AstraZeneca Gains Nod from FDA for Perioperative Imfinzi-Based Regimen
The regulator’s decision will provide a new clinical option for patients with early gastric and gastroesophageal cancers that can deliver a significant survival benefit versus chemotherapy alone.
FDA has approved the combination regimen of durvalumab (Imfinzi, AstraZeneca) with fluorouracil, leucovorin oxaliplatin, and docetaxel (FLOT) chemotherapy as a treatment for patients with early gastric and gastroesophageal cancers (1). The approval follows FDA’s Priority Review of the regimen, which comprises neoadjuvant durvalumab in combination with chemotherapy before surgery, followed by adjuvant durvalumab in combination with chemotherapy, and then durvalumab as monotherapy.
Durvalumab is a human monoclonal antibody that works by binding to the PD-L1 protein and blocking the interaction of PD-L1 with the PD-1 and CD80 proteins, which counteracts the tumor’s immune-evading tactics and releasing the inhibition of immune responses.
“This approval ushers in a new clinical paradigm for patients with early gastric and gastroesophageal junction cancers, with Imfinzi plus FLOT delivering a durable survival benefit that increases over time,” said Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, in a company press release (1). “As the third U.S. approval for a perioperative Imfinzi-based regimen, this milestone further validates the perioperative approach and underscores our focus on bringing novel treatments to early-stage cancers where cure is the goal.”
The regulator’s decision has been based on the positive results of the MATTERHORN Phase III trial aimed at evaluating durvalumab as perioperative treatment for patients with resectable Stage II-IVA gastric and gastroesophageal junction (GEJ) cancers. The randomized, double-blind, placebo-controlled, multi-centre, global Phase III trial demonstrated a 29% reduction in the risk of progression, recurrence, or death, and a 22% reduction in the risk of death for the treatment regimen versus chemotherapy alone (1).
“[This] approval marks the first immunotherapy regimen approved in the neoadjuvant setting for gastric and gastroesophageal junction cancers — with durvalumab demonstrating a clear overall survival benefit and opening an entirely new chapter in the treatment of early-stage disease,” added Yelena Y. Janjigian, MD, Chief Attending Physician of the Gastrointestinal Medical Oncology Service, Memorial Sloan Kettering Cancer Center (MSK), New York and principal investigator in the MATTERHORN trial, in the press release (1). “Nearly seven in 10 patients were alive at three years following treatment with the durvalumab-based perioperative regimen. This survival benefit, observed regardless of PD-L1 status, establishes a new standard of care in this curative-intent setting.”
Safety of the combination regimen was found to be consistent with the known profiles of each separate medicine and the proportion of patients who completed surgery was similar compared with the chemotherapy alone arm. Incidence of grade 3 or higher adverse events was similar between the two arms of the trial.
The combination regimen is also under regulatory consideration in Australia, Canada, and Switzerland for the same indication as the U.S. Other regulatory applications are under review in the European Union, Japan, and several other countries.
Reference
AstraZeneca. Imfinzi Approved in the US as First and Only Perioperative Immunotherapy for Patients with Early Gastric and Gastroesophageal Cancers. Press Release, Nov. 21, 2025.