Background PD-1 inhibitors and EGFR inhibitors are effective and may provide potential synergy in R/M HNSCC. An open-label, multicenter phase Ib/II study of toripalimab (a humanized IgG4K monoclonal antibody specific for PD-1) with cetuximab was conducted in platinum-refractory or PD-L1 positive previously untreated R/M-HNSCC (NCT04856631). Here we report the results of Cohort A (platinum-refractory).
Methods Eligible patients with R/M HNSCC progressed upon 1st-line platinum-containing treatment or developed R/M disease within 6 months of platinum-containing neo-adjuvant/adjuvant or chemo-radiation therapy who had no prior immunotherapy or EGFR inhibitors therapy were enrolled. Toripalimab was administered at 240mg intravenously (IV) Q3W and cetuximab was given as a loading dose of 400mg/m2 IV followed by 250mg/m2 QW. The primary endpoint was objective response rate (ORR) by an independent review committee (IRC) per RECIST v1.1. Secondary endpoints included ORR, disease control rates (DCR), duration of response (DOR), progression-free survival (PFS) by the investigators and IRC, overall survival (OS), and safety.
Results By the data cutoff date of Apr. 14, 2023, a total of 45 patients including 35 (77.8%) males were enrolled in Cohort A, with the median follow-up duration of 10.0 months. The median age of the patients was 59 (range 32–74) years. Eighteen (40.0%) patients had distant metastases and 31 (68.9%) were PD-L1 CPS ≥1. As assessed by the IRC, the confirmed ORR was 60% (95% CI 44.3%, 74.3%) with 1 CR and 26 PR, and the median DOR was 17.9 (95% CI 7.8, NA) months, the median PFS was 9.9 (95% CI 4.2, NA) months, 12 months PFS rate was 40.7%. Similar results were seen per investigators’ assessment. The median OS was 15.4 (95% CI 8.5, 17.7) months, 12 months OS rate was 54.4%. Patients with positive PD-L1 expression (CPS≥1) may benefit more than negative patients (ORR: 64.5% vs 40%, median PFS: 10.4 m vs 4.0 m, median OS: 15.4 m vs 11.7 m). Forty-two (93.3%) patients experienced treatment-related adverse events (TRAEs). Eleven (24.4%) patients experienced immune-related adverse events (irAEs). Ten (22.2%) patients occurred Grade≥3 TRAEs and no Grade≥3 irAEs occurred. No fatal AEs related to the study treatment was reported.
Conclusions Toripalimab combined with cetuximab were well tolerated and showed promising clinical efficacy in patients with R/M HNSCC.
Trial Registration NCT04856631
Ethics Approval The study obtained ethics approval from Shanghai East Hospital Drug clinical Trial Ethics Committee [&x4E34;&x5BA1;&x7B2C; (072) &x53F7;], and participants gave informed consent before taking part.
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