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

Recurrent head and neck squamous cell carcinoma (HNSCC) remains a significant clinical challenge, with recurrence rates of 40-60% after curative treatment. Salvage surgery is the standard of care, yet approximately 50% of patients experience re-recurrence within 2 years. For patients who have progressed on prior PD-1 inhibitor and platinum-based therapy, no standard neoadjuvant regimen exists.

Finotonlimab (SCT-I10A) is a recombinant humanized anti-PD-1 monoclonal antibody approved by NMPA for first-line R/M HNSCC in combination with platinum-based chemotherapy. Phase III data showed mOS 14.1 months and ORR 39.9% (Nature Medicine, 2024). Cetuximab is an anti-EGFR monoclonal antibody approved for R/M HNSCC. Cetuximab plus taxane regimens showed ORR of 54.9-69.6% as second-line therapy after immunotherapy failure. Retrospective data suggest EGFR inhibition may enhance anti-tumor immune response and improve efficacy of PD-1 rechallenge (ORR 46.4%). Docetaxel is a standard taxane chemotherapeutic agent.

This study investigates a novel neoadjuvant triplet regimen combining finotonlimab (immunotherapy), cetuximab (EGFR targeting), and docetaxel (chemotherapy) in resectable recurrent HNSCC after immunotherapy progression.

TREATMENT REGIMEN:

• Neoadjuvant: Finotonlimab 200 mg IV + Cetuximab 500 mg/m2 IV + Docetaxel 75 mg/m2 IV, Q3W, 3 cycles
• Surgery: Salvage surgery 3-4 weeks after neoadjuvant completion
• Adjuvant: IMRT (60-66 Gy/30f) +/- platinum-based chemotherapy per NCCN/CSCO
• Maintenance: Finotonlimab 200 mg IV + Cetuximab 500 mg/m2 IV Q3W for 12 cycles or until progression/toxicity

Simon's two-stage design: Stage 1 (25 patients; at least 3 MPR required to proceed) to Stage 2 (17 additional, total 42). H0 MPR=14%, H1 MPR=30% (alpha=0.05, power=0.8). If 9 or fewer total responses, the trial is considered negative.

Inclusion criteria

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Age 18-75 years at time of consent
• Histologically or cytologically confirmed recurrent head and neck squamous cell carcinoma with PD-L1 CPS at least 1
• Disease progression after prior treatment including both PD-1(L1) inhibitor and platinum-based therapy (combined or sequential)
• No EGFR-targeted therapy within 6 months prior to enrollment
• Willing to provide archived tumor tissue or undergo fresh tumor biopsy for PD-L1 testing
• 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
• Resectable disease with no distant metastasis, as assessed by a multidisciplinary team
• 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
• Signed informed consent prior to any study-specific procedures
• Life expectancy greater than 3 months
• Effective contraception during study and for 6 months after last dose

Exclusion criteria

• History of other malignancies (except cured basal cell carcinoma or cervical carcinoma in situ)
• Comorbidities requiring long-term immunosuppressive therapy or corticosteroids at immunosuppressive doses
• Immunodeficiency or history of organ transplantation (including interstitial pneumonia, hepatitis, nephritis, hyperthyroidism, hypothyroidism)
• 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
• High-dose systemic corticosteroids within 4 weeks prior to enrollment
• Pregnant or lactating women; fertile patients not using effective contraception
• Laboratory values not meeting inclusion criteria within 7 days
• Significantly impaired cardiac, hepatic, pulmonary, renal, or bone marrow function
• Severe uncontrolled comorbidities or active infections
• Concurrent participation in other clinical trials
• Refusal or inability to sign informed consent
• Other contraindications to study treatment as determined by the investigator
• Psychiatric disorders or mental illness resulting in lack of legal capacity