AstraZeneca’s Imfinzi (durvalumab), combined with standard-of-care FLOT chemotherapy (fluorouracil, leucovorin, oxaliplatin and docetaxel), has been approved in the US for adults with resectable, early-stage and locally advanced (Stages II, III, IVA) gastric and gastroesophageal junction (GEJ) cancers. The regimen includes neoadjuvant Imfinzi with chemotherapy before surgery, followed by adjuvant Imfinzi with chemotherapy and then Imfinzi monotherapy.
The approval, granted Priority Review by the US Food and Drug Administration (FDA), is based on results from the Phase III MATTERHORN trial. Event-free survival (EFS) data were presented during the Plenary Session at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and published in The New England Journal of Medicine. Overall survival (OS) findings were shared at the 2025 European Society for Medical Oncology (ESMO) Congress.
Gastric cancer is the fifth leading cause of cancer death worldwide, with nearly one million new cases annually. In the US, approximately 6,500 drug-treated patients were recorded in 2024 with early-stage or locally advanced gastric or GEJ cancer.
Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, 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 US 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.”
Yelena Y. Janjigian, MD, Chief Attending Physician at Memorial Sloan Kettering Cancer Center and principal investigator of MATTERHORN, said: “Today’s 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. 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.”
Aki Smith, Founder and Executive Director of Hope for Stomach Cancer, added: “From personal experience as a caregiver to my father, I know that for too long patients diagnosed with early gastric or gastroesophageal junction cancer have faced a high risk of their cancer returning, even after undergoing surgery and therapy intended to cure it. Today’s approval represents a major step forward in improving outcomes and offering renewed hope to those affected by this devastating disease.”
Interim MATTERHORN results showed a 29% reduction in the risk of disease progression, recurrence or death (EFS HR 0.71; 95% CI 0.58–0.86; p<0.001), while final OS data demonstrated a 22% reduction in the risk of death (HR 0.78; 95% CI 0.63–0.96; p=0.021). Safety outcomes were consistent with known profiles, and surgery completion rates were comparable. The submission was reviewed under Project Orbis, with parallel regulatory reviews ongoing in multiple countries.
