Pembrolizumab plus nab-paclitaxel and platinum as first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC): A prospective, single-arm, open-label, phase 2 study.

6023 Background: Based on KN-048, pembrolizumab combined with PF regimen has become the first-line standard treatment for R/M HNSCC. KN-B10 confirmed pembrolizumab combined with carboplatin and paclitaxel has a promising effect with manageable safety. This study aims to supplement the efficacy and safety data of pembrolizumab combined with nab-paclitaxel and platinum in the Chinese population. Methods: Untreated R/M HNSCC patients were treated with pembrolizumab 200mg, nab-paclitaxel 260mg/m 2 , plus cisplatin 75 mg/m 2 or carboplatin AUC 5 (only if patients have cisplatin contraindications) on day 1 every 21 days for up to six cycles, followed by pembrolizumab maintenance therapy until progression or intolerable toxicity or completion of 35 cycles. Efficacy was evaluated according to RECIST 1.1, and survival analysis was performed using the Kaplan-Meier method. Adverse events were assessed using the CTCAE 5.0. The primary endpoint was ORR. Secondary endpoints include safety, DCR, OS, and PFS. High-resolution sequencing based on probe capture was performed on eligible patients. Results: Between Sep 15, 2020, and Nov 8, 2023, 67 R/M HNSCC patients were enrolled. Baseline characteristics are shown in the table. The median follow-up time was 12.7 months at the data cut-off date of January 8th, 2023, the ORR was 62.7%, and the DCR was 88.1%. The median PFS and OS were 11.6 months and 18.7 months, respectively. The median DOR was 14.7 months. The most common TRAEs of grade ≥3 were leukopenia (22.4%) and neutropenia (28.4%). Grade≥3 immune-related AEs were pneumonitis (1.5%), hepatitis (1.5%), and enteritis (1.5%). Of the 35 patients with sequencing results, the most common alterations were the TP53 mutation (86%), CDKN2A mutation (22%), FGF19 (26%), FGF4 (20%), FGF3 (20%), and CCND1 (20%) amplification. FGF19, FGF4, FGF3, and CCND1 amplification were associated with poor ORR, and CDKN2A mutation was associated with poor OS. Conclusions: Pembrolizumab combined with nab-paclitaxel and platinum shows encouraging antitumor activity accompanied by a manageable safety profile in untreated R/M HNSCC patients in China. CDKN2A mutation was a potential independent prognostic factors for this patient population. Clinical trial information: NCT04857164 . Table: see text