872P - Safety and efficacy of toripalimab combined with cetuximab in PD-L1 positive untreated recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC): A phase Ib/II study

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 (NCT04856631) was conducted to explore the safety and efficacy of toripalimab (anti-PD-1) combined with cetuximab in platinum-refractory (Cohort A) or previously untreated PD-L1 positive (Cohort B) R/M HNSCC patients. Here we report the preliminary results of Cohort B.

Methods

Eligible patients must have histologically confirmed R/M HNSCC, PD-L1 expression positive (combined positive score [CPS] ≥ 1), and no prior exposure to systemic therapies for R/M disease or progressed at least 6 months after systemic therapy with curative intent for local-regional disease. Patients would receive toripalimab 240 mg intravenously (IV) Q3W and cetuximab (loading dose of 400 mg/m² IV followed by 250 mg/m² QW). The primary endpoint was investigator-assessed objective response rate (ORR) per RECIST v1.1. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

Results

From June 29, 2022 to April 7, 2023, a total of 43 patients were enrolled in Cohort B. The median age was 60 (range 41-73) years, and 39 (90.7%) patients were male. 21 (48.8%) patients had a primary tumor site in oral cavity, 23 (53.5%) had local recurrence only and 18 (41.9%) were PD-L1 CPS ≥ 20. As of March 21, 2024, the median follow-up duration was 12.0 months. The confirmed ORR was 41.9 (95% CI 27.0, 57.9) % with 2 CR, 16 PR and 16 SD observed. The median DOR was 15.8 (95% CI 9.4, NE) months. The median PFS was 8.2 (95% CI 4.2, 16.8) months and 1-year PFS rate was 44.0%. The estimated median OS was 18.1 (95% CI 10.6, NE) months and 1-year OS rate was 62.2%. 40 (93.0%) patients experienced treatment-related adverse events, with 12 (27.9%) Grade ≥ 3. AE led to treatment discontinuation in 1 (2.3%) patient. 1 (2.3%) treatment-related death was reported. No novel safety signal was observed beyond the known risk profiles of toripalimab and cetuximab.

Conclusions

Toripalimab combined with cetuximab showed promising clinical efficacy and manageable safety profile in previously untreated PD-L1 positive R/M HNSCC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Shanghai Junshi Biosciences.

Funding

Shanghai Junshi Biosciences.

Disclosure

All authors have declared no conflicts of interest.