AstraZeneca’s IMFINZI (durvalumab) in combination with standard-of-care FLOT chemotherapy (fluorouracil, leucovorin, oxaliplatin, and docetaxel) has been approved in the U.S. for the treatment of adult patients with resectable, early-stage and locally advanced (Stages II, III, IVA) gastric and gastroesophageal junction (GEJ) cancers. The approved regimen includes neoadjuvant IMFINZI in combination with chemotherapy before surgery, followed by adjuvant IMFINZI in combination with chemotherapy, then IMFINZI monotherapy.

The approval, granted under Priority Review, is based on Phase III MATTERHORN trial data showing improvements in event-free survival (EFS) and overall survival (OS). EFS results were published in The New England Journal of Medicine.

Dave Fredrickson, Executive Vice President of AstraZeneca’s Oncology Haematology Business Unit, said: “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. 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.”

In an interim analysis, the IMFINZI-based regimen reduced the risk of disease progression, recurrence or death by 29% versus chemotherapy alone (HR 0.71; 95% CI 0.58-0.86; P<0.001). Median EFS was not reached for the IMFINZI arm versus 32.8 months for the comparator. At one year, 78.2% of patients on the IMFINZI regimen were event-free compared to 74.0% on chemotherapy alone; at two years, rates were 67.4% versus 58.5%.

Final OS analysis showed a 22% reduction in risk of death (HR 0.78; 95% CI 0.63-0.96; P=0.021), with three-year survival at 69% for IMFINZI versus 62% for FLOT alone. Benefit was observed regardless of PD-L1 status.

Safety was consistent with known profiles, and surgery completion rates were similar between arms. Grade 3 or higher adverse events occurred in 71.6% of patients on IMFINZI plus FLOT and 71.2% on FLOT alone.

The submission was reviewed under Project Orbis, enabling parallel regulatory reviews in Australia, Canada and Switzerland. Applications are also under review in the EU, Japan and other markets.