Bristol Myers Squibb announced that the U.S. Food and Drug Administration (FDA) has accepted the supplemental Biologics License Applications (sBLA) for both Opdivo® (nivolumab) in combination with Yervoy (ipilimumab) and Opdivo in combination with fluoropyrimidine- and platinum-containing chemotherapy as first-line treatments for adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC), based on results from the CheckMate -648 trial. The FDA assigned a Prescription Drug User Fee Act (PDUFA) goal date of May 28, 2022. The filings were based on results from the pivotal Phase 3 CheckMate -648 trial, marking the fourth global trial in which Opdivo or Opdivo-based treatment combinations demonstrated a significant benefit for patients with upper gastrointestinal cancers. In CheckMate -648, both Opdivo-based treatment combinations — Opdivo plus Yervoy and Opdivo plus chemotherapy — demonstrated a statistically significant and clinically meaningful overall survival (OS) benefit compared to chemotherapy in patients with unresectable advanced or metastatic 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 safety profiles of Opdivo plus Yervoy and Opdivo plus chemotherapy were consistent with the known safety profiles of the individual components. 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 Yervoy arm, 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. In the Opdivo plus chemotherapy arm, 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.