FDA Approves Imfinzi Plus FLOT for Early and Locally Advanced Gastric and GEJ Cancers

The FDA has approved AstraZeneca’s Imfinzi (durvalumab) in combination with standard-of-care FLOT chemotherapy (fluorouracil, leucovorin, oxaliplatin, and docetaxel) for the treatment of adult patients with resectable, early-stage and locally advanced (Stages II, III, IVA) gastric and gastroesophageal junction (GEJ) cancers.¹

The approved regimen includes:

• Neoadjuvant Imfinzi in combination with chemotherapy prior to surgery
• Adjuvant Imfinzi in combination with chemotherapy
• Imfinzi monotherapy

In a press release, Dave Fredrickson, executive vice president, oncology hematology 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.”

Approval based on positive Phase III MATTERHORN data

Imfinzi’s approval is based on positive data from the Phase III MATTERHORN clinical trial (NCT04592913). Results shared earlier in October demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) compared to chemotherapy alone.²

Additional findings from the final OS analysis showed:

• Imfinzi plus FLOT perioperative regimen reduced the risk of death by 22% versus chemotherapy alone (HR 0.78; 95% CI: 0.63–0.96; P=0.021).
• Median OS was not reached in either treatment arm.
• At three years, estimated survival was 69% with the Imfinzi-based regimen compared with 62% for FLOT alone.

In the press release, 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, added: “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.”

MATTERHORN trial design

The MATTERHORN trial is a randomized, double-blind, placebo-controlled, multi-center, global study evaluating Imfinzi as perioperative therapy in resectable Stage II-IVA gastric and GEJ cancers.

• Perioperative treatment included both neoadjuvant and adjuvant therapy.
• A total of 948 patients were randomized to receive Imfinzi 1500 mg plus FLOT chemotherapy or placebo plus FLOT every four weeks for two cycles before surgery.
• Following surgery, patients received Imfinzi or placebo every four weeks for up to 12 cycles, including two cycles with FLOT chemotherapy and 10 cycles as monotherapy.
• The trial’s primary endpoint was event-free survival, with key secondary endpoints including pathologic complete response rate and OS.

A paradigm shift in gastric and GEJ cancer care

Following AstraZeneca’s announcement of positive results from MATTERHORN, Applied Clinical Trials spoke with Nancy Ghattas, VP, US oncology commercial franchise head of immuno-oncology.

“For the last 20 years, there’s been no major advancement in this space beyond surgery and chemotherapy—and that has been associated with poor prognosis as well. Patients tend to relapse within the first two years, and only about one out of four survive beyond five years, so there has been a huge unmet need,” Ghattas told ACT. “Now, with the MATTERHORN data, we’ve seen that when we start with Imfinzi—or an IO—in a perioperative setting, which basically means adding immunotherapy to chemotherapy before and after surgery, with maintenance immunotherapy afterward, we are seeing a meaningful change: an overall survival benefit of 22%.”

References

1. IMFINZI® approved in the US as first and only perioperative immunotherapy for patients with early gastric and gastroesophageal cancers. News release. AstraZeneca. November 25, 2025. Accessed November 26, 2025. https://www.astrazeneca-us.com/content/az-us/media/press-releases/2025/IMFINZI-approved-in-the-US-as-first-and-only-perioperative-immunotherapy-for-patients-with-early-gastric-and-gastroesophageal-cancers.html

2. Imfinzi Plus FLOT Significantly Improves Overall Survival in Gastric and Gastroesophageal Cancer. Applied Clinical Trials. October 17, 2025. Accessed November 26, 2025. https://www.appliedclinicaltrialsonline.com/view/imfinzi-flot-significantly-improves-overall-survival-gastric-gastroesophageal-cancer