Phase III MATTERHORN Trial Shows Imfinzi Combo Significantly Improves Event-Free Survival in Resectable Gastric and GEJ Cancers

Key Takeaways

First Immunotherapy to Achieve Statistically Significant EFS in Resectable Gastric and GEJ Cancers. Imfinzi (durvalumab) combined with FLOT chemotherapy significantly improved event-free survival (EFS) versus chemotherapy alone in resectable Stage II–IVA gastric and gastroesophageal junction (GEJ) cancers, becoming the first immunotherapy to reach this milestone in a global Phase III trial.
Durable Two-Year EFS and Strong Trend Toward OS Benefit. The Imfinzi-based perioperative regimen achieved a two-year EFS rate of 67.4% versus 58.5% with FLOT alone. Although overall survival results have not yet met statistical significance, a favorable trend is emerging, particularly beyond 12 months of follow-up.
Consistent Safety Profile and Global Applicability. Adverse events and surgical outcomes were comparable between study arms, with no major delays in treatment initiation. The trial’s global scope across 20 countries supports the regimen’s potential broad applicability in clinical practice worldwide.

Results from a planned interim analysis of the pivotal Phase III MATTERHORN trial (NCT04592913) show Imfinzi (durvalumab) plus standard-of-care chemotherapy produced a significant boost in event-free survival (EFS) among patients with resectable gastric and gastroesophageal junction (GEJ) cancers.^1,2

MATTERHORN Trial Establishes First EFS Benefit with Immunotherapy in Resectable Gastric and GEJ Cancers

Trial data, presented at ASCO 2025 and published in The New England Journal of Medicine (NEJM), demonstrate that Imfinzi is the first immunotherapy to achieve statistically significant EFS in a global Phase III trial in this patient population, according to the trial investigators.³

“Despite receiving curative-intent surgery and chemotherapy, patients with gastric and gastroesophageal cancers frequently develop recurrent disease,” MATTERHORN principal investigator Yelena Y. Janjigian, MD, chief attending physician of Gastrointestinal Medical Oncology Service, Memorial Sloan Kettering Cancer Center, New York, said in a press release. “Despite receiving curative-intent surgery and chemotherapy, patients with gastric and gastroesophageal cancers frequently develop recurrent disease. Results from the MATTERHORN trial showed that more than two-thirds of patients treated with a durvalumab-based perioperative regimen had not experienced a recurrence or were progression-free after two years. This new treatment approach should become the new standard of care in this setting based on these results.”¹

Key Efficacy Outcomes: Event-Free Survival and Overall Survival Trends

Imfinzi is a selective, high-affinity human IgG1 monoclonal antibody that attaches to PD-L1 and blocks interactions with PD-1 and CD80 on activated T cells. Current FDA-approved indications for Imfinzi include for the treatment of unresectable, stage III non-small cell lung cancer (NSCLC) in patients with disease that has not progressed following chemoradiation therapy; for the treatment of extensive-stage small-cell lung cancer; combined with a limited course of Imjudo (tremelimumab) and chemotherapy to treat metastatic NSCLC; in combination with gemcitabine plus cisplatin to treat locally advanced or metastatic biliary tract cancer; and in combination with Imjudo to treat unresectable hepatocellular carcinoma. Most recently, Imfinzi was approved in combination with chemotherapy for adult patients with resectable early-stage (IIA-IIIB) NSCLC without EGFR mutations or ALK rearrangements.

“The FLOT4 trial established perioperative FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) as treatment for locally advanced resectable gastric or gastroesophageal junction adenocarcinoma; FLOT was associated with better overall survival and disease-free survival outcomes than epirubicin and cisplatin plus either fluorouracil or capecitabine,” the study authors wrote in NEJM. “Despite this result, recurrence rates with FLOT remain high. The combination of anti–programmed death ligand 1 (PD-L1) therapy and chemotherapy has shown encouraging outcomes and is approved for the treatment of metastatic gastric and gastroesophageal junction adenocarcinomas. Durvalumab, an anti–PD-L1 antibody, is approved for the treatment of a range of solid tumors.”³

Study Design and Global Scope of the Phase III MATTERHORN Trial

Imfinzi Plus FLOT Chemotherapy Significantly Improves Event-Free Survival in Resectable Gastric and GEJ Cancers

Durability of Response and Safety Profile Across Treatment Arms

Global Relevance and Future Impact on Perioperative Treatment Standards

“A key strength of the MATTERHORN trial was its global reach, which reflected the global population with gastric or gastroesophageal junction adenocarcinoma eligible for perioperative FLOT, including participants across Europe, the Americas, and East Asia with stage II to IVA disease,” the study authors wrote. “Of note, the median event-free survival in the placebo group of the MATTERHORN trial (32.8 months) was consistent with the median disease-free survival in the FLOT group of the FLOT4 trial (30 months). Recent studies suggest that event-free survival is a good surrogate end point for overall survival in patients with gastric or gastroesophageal junction adenocarcinoma in the context of neoadjuvant therapy with or without adjuvant therapy.”³

2. Assessing Durvalumab and FLOT Chemotherapy in Resectable Gastric and Gastroesophageal Junction Cancer. ClinicalTrials.gov. Updated April 3, 2025. Accessed June 4, 2025. https://clinicaltrials.gov/study/NCT04592913

3. Janjigian Y., et al. N Engl J Med 2025; Perioperative Durvalumab in Gastric and Gastroesophageal Junction Cancer. DOI: 10.1056/NEJMoa2503701.