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 (<1% viable tumor). R0 resection rate was 87.5%. There were no grade 4 treatment-related adverse events, deaths or treatment discontinuations. At a median follow-up of 21.1 months, four patients had died. Estimated 1- and 2-year survival rates were 94.1% and 74.0%, respectively. Conclusions: Results indicate that atezolizumab and tiragolumab in combination with oxaliplatin and 5-fluorouracil has an acceptable safety profile providing high rate of tumor regression. This trial supports further research checkpoint inhibition in patients with localized esophageal and GEJ adenocarcinomas in the perioperative setting. Clinical trial information: NCT03784326 .