Phase I-II trial of perioperative chemotherapy plus atezolizumab and tiragolumab in localized esophageal and gastroesophageal junction adenocarcinoma.

418 Background: Management of esophageal and gastroesophageal junction (GEJ) adenocarcinoma focuses on perioperative strategies to increase pathological complete response rates, delay or eliminate metastases, and prolong overall survival. Atezolizumab is a humanized IgG1 monoclonal antibody that blocks PD-L1 from binding its inhibitory receptors, PD-1 and B7-1, thereby boosting tumor-specific T-cell responses and anti-tumor activity. Tiragolumab is a fully human IgG1/κ monoclonal antibody targeting TIGIT, an inhibitory receptor on activated T cells and NK cells that binds CD155. Blocking TIGIT could further enhance T-cell responses. Combining tiragolumab with atezolizumab and chemotherapy may improve outcomes in patients with localized esophageal and GEJ adenocarcinoma. Methods: We conducted a phase I/II study to evaluate the efficacy and safety of combining atezolizumab and tiragolumab with modified FOLFOX (oxaliplatin and 5-fluorouracil) in the perioperative treatment of localized esophageal and GEJ type I or II adenocarcinoma. Eligible patients were treatment naïve with T1N1 or T2-3 (any N) GEJ adeno. Treatment involved FOLFOX on days 1 and 15, followed by atezolizumab (840 mg IV) and tiragolumab (420 mg IV) on the same days of each 28-day cycle, for a total of six doses. Surgery was performed afterward, followed by adjuvant atezolizumab (1200 mg IV) plus tiragolumab (600 mg IV) on day 1 administered every 21 days for sixteen cycles. Results: Twenty-three patients (median age 67) were enrolled (stage IIb: n=6; stage III: n=13; stage IVa: n=4). Twenty patients were evaluated for efficacy. Thus far, 16 patients had undergone surgery. Pathological complete response (pCR, T0N0) has been observed in 18.8% (3/16; 95% CI: 4.1–45.7%), with 1 additional patient showing near-complete response (