FDA Grants Priority Review to Perioperative Durvalumab in Resectable Gastric/GEJ Cancer

The FDA has granted priority review to a supplemental biologics license application (sBLA) seeking the approval of durvalumab (Imfinzi) for the treatment of patients with resectable, early-stage, locally advanced gastric and gastroesophageal junction (GEJ) cancers.1 Additionally, the FDA granted breakthrough therapy designation to durvalumab in this setting.

Notably, the Prescription Drug User Fee Act date is anticipated during the fourth quarter of 2025.

The sBLA was supported by data from the phase 3 MATTERHORN trial (NCT04592913), which evaluated the efficacy of neoadjuvant durvalumab plus FLOT (fluorouracil, leucovorin, oxaliplatin, docetaxel), followed by adjuvant durvalumab plus FLOT and durvalumab monotherapy.

The planned interim analysis presented at the 2025 ASCO Annual Meeting revealed that patients treated with the perioperative durvalumab-based regimen demonstrated a 29% reduction in the risk of disease progression, recurrence, or death compared with FLOT alone (HR, 0.71; 95% CI, 0.58-0.86; P < .001). Of note, the median event-free survival (EFS) was not reached (NR; 95% CI, 40.7-NR) in the durvalumab arm vs 32.8 months (95% CI, 27.9-NR) in the FLOT arm.2 The estimated 1-year EFS rates were 78.2% and 74.0%, respectively; the estimated 24-month EFS rates were 67.4% vs 58.5% in the respective arms.1

“This priority review reinforces the potential for a perioperative approach with durvalumab to transform care for patients with early gastric and [GEJ] cancers, who frequently face disease recurrence or progression even after curative-intent surgery and perioperative chemotherapy,” Susan Galbraith, executive vice president of oncology research and development at AstraZeneca, stated in a news release. “This novel treatment is the only immunotherapy-based regimen to show a statistically significant reduction in the risk of progression, recurrence or death in this setting, and if approved, is poised to change the clinical paradigm.”

MATTERHORN Trial Design

The global, randomized, double-blind, placebo-controlled study included patients 18 years and older with histologically documented gastric or GEJ adenocarcinoma with resectable disease that was stage II or higher (per American Joint Committee on Cancer 8th edition) who were eligible for radical surgery.3 An ECOG performance status of 0 or 1 at enrollment and no prior anticancer therapy for the current malignancy also were required. Furthermore, patients were expected to have adequate organ and marrow function, availability of a tumor sample before entering the study, and a life expectancy of 24 weeks or more.

Patients were not included in the study if they had peritoneal dissemination or distant metastasis; adenosquamous cell carcinoma, squamous cell carcinoma, or gastrointestinal stromal tumor; current or prior use of immunosuppressive medication within 14 days before the initial dose of durvalumab; contraindication of any of the respective drugs; or a history of allogeneic organ transplantation.

Patients were randomly assigned 1:1 to receive duravlumab at a dosing level of 1500 mg (n = 474) or placebo every 4 weeks (n = 474) plus FLOT for 4 cycles, of which 2 cycles each were in the neoadjuvant and adjuvant settings.4 This was followed by durvalumab or placebo every 4 weeks for 10 cycles.

The primary end point was EFS; the secondary end points included overall survival (OS) and pathologic complete response (pCR) rate.

Additional Efficacy and Safety Data

At 2 years, the OS rates were 75.7% in the durvalumab arm and 70.4% in the placebo arm (HR, 0.67; 95% CI, 0.50-0.90; P = .03). Additionally, in the durvalumab arm, the pCR rate was 19.2% compared with 7.2% in the placebo arm (relative risk, 2.69; 95% CI, 1.86-3.90).

Of note, the safety profile for durvalumab plus FLOT was consistent with the previously known profiles of the respective therapies. However, specifically, grade 3/4 adverse effects were observed in 71.6% vs 71.2% in patients from the durvalumab and placebo arms, respectively. Delayed surgery was reported in 10.1% and 10.8% of patients in the respective arms, with delayed initiation of adjuvant treatment observed in 2.3% and 4.6%.

References

1. Imfinzi granted priority review and breakthrough therapy designation in the US for patients with resectable early-stage gastric and gastroesophageal junction cancers. News release. AstraZeneca. July 28, 2025. Accessed July 28, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/imfinzi-granted-priority-review-and-breakthrough-therapy-designation-us-patients-with-resectable-early-stage-gastric-gastroesophageal-junction-cancers.html
2. Janjigian Y, Al-Batran S-E, Wainberg Z, et al. Event-free survival (EFS) in MATTERHORN: a randomized, phase 3 study of durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel chemotherapy (FLOT) in resectable gastric/gastroesophageal junction cancer (GC/GEJC). J Clin Oncol. 2025;43(suppl 17):LBA5. doi:10.1200/JCO.2025.43.17_suppl.LBA5
3. Assessing durvalumab and FLOT chemotherapy in resectable gastric and gastroesophageal junction cancer. ClinicalTrials.gov. Updated April 3, 2025. Accessed July 28, 2025. https://clinicaltrials.gov/study/NCT04592913
4. Janjigian YY, Al-Batran SE, Wainberg ZA, et al. Perioperative durvalumab in gastric and gastroesophageal junction cancer. N Engl J Med. 2025;393(3):217-230. doi:10.1056/NEJMoa2503701