Perioperative chemotherapy with LP002, an anti-PD-L1 antibody, in patients with resectable gastric and gastroesophageal junction cancer: A prospective, open-label, phase Ib trial.

Abstract

4041 Background: Immune checkpoint inhibitors were effective, either alone or in combination with chemotherapy, in pts with metastatic gastric or gastroesophageal junction (GEJ) cancers, but their role for resectable disease remained unknown. We report the safety and pathological response of gastric/GEJ cancer pts receiving LP002, an anti-PD-L1 antibody, plus chemotherapy as perioperative treatment in a phase Ib trial. Methods: We enrolled pts with previously untreated, PD-L1 positive, resectable (cT2-4a, any N, M0) gastric/GEJ cancer. Eligible pts received three preoperative and six postoperative 2-week cycles of intravenous LP002 900mg on day 1, intravenous cisplatin 50 mg/m2 on day 1, and 2000 mg/m2 5-fluorouracil as 48-h infusion starting on day 1. The standard surgery was scheduled 4-6 weeks after completion of 3 cycles of preoperative treatment. The primary endpoint was safety. Secondary endpoints included proportion of pts with R0 resection and pathological complete response (pCR), disease-free survival, and overall survival. With pre- and post-treatment samples, we also characterized genomic changes in tumor tissue with next generation sequencing (NGS), and alterations in the tumor immune microenvironment (TIME) using multiplex immunofluorescence staining. Results: From September 2020 to July 2021, 30 pts were enrolled into this study. The median age was 64.5 years (range, 50-74). Most primary tumors were in the GEJ (N=28, 93.3%). 29 pts (96.7%) had adenocarcinoma, and 1 had small cell neuroendocrine tumor. The median follow-up duration was 7.9 months (range: 5.1-10.6) as of data cut-off (November 1, 2021). All pts completed the planned preoperative treatment, and 27 pts (90.0%) proceeded to surgery. Reasons for surgery not being performed were metastatic disease in 1 patient, and patient request in 2 cases. 24 pts had R0 resection, while 3 underwent R1 resection. 1 patient achieved pCR (TRG 1 per the Mandard’s tumor regression grading system) and 5 pts (18.5%) reached TRG 2-3. Treatment-related adverse events (TRAEs) were observed in 27 pts during perioperative treatment. Most of the TRAEs were of grade 1 to 2. The most common grade 3 toxicities were nausea (23.3%), neutrophil count decreased (16.7%) and anorexia (6.7%). 11 pts had immune-related adverse events, mostly grade 1 hyperthyroidism (45.5%). There were no grade 4-5 TRAEs. NGS analysis revealed that the mutation frequencies of the 733 genes in the sequencing panel decreased after preoperative treatment in pts with TRG 2-3. The analysis of TIME is undergoing. Conclusions: LP002 plus cisplatin and 5-fluorouracil was safe in pts with resectable gastric or GEJ cancer, and could be a new perioperative treatment option for PD-L1 positive disease. Pts are followed-up for survival outcomes. Clinical trial information: NCT04755543.