Tislelizumab Plus Chemotherapy as First-line Treatment for Advanced Esophageal Squamous Cell Carcinoma and Gastric/Gastroesophageal Junction Adenocarcinoma.

Purpose: This phase 2 study (NCT03469557) assessed safety/tolerability and antitumor activity of first line tislelizumab, a monoclonal antibody against PD-1, plus chemotherapy in patients with locally advanced/metastatic esophageal squamous cell carcinoma (ESCC) or gastric cancer/gastroesophageal junction (G/GEJ) adenocarcinoma. Experimental Design: Patients with ESCC received tislelizumab (200mg IV every 3 weeks [Q3W]) plus cisplatin (80mg/m² IV Q3W for ≤6 cycles) and fluorouracil (800mg/m²/d, Days 1-5 IV Q3W for ≤6 cycles); patients with G/GEJ adenocarcinoma received tislelizumab (200mg IV Q3W) plus oxaliplatin (130mg/m² IV Q3W for up to six cycles) and oral capecitabine (1000mg/m² twice daily, Days 1-14 Q3W). The safety/tolerability profile of combination therapy was the primary endpoint; secondary endpoints included objective response rate (ORR), duration of response (DoR), disease control rate (DCR), and progression-free survival per RECIST v1.1. Exploratory endpoints included overall survival and potential predictive biomarkers. Results:As of March 31, 2019, 30 patients (n=15 per cohort) were enrolled. Most common adverse events considered related to tislelizumab and/or chemotherapy were anemia (n=18), decreased appetite (n=17), nausea (n=16), and asthenia (n=15). One patient experienced fatal hepatic dysfunction, confounded by progressive disease and underlying hepatitis, attributed to treatment by the investigator. Confirmed ORRs and DCRs were 46.7% and 80%, respectively, for both ESCC and G/GEJ adenocarcinoma. In ESCC, median DoR was 12.8 months (95% CI: 3.5, 12.8); DoR was not yet mature for the G/GEJ cohort. Conclusions: Tislelizumab plus chemotherapy demonstrated durable responses with manageable tolerability in patients with advanced ESCC or G/GEJ adenocarcinoma.