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

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).

Sex

All

Minimum age

18 Years

Maximum age

75 Years

INCLUSION CRITERIA:

1. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
2. Age 18-75 years at time of consent
3. Histologically or cytologically confirmed recurrent head and neck squamous cell carcinoma with PD-L1 CPS at least 1
4. Disease progression after prior treatment including both PD-1(L1) inhibitor and platinum-based therapy (combined or sequential)
5. No EGFR-targeted therapy within 6 months prior to enrollment
6. Willing to provide archived tumor tissue or undergo fresh tumor biopsy for PD-L1 testing
7. At least one measurable extracranial lesion per RECIST v1.1; previously treated lesions must demonstrate clear progression 3 or more months after last local treatment
8. Resectable disease with no distant metastasis, as assessed by a multidisciplinary team
9. Adequate organ function within 7 days prior to enrollment: ANC at least 2.0 x 10\^9/L, platelet count at least 100 x 10\^9/L; total bilirubin less than 1.5 x ULN, ALT/AST less than 2.5 x ULN; serum creatinine less than 1.5 x ULN
10. Signed informed consent prior to any study-specific procedures
11. Life expectancy greater than 3 months
12. Effective contraception during study and for 6 months after last dose

EXCLUSION CRITERIA:

1. History of other malignancies (except cured basal cell carcinoma or cervical carcinoma in situ)
2. Comorbidities requiring long-term immunosuppressive therapy or corticosteroids at immunosuppressive doses
3. Immunodeficiency or history of organ transplantation (including interstitial pneumonia, hepatitis, nephritis, hyperthyroidism, hypothyroidism)
4. HIV/AIDS; untreated active hepatitis B (HBV-DNA at least 500 IU/mL); hepatitis C (HCV-RNA above detection limit); or HBV/HCV co-infection
5. High-dose systemic corticosteroids within 4 weeks prior to enrollment
6. Pregnant or lactating women; fertile patients not using effective contraception
7. Laboratory values not meeting inclusion criteria within 7 days
8. Significantly impaired cardiac, hepatic, pulmonary, renal, or bone marrow function
9. Severe uncontrolled comorbidities or active infections
10. Concurrent participation in other clinical trials
11. Refusal or inability to sign informed consent
12. Other contraindications to study treatment as determined by the investigator
13. Psychiatric disorders or mental illness resulting in lack of legal capacity

• BACKGROUNDShi 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. PMID 38942993
• BACKGROUNDHanna 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. PMID 34667025
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