nivolumab at a dose of 1 mg/kg plus 3 mg/kg of ipilimumab every 3 weeks for 4 cycles followed by 240 mg of nivolumab every 2 weeks. Patients in the chemotherapy arm received FOLFOX or CapeOX every 2 or 3 weeks, respectively.

All study participants continued treatment for up to 2 years or until disease progression, unacceptable toxicity, or withdrawal of consent.

The dual primary end points for the trial are overall survival (OS) and progression-free survival (PFS), as assessed by blinded independent central review (BICR), for nivolumab plus chemotherapy compared with chemotherapy alone in patients with PD-L1–positive tumors indicated by a combined positive score (CPS) of 5 or greater. Key secondary end points also include OS in patient with a CPS of 1 or more and in all-randomized patients treated with nivolumab plus chemotherapy, as well as OS and time to symptom deterioration in patients treated with nivolumab plus ipilimumab compared with chemotherapy alone.

Thus far, the study has demonstrated that first-line treatment with nivolumab plus FOLFOX or CapeOX led to a statistically significant improvement in both primary end points.

“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 of gastrointestinal cancers at Bristol Myers Squibb, said in a press release. “The positive results of the CheckMate649 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.”

For its indication as therapy for early-stage disease, filing was based on results from the randomized, multi-center, double-blind, phase 3 CheckMate 577 trial (NCT02743494), which is evaluating nivolumab as adjuvant therapy for patients with resected esophageal or GEJ cancer who have received neoadjuvant CRT and have not achieved a pathological complete response.

The primary end point of the trial is disease-free survival (DFS) and the secondary end point is OS.

After neoadjuvant CRT and complete tumor surgical resection (trimodality therapy), a total of 794 patients were randomized to receive either placebo (n = 262) or nivolumab (n = 532) at a dose of 240 mg by intravenous infusion every 2 weeks for 16 weeks followed by placebo or 480 mg nivolumab every 4 weeks. Participants continued treatment until disease recurrence, unacceptable toxicity, or withdrawal of consent, with a maximum of 1-year total treatment duration.

Importantly, CheckMate 577 is the first trial to show positive results in the adjuvant setting in this patient population. The study met its primary end point of DFS and follow-up for OS remains ongoing.

Regarding safety, the safety profile of nivolumab as adjuvant therapy in the trial was found to be consistent with that reported in previous studies.

“The FDA’s acceptance of our application marks important progress toward our goal of advancing treatment options for patients with esophageal or gastroesophageal junction cancer, in this case in early-stage disease,” Waxman said in a separate press release. “We look forward to working with the FDA to potentially bring [nivolumab] to these patients, who face a critical unmet need and remain at high risk for disease recurrence.”


1. U.S. Food and Drug Administration Accepts for Priority Review Application for Opdivo® (nivolumab) Combined with Chemotherapy as First-Line Treatment in Metastatic Gastric Cancer, Gastroesophageal Junction Cancer and Esophageal Adenocarcinoma. News release. Princeton, New Jersey. Published January 20, 2021. Accessed January 20, 2021. https://news.bms.com/news/corporate-financial/2021/U.S.-Food-and-Drug-Administration-Accepts-for-Priority-Review-Application-for-Opdivo-nivolumab-Combined-with-Chemotherapy-as-First-Line-Treatment-in-Metastatic-Gastric-Cancer-Gastroesophageal-Junction-Cancer-and-Esophageal-Adenocarcinoma/default.aspx

2. U.S. Food and Drug Administration Accepts for Priority Review Application for Opdivo® (nivolumab) as Adjuvant Therapy for Patients with Resected Esophageal or Gastroesophageal Junction Cancer. News release. Princeton, New Jersey. Published January 20, 2021. Accessed January 20, 2021. https://news.bms.com/news/corporate-financial/2021/U.S.-Food-and-Drug-Administration-Accepts-for-Priority-Review-Application-for-Opdivo-nivolumab-as-Adjuvant-Therapy-for-Patients-with-Resected-Esophageal-or-Gastroesophageal-Junction-Cancer/default.aspx

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