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).

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:

1. Neoadjuvant: Finotonlimab 200 mg IV + Cetuximab 500 mg/m2 IV + Docetaxel 75 mg/m2 IV, Q3W, 3 cycles
2. Surgery: Salvage surgery 3-4 weeks after neoadjuvant completion
3. Adjuvant: IMRT (60-66 Gy/30f) +/- platinum-based chemotherapy per NCCN/CSCO
4. 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:

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