On November 25, 2025, the U.S. Food and Drug Administration (FDA) approved durvalumab (Imfinzi) in combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy as neoadjuvant and adjuvant treatment, followed by single-agent durvalumab, for the treatment of adult patients with resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Efficacy for the combination was evaluated in the randomized, double-blind, placebo-controlled, multicenter MATTERHORN trial (ClinicalTrials.gov identifier NCT04592913), which enrolled 948 patients with previously untreated and resectable stage II to stage IVA gastric/GEJ adenocarcinoma. All patients were randomly assigned (1:1) to receive either durvalumab plus FLOT or placebo plus FLOT.
The primary efficacy outcome measure was event-free survival by blinded independent central review assessment. Additional efficacy outcome measures were overall survival and pathologic complete response rate, both assessed by blinded central pathology review. The trial was not designed to isolate the effect of durvalumab in each phase (neoadjuvant or adjuvant) of treatment.
The median event-free survival was not reached (95% confidence interval [CI] = 40.7 to not evaluable) in the durvalumab plus FLOT arm and was 32.8 months (95% CI = 27.9 to not evaluable) in the placebo plus FLOT arm (hazard ratio [HR] = 0.71; 95% CI = 0.58–0.86; P < .001). The median overall survival was not reached in either arm (HR = 0.78; 95% CI = 0.63–0.96; P = .021). The pathologic complete response rate was 19.2% (95% CI = 15.7%–23.0%) in the arm with added durvalumab and 7.2% (95% CI = 5.0%–9.9%) in the arm without durvalumab (P < .001).
The prescribing information for durvalumab includes warnings and precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.
The recommended dose for durvalumab in patients with a body weight of ≥ 30 kg is 1,500 mg every 4 weeks with chemotherapy for up to 4 cycles (neoadjuvant and adjuvant treatment), followed by 1,500 mg as a single agent every 4 weeks for up to 10 cycles (adjuvant treatment). The recommended durvalumab dose for patients with a body weight < 30 kg is 20 mg/kg with chemotherapy every 4 weeks for up to 4 cycles (neoadjuvant and adjuvant treatment) and 20 mg/kg as a single agent every 4 weeks for up to 10 cycles (adjuvant treatment). Treatment should be continued until disease progression, recurrence, or unacceptable toxicity, or a maximum of 12 cycles after surgery.
Review for this indication was conducted under Project Orbis through collaboration with international partners: Australian Therapeutic Goods Administration (TGA), the Brazilian Health Regulatory Agency (ANVISA), Health Canada (HC), Israel’s Ministry of Health (ImoH), and Switzerland’s Swissmedic (SMS). Reviews for this application are ongoing at the other regulatory agencies.
This application was granted a Priority Review designation and durvalumab has received Breakthrough Therapy and Orphan Drug designations.
