Retlirafusp alfa-a bifunctional anti-PD-L1/TGF-βRII agent plus nab-paclitaxel and carboplatin in pre-treated recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC): A prospective, single-arm, phase II clinical trial.

Abstract

6029 Background: Treatment for pre-treated patients (pts) with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is an important unmet clinical need. Dual blockade of PD-L1 and TGF-β could reshape the tumor microenvironment. The aim of this study is to evaluate the efficacy and safety of retlirafusp alfa (SHR-1701, a bifunctional anti-PD-L1/TGF-βRII agent) plus nab-paclitaxel and carboplatin in platinum-refractory R/M HNSCC pts. Methods: Patients with R/M HNSCC who received ≥1 line of prior systemic anti-tumor therapy were included. Pts received retlirafusp alfa 30mg/kg, once every 3 weeks, combined with nab-paclitaxel (125mg/m 2 ) and carboplatin (AUC=1.5), on day 1 and day 8 of a 21-day cycle for up to six cycles, followed by retlirafusp alfa maintenance therapy. The primary endpoint was objective response rate (ORR). Secondary endpoints comprised progression free survival (PFS), overall survival (OS), disease control rate (DCR) and safety. Results: From September 5, 2023 to September 25, 2024, 12 eligible pts were enrolled. The median age was 60 (range: 35-72). Among these 12 patients, 11 (91.7%) had received prior immune checkpoint inhibitors (ICIs) and 8 (66.7%) had undergone at least two previous lines of treatment. The median follow-up was 5.45 (95%CI 3.93-6.97) months, and data cutoff was December 31, 2024. All the 12 pts had at least one post-baseline assessment, and 4 pts achieved partial response with a confirmed ORR of 33.33% (95%CI 13.81%-60.93%). Disease control was observed in 8 patients resulting in a DCR of 66.67% (95%CI 39.07%-86.19%). The median PFS was 4.21 (95%CI 0.59-7.83) months. The median OS was immature. Treatment-related adverse events (TRAEs) occurred in 11 (91.67%) pts, mainly grade 1-2. The most common TRAEs (≥30%) were anaemia (8/12, 66.67%), white blood cell count decreased (5/12, 41.67%), hypoalbuminaemia (5/12, 41.67%), haemoptysis (5/12, 41.67%) and epistaxis (4/12, 33.33%). Grade 3-4 TRAEs were observed in 4 (33.33%) pts, with more than 1 patient experiencing white blood cell count decreased (3/12, 25%), neutrophil count decreased (2/12, 16.67%) and anaemia (2/12, 16.67%). Conclusions: Even as most pts have progressed on ICIs before enrollment, retlirafusp alfa plus nab-paclitaxel and carboplatin demonstrated promising anti-tumor efficacy and manageable toxicities in pre-treated R/M HNSCC. Long-term efficacy needs to be confirmed by further follow-up. Clinical trial information: ChiCTR2300070675 .