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Results from the Phase III MATTERHORN trial (NCT04592913) found that perioperative treatment with Imfinzi (durvalumab) plus a chemotherapy regimen comprised of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) produced a significant improvement in event-free survival (EFS) among patients with resectable gastric and gastroesophageal junction (GEJ) cancer.1,2 These findings follow data from the trial released in October 2023 showing a statistically significant and clinically meaningful improvement in pathologic complete response (pCR) with the combination compared to neoadjuvant chemotherapy alone in this patient population.3
“Despite receiving curative-intent chemotherapy and surgery, patients with gastric cancer commonly face disease recurrence and have a poor prognosis,” principal trial investigator Yelena Y Janjigian, MD, chief attending physician of the Gastrointestinal Medical Oncology Service, Memorial Sloan Kettering Cancer Center, New York, said in a press release. “These exciting data from MATTERHORN show that a durvalumab-based perioperative regimen resulted in a clinically meaningful improvement in patient outcomes, including decreasing the risk of the cancer coming back.”1
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.
Trial Design
The randomized, double-blind, placebo-controlled, multi-center, global MATTERHORN trial analyzed neoadjuvant administration of Imfinzi plus FLOT in patients with resectable stage II-IVA gastric and GEJ cancers. Participants were enrolled at 176 centers across 20 countries, including the United States, Canada, Europe, South America, and Asia.
Investigators randomly assigned 948 patients to receive Imfinzi at a fixed dose of 1500 mg plus FLOT chemotherapy or placebo plus FLOT chemotherapy administered every four weeks for two cycles before surgery. The regimen was followed by Imfinzi or placebo administered every four weeks for up to 12 cycles following surgery. The trial’s primary endpoint was EFS, with key secondary endpoints that included pCR rate and overall survival (OS).
Results showed a statistically significant and clinically meaningful improvement in EFS, achieving the trial’s primary endpoint. Prior data released from the trial showed a pCR rate of 19% with the Imfinzi combination compared to 7% with chemotherapy alone as determined by blinded independent central review (odds ratio [OR] 3.08; p<0.00001). Rates of either complete or near-complete responses were 27% in patients treated with the Imfinzi combination compared to 14% with chemotherapy alone.3
Data also showed a strong trend favoring the Imfinzi combination at the time of the interim analysis. In terms of safety, the profile of Imfinzi and FLOT chemotherapy was consistent with prior findings and now no new safety signals were reported. Full data from the trial will be presented at an upcoming medical meeting and shared with global regulatory authorities.
“MATTERHORN is the first Phase III trial of an immunotherapy to show a statistically significant improvement in event-free survival in patients with resectable gastric and gastroesophageal junction cancers,” said Cristian Massacesi, chief medical officer and oncology chief development officer, AstraZeneca, in a press release. “This perioperative approach with Imfinzi underscores our commitment to moving into earlier stages of cancer where novel therapies can have the biggest impact on patients’ lives.”1
References
1. Imfinzi-based regimen demonstrated statistically significant and clinically meaningful improvement in event-free survival in resectable early-stage gastric and gastroesophageal junction cancers. News release. AstraZeneca. March 7, 2025. Accessed March 7, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/imfinzi-improved-efs-in-early-stage-gastric-cancer.html
2. Assessing Durvalumab and FLOT Chemotherapy in Resectable Gastric and Gastroesophageal Junction Cancer. ClinicalTrials.gov. December 13, 2024. Accessed March 7, 2025. https://clinicaltrials.gov/study/NCT04592913
3. Imfinzi plus chemotherapy more than doubled pathologic complete response rate in resectable early-stage gastric and gastroesophageal junction cancers versus chemotherapy alone. News release. AstraZeneca. October 20, 2023. Accessed March 7, 2025. https://www.astrazeneca.com/media-centre/press-releases/2023/imfinzi-plus-chemotherapy-doubled-pathologic-complete-response-rate-resectable-early-stage-gastric-gastroesophageal-junction-cancers-vs-chemotherapy.html