The US Food and Drug Administration (FDA) has approved AstraZeneca’s Imfinzi (durvalumab) combined with standard-of-care FLOT chemotherapy for adults with resectable, early-stage and locally advanced gastric and gastroesophageal junction (GEJ) cancers (Stages II, III, IVA). The treatment plan includes neoadjuvant Imfinzi with chemotherapy before surgery, followed by adjuvant Imfinzi with chemotherapy and then Imfinzi monotherapy.
Approval Based on MATTERHORN Phase III Trial Results
This approval follows a Priority Review and is supported by compelling event-free survival (EFS) and overall survival (OS) results from the Phase III MATTERHORN trial. The EFS findings were presented during the Plenary Session at the 2025 ASCO Annual Meeting and published in The New England Journal of Medicine. The researchers shared OS results at the 2025 ESMO Congress.
Gastric cancer remains the fifth leading cause of cancer-related deaths globally, with one million new cases annually. In the US alone, roughly 6,500 patients received drug treatment for early-stage or locally advanced disease in 2024.
Researchers and Experts Highlight a New Treatment Paradigm
Dave Fredrickson, Executive Vice President of AstraZeneca’s Oncology Haematology Business Unit, stated that the approval introduces a new clinical paradigm. He added that it offers durable and improving survival benefits over time. Dr. Yelena Janjigian of Memorial Sloan Kettering Cancer Center, the trial’s principal investigator, emphasised that this is the first approved immunotherapy regimen in the neoadjuvant setting for these cancers. She noted it delivers clear overall survival benefits regardless of PD-L1 status.
Patient advocate Aki Smith added that the decision brings renewed hope to families affected by this aggressive disease.
Significant Survival Benefits Demonstrated
Interim trial data showed a 29% reduction in the risk of disease progression, recurrence, or death with the Imfinzi-based perioperative regimen (HR 0.71; p<0.001). Final OS results revealed a 22% reduction in mortality risk (HR 0.78; p=0.021), with 69% of patients alive at three years versus 62% receiving chemotherapy alone.
Global Regulatory Reviews Underway
According to the AstraZeneca press release, AstraZeneca reviewed the regimen under Project Orbis, enabling parallel evaluations in multiple countries. Regulatory reviews are ongoing in Australia, Canada, Switzerland, the EU, Japan, and other regions.