Efficacy and safety of neoadjuvant zimberelimab and cetuximab plus nab-paclitaxel and cisplatin (NeoZCPC) for resectable locally advanced hypopharyngeal/laryngeal squamous cell carcinoma: An open-label, single-arm phase II clinical trial.

Abstract

e18095 Background: Locally advanced hypopharyngeal/laryngeal squamous cell carcinoma (LA-HLSCC) patients necessitate novel therapeutic approaches to improve their laryngeal preservation rate and quality of life. Cetuximab has been proven to be an alternative to 5-FU when combined with docetaxel and cisplatin but provides no superior objective response rate. Based on the synergistic effect of PD-1 on anti-tumor activity, this phase II trial aimed to investigate the efficacy and safety of neoadjuvant zimberelimab (a PD-1 antibody) and cetuximab plus nab-paclitaxel and cisplatin (NeoZCPC) for resectable LA-HLSCC. Methods: In this open-label, single-arm clinical trial, patients with untreated, resectable LA-HLSCC (T2N2-3M0, T3-4N0-3M0; stage III-IVB, AJCC 8th Ed) were enrolled to receive NeoZCPC, in which zimberelimab (240 mg), cisplatin (60 mg/m 2 ), and nab-paclitaxel (260 mg/m 2 ) were administered on day 1 of each 21-day cycle for three cycles, and cetuximab was given 400 mg/m 2 on day 1 and 250 mg/m 2 per week for 8 additional weeks, followed by surgery or definitive radiotherapy. The primary endpoint was objective response rate (ORR) per RECIST 1.1. Secondary endpoints included pathological complete response (pCR), major pathological response (MPR), laryngeal preservation rate (LPR), progression-free survival (PFS), and overall survival (OS). Results: Between September 2023 and December 2024, 26 patients were enrolled (median [range] age was 60 [41-76] years; 26 male). The primary lesions were located at the hypopharynx (10/26, 38.5%) and larynx (16/26, 61.5%). After the completion of NeoZCPC, the ORR was 96.2% [25/26], including 50% [13/26] CR and 46.2% [12/26] PR. There were 11 (42.3%) patients receiving subsequent definitive radiotherapy and 15 (57.7%) patients receiving surgery, among which the pCR rate was 33.3% [5/15] and the MPR rate was 40% [6/15]. Grade 1-2 treatment-related adverse events (TRAEs) occurred in 5 (19.2%) patients. Grade 4 TRAEs were reported in only 3 (11.5%) patients, including allergic reaction (7.7%), pneumonitis (3.8%), heart failure (3.8%), and myocardial infarction (3.8%). LPR, PFS, and OS data were still not yet mature as of the cutoff date (January 1, 2025). Conclusions: NeoZCPC achieved promising ORR, pCR, and MPR rate with acceptable toxicities in LA-HLSCC patients. Follow-up is still underway to obtain long-term survival data. Clinical trial information: NCT06107114 .