Neoadjuvant atezolizumab plus docetaxel/oxaliplatin/capecitabine in non-metastatic gastric and gastroesophageal junction adenocarcinoma: The PANDA trial.

4059 Background: Immune checkpoint blockade improves clinical outcomes for patients with gastric and gastro-esophageal junction (GEJ) cancers, but its efficacy and impact on the tumor microenvironment in non-metastatic, resectable disease remains largely unknown. Peri-operative FLOT, the current standard-of-care, leads to pathologic complete responses (pCR) and major pathologic responses (MPR) in 16% and 37% of patients, respectively. An important open question is whether PDL-1 blockade monotherapy can prime the tumor microenvironment in a favorable manner, prior to combination with chemotherapy. Methods: We report results from the phase 2 PANDA trial (NCT03448835) of neoadjuvant atezolizumab (anti-PDL-1) plus docetaxel, oxaliplatin, and capecitabine (DOC) in patients with resectable gastric or GEJ adenocarcinoma. Patients received a single cycle of atezolizumab monotherapy, followed by 4 cycles of atezolizumab+DOC. Tumor tissue was collected at baseline, after atezolizumab monotherapy, the first atezolizumab+DOC, and at resection. The primary endpoints were safety and feasibility in 20 patients, and secondary endpoints included MPR (<10% viable tumor rest) and disease-free survival. Results: Twenty patients, of which 18 with mismatch repair (MMR) proficient and two with MMR-deficient tumors, were evaluable for safety and efficacy analyses. MPR was observed in 14/20 patients (70%; 95% CI 46–88%), including 9 pCR (45%; 95% CI 23-68%). Among patients with intestinal type adenocarcinoma, 12/15 (80%; 95% CI 52-96%) had an MPR, with 9/15 (60%; 95% CI 32-84%) pCR. Treatment was well tolerated, with two patients (10%) experiencing a grade 3 immune adverse event. At a median follow-up of 29 months (IQR 16-34), 15 patients (75%) were alive and disease-free. None of the patients with an MPR recurred. All patients underwent resections without treatment-related delays and no unexpected surgical complications were documented. Translational analyses, including baseline PDL-1 CPS score and whole exome sequencing (WES), plus CD8 T-cell infiltration and RNA sequencing at 4 timepoints will be presented at the meeting. Conclusions: Our data show that the addition of atezolizumab to neoadjuvant chemotherapy leads to promising pathologic responses in gastric/GEJ adenocarcinoma, which appears to be higher than in historical controls, with no recurrences in responders. These data should be validated in a large randomized controlled trial. Clinical trial information: NCT03448835.