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

Официальное название

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

Обзор

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).

Подробное описание

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.

Вмешательства

• Препарат Finotonlimab
  Finotonlimab
• Препарат Cetuximab
  Cetuximab
• Препарат Docetaxel
  Docetaxel
• Процедура Salvage Surgery
  Surgical resection after neoadjuvant therapy.
• Лучевая терапия Adjuvant Radiotherapy
  Adjuvant radiotherapy: after surgery, the team will assess whether the patient has indications for radiotherapy to determine whether to administer it.
• Препарат Platinum-based Chemotherapy
  Adjuvant chemotherapy determined by team assessment of chemotherapy indications after surgery.

Первичные конечные точки

• Major Pathological Response Rate (MPR) [Срок оценки: At time of surgery, approximately 12 weeks after enrollment]

Вторичные конечные точки (9)

• Objective Response Rate (ORR) [Срок оценки: After 3 cycles of neoadjuvant therapy, approximately 9 weeks]
• Pathological Complete Response Rate (pCR) [Срок оценки: At time of surgery]
• Median Overall Survival (mOS) [Срок оценки: Up to 60 months from enrollment]
• Median Progression-Free Survival (mPFS) [Срок оценки: Up to 60 months from enrollment]
• Duration of Response (DoR) [Срок оценки: Up to 60 months]
• 6-Month Progression-Free Survival Rate [Срок оценки: 6 months after end of treatment]
• 12-Month Progression-Free Survival Rate [Срок оценки: 12 months after end of treatment]
• Incidence of Adverse Events (AEs) [Срок оценки: Through study completion, up to 90 days after last dose]
• Incidence of Serious Adverse Events (SAEs) [Срок оценки: Through study completion, up to 90 days after last dose]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 9 центров

• The First People's Hospital of Foshan — Foshan
• Affiliated Cancer Hospital and Institute of Guangzhou Medical University — Гуанчжоу
• Guangzhou First People's Hospital — Гуанчжоу
• Sun Yat-sen University Cancer Center — Гуанчжоу
• The Third Affiliated Hospital of Sun Yat-sen University — Гуанчжоу
• Zhujiang Hospital of Southern Medical University — Гуанчжоу
• Cancer Hospital of Shantou University Medical College — Shantou
• Shenzhen Second People's Hospital — Шэньчжэнь
• … и ещё 1 центр

Публикации

• 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 hea PMID 38942993
• 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 PMID 34667025
• 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 PMID 38833968
• 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 metas PMID 31679945
• 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. E PMID 27718784

Идентификаторы

NCT: NCT07618624 · 2025-FXY-430

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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