Finotonlimab Combined With Cetuximab and Docetaxel as Neoadjuvant Therapy for Resectable Recurrent Head and Neck Squamous Cell Carcinoma After Immunotherapy Progression: A Multicenter, Single-Arm, Phase II Clinical Study
试验速览
- 阶段
- 2 期
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 42
- 试验地点
- 9
研究概览
简要总结
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).
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究者
Chen Chunyan
Principal Investigator
Sun Yat-sen University