Envafolimab plus chemotherapy as neoadjuvant therapy for resectable esophageal squamous cell carcinoma (ESCC): A prospective, single-arm, phase II study.

Abstract

e14633 Background: Currently, chemotherapy plus PD-1 inhibitor immunotherapy has become a promising option in the neoadjuvant setting of resectable ESCC, nevertheless, the PD-ligand 1 (PD-L1) blockade-based combination has rarely been investigated to date. Envafolimab is the first and only globally approved subcutaneous (SC) PD-L1 inhibitor, which has shown satisfactory efficacy and safety profile in tumors. This Simon’s two-stage, phase II study explored the safety and feasibility of SC administration of envafolimab as an alternative to intravenous (IV) administration of PD-1/PD-L1 inhibitors in the neoadjuvant therapy of resectable ESCC. Here, we reported the results of the stage 1. Methods: In this Simon’s two-stage, phase II study, patients initially treated with locally advanced and resectable (stage II-IVA) ESCC were enrolled and received envafolimab (300mg, SC, day 1), albumin-bound paclitaxel (130mg/m2, IV, days 1 and 8), and carboplatin (AUC = 5, day 1) every 3 weeks for 3 cycles. The primary endpoints were safety and pathological complete response (pCR). A Simon’s two-stage design was utilized with following assumptions. Target accrual was 13 patients in the first stage (If 3 or more patients had pCR in stage 1, study could continue in stage 2), total 34 patients were enrolled in the stage 2. Secondary endpoints were major pathological response (MPR). Safety was assessed by adverse events (AEs) and postoperative complications. Results: Between October 2022 and April 2023, 13 (81.3%) of 16 enrolled patients completed neoadjuvant therapy and underwent surgery. All 13 (100%) surgical patients underwent successful R0 resection; of whom, 8 (61.5%) achieved pCR and 9 (69.2%) achieved MPR, respectively. Downstaging occurred in 10 (76.9%) of 13 patients. pCR and MPR were identified to be associated with tumor downstaging but not with PD-L1 expression. CPS levels in MPR and pCR group were significantly higher than that in Non- MPR and Non-pCR group. Grade 3-4 treatment-related AEs (TRAEs) and immune-related AEs (IrAEs) occurred in 12.5% and 37.5% of 16 patients, respectively. 10 (76.9%) of 13 patients reported postoperative complications. No treatment-related surgical delay or death occurred. Conclusions: Envafolimab plus chemotherapy as neoadjuvant therapy demonstrated promising antitumor activity for resectable ESCC with high rates of pCR, MPR and R0 resection, as well as acceptable tolerability. Based on the encouraging efficacy of our regimen in the first stage, we will continue the enrollment of patients in stage 2. Keywords: Esophageal squamous cell carcinoma; Envafolimab; Neoadjuvant therapy; Chemotherapy Clinical trial information: NCT05552651 .