Neoadjuvant IBI110 and sintilimab in combination with chemotherapy in resectable locally advanced head and neck squamous cell carcinoma.

Abstract

e18092 Background: Lymphocyte-activation gene 3 (LAG-3) has emerged as a novel target for immunotherapy. Herein, we reported a phase Ib trial to investigate the efficacy and safety of neoadjuvant chemotherapy (NAC) with Sintilimab, with or without an anti-Lag-3 antibody (IBI110), in resectable locally advanced head and neck squamous cell carcinoma (LA HNSCC). Methods: Eligible patients(pts) with pathologic confirmed, resectable LA HNSCC (AJCC 8 th III-IVB) were enrolled in two cohorts: cohort A (Sintilimab and NAC) and cohort B (Sintilimab combined with IBI110 and NAC). In cohort A, eligible pts were given Sintilimab 200mg d1, paclitaxel 175mg/m2 d2, and cisplatin 25mg/m2 d2-4 intravenously, one course every 3 weeks(Q3w), for a total of 2 courses. Radical surgery was performed 3-5 weeks after the 2nd NCT. Adjuvant radiotherapy (chemoradiation) was performed according to postoperative pathological factors. Cohort A is expected to enroll 15 pts. In cohort B, pts were given IBI110 200mg d1, Sintilimab 200mg d1, combined with paclitaxel and cisplatin, once Q3W, for a total of 2 cycles. Surgery and adjuvant therapy was the same as cohort A. Considering that there was no dose recommendation for dual immunotherapy combined with TP regimen, a dose escalation phase was set up in cohort B: fixed doses of IBI110 and Sintilimab were given, and the doses of paclitaxel and cisplatin were escalated to explore R2PD. Pts were divided into three dose levels: paclitaxel 135mg/m2 d2, cisplatin 20mg/m2 d2-4 (n=1); paclitaxel 150mg/m2 d2, cisplatin 20mg/m2 d2-4 (n=1); paclitaxel 175mg/m2 d2, cisplatin 25mg/m2 d2-4 (n=3). An accelerated escalation schedule was used. After exploring R2PD, pts continued to be enrolled in the fixed dose expansion phase until 12 cases enrolled. The primary endpoints were major pathological response rate (MPR), and treatment-related adverse events (TRAEs). Results: As of January 20, 2025, cohort A has enrolled 5 pts, and cohort B has completed enrollment with a total of 12 pts. In cohort B, clinical stage III (33.3%), IV (58.3%), p16+ (33.3%), and 83.3% of pts had a history of smoking. In the dose escalation phase, 5 pts were enrolled, and no DLT was observed. The recommended dose was paclitaxel 175mg/m2 d2, cisplatin 25mg/m2 d2-4; a total of 7 pts were enrolled in the expansion phase. All pts completed 2 cycles of neoadjuvant treatment, and the ORR was 58.3%. Among the 12 pts, 8 received surgery, 3 received radiotherapy, and 1 refused follow-up treatment. Among the 8 surgical pts, the MPR rate was 75% and the pCR rate was 50%. During neoadjuvant therapy, TRAE occurred in all pts, including grade ≥3 TRAEs in 6 (50%) pts. Immune-related adverse events (irAEs) occurred in 6 (50%) pts, including grade ≥3 irAEs in 2 (16.7%) pts. Conclusions: Sintilimab and IBI110 combined with TP regimen NAC achieved an encouraging efficacy in pts with resectable LA HNSCC, with a manageable safety profile. Clinical trial information: NCT06494943 .