Abstract CT009: Phase II trial of perioperative pembrolizumab plus capecitabine and oxaliplatin followed by adjuvant pembrolizumab for resectable gastric and gastroesophageal junction (GC/GEJ) adenocarcinoma

Abstract Background: Perioperative therapy for locally advanced (LA) GC/GEJ adenocarcinoma is standard of care. Although immune checkpoint blockade (ICB) following chemoradiotherapy and resection significantly improves disease free survival (DFS) for esophageal cancer, the effectiveness of ICB together with chemotherapy in LA GC/GEJ cancer is unknown. Methods: This is a multicenter, single-arm, phase II clinical trial of pembrolizumab 200 mg every 3 weeks with capecitabine 625 mg/m2 twice daily and oxaliplatin 130 mg/m2 every 3 weeks (CAPOX) in patients with resectable GC/GEJ adenocarcinoma. Subjects with ECOG PS of 0-1 received CAPOX with pembrolizumab for 3 cycles prior to and 3 cycles following surgery with an additional cycle of pembrolizumab just prior to surgery and 12 months of maintenance pembrolizumab following adjuvant chemoimmunotherapy. The primary endpoint was pathologic complete response (pCR) rate. The study had 80% power to detect an increase in pCR rate from 3% to 15% with a one-sided alpha of 0.05. Secondary endpoints included overall response rate, DFS, and overall survival (OS). This study was registered with ClinicalTrials.gov (NCT02918162). Results: Between 02/10/2017 and 06/17/2021, 36 patients were enrolled with 34 (21 gastric and 13 GEJ) evaluable for efficacy. The median age was 65 years and 17 (50%) patients had an ECOG PS of 1. In total, 29 (85%) patients underwent resection. Seven patients achieved a pCR (20.6% of evaluable patients and 24.1% of those who underwent resection). An additional 6 (17.6%) patients achieved a near CR and 8 (23.5%) demonstrated a significant treatment effect on pathologic review. One patient was deemed unfit for surgery, 2 expired prior to surgery, and 2 were found to have metastatic disease during surgery. At the time of data cut-off, the median follow-up was 19 mo. Of those who underwent resection, 4 (13.7%) experienced disease recurrence and 5 (17.2%) expired. The probability of survival at 1 and 2 years was 0.91 (0.82-1.0) and 0.80 (0.64-0.99), respectively. The median DFS and OS have not been reached. Of the 35 patients who received treatment, treatment related adverse events (AEs) of grade greater than or equal to 3 were reported in 18 (51%) patients. Grade greater than or equal to 3 immune-related AEs were reported in 10 (29%) patients. Three grade 5 AEs occurred, two possibly treatment-related (gastric hemorrhage and gastric perforation) and one unrelated to treatment (cardiac arrest). Conclusion: In LA GC/GEJ adenocarcinoma, the combination CAPOX and pembrolizumab resulted in a pCR rate of 20.6%. The combination was well tolerated and 85.3% of patients underwent surgical resection. This trial met its primary endpoint supporting further investigation of this regimen as an alternative for patients who are unlikely to tolerate triple combination chemotherapy. Correlative studies are in progress. Citation Format: Alexander Grenander Raufi, Shing Lee, Michael May, Armando Del Portillo, Naomi Sender, Sarah Sta Ana, Katarzyna Gautier, Emily Alouani, Haeseong Park, Paul Oberstein, Manish Shah, Gulam A. Manji. Phase II trial of perioperative pembrolizumab plus capecitabine and oxaliplatin followed by adjuvant pembrolizumab for resectable gastric and gastroesophageal junction (GC/GEJ) adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT009.