Induction adebrelimab combined with chemotherapy followed by response-adaptive concurrent chemoradiotherapy guided by PET-CT in locally advanced unresectable esophageal squamous cell carcinoma: A prospective, single-arm, phase II study.

Abstract

TPS2692 Background: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced unresectable esophageal cancer. Currently, data on PD-L1 inhibitors combined with chemoradiotherapy in this setting still remain limited. Furthermore, the efficacy of induction immunotherapy prior to CCRT, and the utility of PET-CT assessment to guide subsequent CCRT regimens, have not been explored. This study aims to evaluate the efficacy and safety of induction adebrelimab (an anti-PD-L1 antibody) combined with chemotherapy, followed by a PET-CT guided adaptive chemotherapy regimen during CCRT for locally advanced unresectable esophageal squamous cell carcinoma (ESCC). Methods: This single-arm, open-label, exploratory study will recruit 36 patients with locally advanced unresectable ESCC (clinical stage T1N+M0 or T2-4bNxM0) who have not received prior antitumor treatment. Patients will undergo 2 cycles of induction therapy with adebrelimab (1200 mg, d1, iv, q3w) plus the TP regimen (nab-paclitaxel 180 mg/m² or paclitaxel 135 mg/m², d1, iv; carboplatin AUC=5, d1, iv, q3w). Following induction, response will be assessed via PET-CT. Responders (defined as SUV reduction ≥35% or partial response ) will continue with the TP regimen (nab-paclitaxel 60 mg/m² or paclitaxel 50 mg/m², d1, iv; carboplatin AUC=2, d1, iv, qw for 5 cycles) during concurrent radiation (50.4–60 Gy/28–33f). Non-responders will switch to the FP regimen (fluorouracil 750–1000 mg/m², civ 96h; cisplatin 75 mg/m², d1, iv, q4w for 2 cycles) during concurrent radiation. All patients will proceed to maintenance therapy with adebrelimab following CCRT until disease progression or unacceptable toxicity. The primary endpoint is the 1-year progression-free survival (PFS) rate. Secondary endpoints include the clinical complete response (cCR) rate, objective response rate (ORR), disease control rate (DCR), duration of response (DoR), PFS, overall survival (OS), and safety profile. Clinical trial information: NCT07112833 .