BRIDGE Study: Neoadjuvant Finotonlimab, Cetuximab, and Docetaxel in Resectable Recurrent HNSCC After Immunotherapy Progression

Summary

This is a multicenter, single-arm, phase II clinical study evaluating the efficacy and safety of neoadjuvant finotonlimab (anti-PD-1), cetuximab (anti-EGFR), and docetaxel in patients with resectable recurrent head and neck squamous cell carcinoma (HNSCC) who have progressed after prior PD-1(L1) inhibitor plus platinum-based therapy. A total of 42 patients (PD-L1 CPS at least 1) will be enrolled using Simon's two-stage design across 9 centers in China (Stage 1: 25 patients; Stage 2: 17 additional patients with 5% dropout). Enrolled patients will receive 3 cycles of neoadjuvant finotonlimab (200 mg, IV, Q3W), cetuximab (500 mg/m2, IV, Q3W), and docetaxel (75 mg/m2, IV, Q3W), followed by salvage surgery (3-4 weeks later), adjuvant radiotherapy +/- chemotherapy per NCCN/CSCO guidelines, and maintenance finotonlimab 200 mg + cetuximab 500 mg/m2 Q3W for up to 12 cycles or until disease progression or unacceptable toxicity. The primary endpoint is major pathological response (MPR) rate. Historical MPR is 14% with dual immunotherapy neoadjuvant therapy; target MPR is 30% (alpha=0.05, power=0.8, one-sided). Secondary endpoints include ORR, pCR, mOS, mPFS, DoR, 6-month and 12-month PFS rate, and safety (AEs/SAEs per CTCAE v5.0).

Timeline

Start

2026-04-20

Primary completion

2027-12-31

Completion

2029-12-31

Publications

• Background Shi Y, Guo W, Wang W, Wu Y, Fang M, Huang X, Han P, Zhang Q, Dong P, Zhou X, Peng H, Hu C, Chen X, Zhang S, Chang Z, Li X, Ding Y, Qu S, Jing S, Zhang S, Gui L, Sun Y, Wang L, Liu Y, Wu H, Li G, Fu Z, Shi J, Jiang H, Bai Y, Cui J, Zheng Y, Cui W, Jia X, Zhai L, Cai Q, Xiong D, Wu Y, Cao J, Wu R, Hu G, Peng L, Xie L, Gai W, Wang Y, Su Y. Finotonlimab with chemotherapy in recurrent or metastatic head and neck cancer: a randomized phase 3 trial. Nat Med. 2024 Sep;30(9):2568-2575. doi: 10.1038/s41591-024-03110-7. Epub 2024 Jun 28.
• Background Hanna GJ, O'Neill A, Shin KY, Wong K, Jo VY, Quinn CT, Cutler JM, Flynn M, Lizotte PH, Annino DJ Jr, Goguen LA, Kass JI, Rettig EM, Sethi RKV, Lorch JH, Schoenfeld JD, Margalit DN, Tishler RB, Everett PC, Desai AM, Cavanaugh ME, Paweletz CP, Egloff AM, Uppaluri R, Haddad RI. Neoadjuvant and Adjuvant Nivolumab and Lirilumab in Patients with Recurrent, Resectable Squamous Cell Carcinoma of the Head and Neck. Clin Cancer Res. 2022 Feb 1;28(3):468-478. doi: 10.1158/1078-0432.CCR-21-2635. Epub 2021 Oct 19.
• Background Koyama T, Kiyota N, Boku S, Imamura Y, Shibata N, Satake H, Tanaka K, Hayashi H, Onoe T, Asada Y, Yamazaki T, Nose T, Ohata S, Nagatani Y, Kimbara S, Funakoshi Y, Teshima M, Shinomiya H, Minami H. A phase II trial of paclitaxel plus biweekly cetuximab for patients with recurrent or metastatic head and neck cancer previously treated with both platinum-based chemotherapy and anti-PD-1 antibody. ESMO Open. 2024 Jun;9(6):103476. doi: 10.1016/j.esmoop.2024.103476. Epub 2024 Jun 3.
• Background Burtness B, Harrington KJ, Greil R, Soulieres D, Tahara M, de Castro G Jr, Psyrri A, Baste N, Neupane P, Bratland A, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Wan Ishak WZ, Hong RL, Gonzalez Mendoza R, Roy A, Zhang Y, Gumuscu B, Cheng JD, Jin F, Rischin D; KEYNOTE-048 Investigators. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019 Nov 23;394(10212):1915-1928. doi: 10.1016/S0140-6736(19)32591-7. Epub 2019 Nov 1.
• Background Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C, Worden F, Saba NF, Iglesias Docampo LC, Haddad R, Rordorf T, Kiyota N, Tahara M, Monga M, Lynch M, Geese WJ, Kopit J, Shaw JW, Gillison ML. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med. 2016 Nov 10;375(19):1856-1867. doi: 10.1056/NEJMoa1602252. Epub 2016 Oct 8.

Drugs

Indications