FDA approves durvalumab for resectable gastric or gastroesophageal junction adenocarcinoma

Regulatory approval: On Nov 25, 2025, the FDA approved durvalumab (Imfinzi) with perioperative FLOT chemotherapy as neoadjuvant and adjuvant therapy, followed by durvalumab monotherapy, for adults with resectable gastric or gastroesophageal junction adenocarcinoma. Approval was supported by the phase 3 MATTERHORN trial (NCT04592913), which showed improved event-free survival versus placebo + FLOT (HR 0.71; p<0.001), with overall survival data immature (median not reached in both arms; HR 0.78).

FDA approval (Nov 25, 2025): Durvalumab for resectable GC/GEJC

The US FDA approved durvalumab (Imfinzi; AstraZeneca) in combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) as neoadjuvant and adjuvant treatment, followed by single-agent durvalumab, for adults with resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJC).

Supporting evidence

Efficacy was evaluated in MATTERHORN (NCT04592913), a randomized, double-blind, placebo-controlled, multicenter trial in 948 patients with previously untreated, resectable Stage II–IVA GC/GEJC, randomized 1:1 to durvalumab + FLOT vs placebo + FLOT.

  • Primary endpoint (EFS, BICR): median EFS not reached (95% CI 40.7–NE) with durvalumab + FLOT vs 32.8 months (95% CI 27.9–NE) with placebo + FLOT; HR 0.71 (95% CI 0.58–0.86); p<0.001.
  • OS: median OS not reached in both arms; HR 0.78 (95% CI 0.63–0.96); p=0.021.
  • pCR: 19.2% vs 7.2% (p<0.001).

The trial was not designed to isolate durvalumab’s effect by treatment phase (neoadjuvant vs adjuvant).

Label safety highlights

Warnings/precautions include immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic HSCT, and embryo-fetal toxicity.

Dosing (label)

  • ≥30 kg: 1,500 mg q4w with chemotherapy up to 4 cycles, then 1,500 mg q4w monotherapy up to 10 cycles.
  • <30 kg: 20 mg/kg q4w on the same schedule. Maximum: 12 cycles after surgery, or until progression/recurrence or unacceptable toxicity.

Regulatory context

Review used Project Orbis with other agencies’ reviews ongoing; the application received priority review, and durvalumab had breakthrough and orphan drug designations.

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