Becotatug Vedotin Combined With Pucotenlimab as Neoadjuvant Therapy for Resectable Recurrent Head and Neck Squamous Cell Carcinoma After Progression on Immunotherapy: A Prospective Phase II Study (GATEWAY)
9 de maio de 2026 atualizado por: Chen Chunyan, Sun Yat-sen University
Neoadjuvant Becotatug Vedotin (Anti-EGFR ADC) Combined With Pucotenlimab (Anti-PD-1) in Patients With Resectable Recurrent Head and Neck Squamous Cell Carcinoma Who Progressed on Prior PD-1/PD-L1 Inhibitor and Platinum-Based Therapy: A Prospective, Single-Arm, Multi-Center, Phase II Clinical Trial
This is a prospective, single-arm, multi-center, Phase II clinical trial evaluating the efficacy and safety of neoadjuvant becotatug vedotin (an anti-EGFR antibody-drug conjugate) combined with pucotenlimab (HX008, an anti-PD-1 monoclonal antibody) in patients with resectable recurrent head and neck squamous cell carcinoma (rHNSCC) who have progressed on prior PD-1/PD-L1 inhibitor and platinum-based therapy.
A total of 42 EGFR-positive patients will be enrolled using Simon's two-stage design across 11 centers in China (Stage 1: 25 patients; Stage 2: 17 additional patients with 5% dropout). Enrolled patients will receive 3 cycles of neoadjuvant becotatug vedotin (2.3 mg/kg, IV, Q3W) plus pucotenlimab (3 mg/kg, IV, Q3W), followed by salvage surgery (3-4 weeks later), adjuvant radiotherapy +/- chemotherapy per NCCN/CSCO guidelines, and pucotenlimab maintenance therapy (3 mg/kg, Q3W) for up to 12 cycles or until disease progression or unacceptable toxicity.
The primary endpoint is major pathological response (MPR) rate. The null hypothesis MPR rate is 14% (historical data) and the target MPR rate is 30% (alpha=0.05, power=0.8, one-sided). Secondary endpoints include objective response rate (ORR), pathological complete response (pCR), survival outcomes, quality of life, and safety.
Visão geral do estudo
Status
Ainda não está recrutando
Intervenção / Tratamento
Descrição detalhada
Recurrent head and neck squamous cell carcinoma (rHNSCC) 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, effective treatment options are extremely limited.
Becotatug vedotin is a novel anti-EGFR antibody-drug conjugate (ADC) that has demonstrated significant anti-tumor activity in HNSCC, with an ORR of 40% in Phase Ia/Ib and 43% in the post-immunotherapy Phase II study. Pucotenlimab (HX008) is a PD-1 inhibitor with an extended half-life (T1/2 = 21.76 days). Phase I/II data showed the combination achieved ORR of 60% in HNSCC with manageable toxicity.
This study investigates neoadjuvant becotatug vedotin plus pucotenlimab in resectable rHNSCC after immunotherapy progression.
TREATMENT REGIMEN:
- Neoadjuvant: Becotatug vedotin 2.3 mg/kg IV + Pucotenlimab 3 mg/kg 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: Pucotenlimab 3 mg/kg IV Q3W for 12 cycles or until progression/toxicity
Simon's two-stage design: Stage 1 (25 patients, >=3 MPR required) to Stage 2 (17 additional, total 42). H0 MPR=14%, H1 MPR=30% (alpha=0.05, power=0.8).
Tipo de estudo
Intervencional
Inscrição (Estimado)
42
Estágio
- Fase 2
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Contato de estudo
- Nome: Xuekui Liu, MD, PhD
- Número de telefone: +86 13113348640
- E-mail: liuxk@sysucc.org.cn
Estude backup de contato
- Nome: Chunyan Chen, MD, PhD
- Número de telefone: +86 (020) 87342926
Locais de estudo
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Guangdong
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Foshan, Guangdong, China
- The First People's Hospital of Foshan
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Guangzhou, Guangdong, China
- Sun Yat-sen University Cancer Center
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Guangzhou, Guangdong, China
- Guangdong Provincial People's Hospital
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Guangzhou, Guangdong, China
- Guangzhou First People's Hospital
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Guangzhou, Guangdong, China
- ZhuJiang Hospital of Southern Medical University
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Guangzhou, Guangdong, China
- The third affiliated hospital of Sun Yat-Sen University
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Guangzhou, Guangdong, China
- Cancer Hospital of Guangzhou Medical University
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Qingyuan, Guangdong, China
- Qingyuan People's Hospital
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Shantou, Guangdong, China
- Cancer Hospital of Shantou University Medical College
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Shenzhen, Guangdong, China
- Shenzhen Second People's Hospital
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Zhanjiang, Guangdong, China
- Affiliated Hospital of Guangdong Medical University
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Jiangxi
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Ganzhou, Jiangxi, China
- Ganzhou Cancer Hospital
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-
Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Não
Descrição
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
- Disease progression after prior treatment including both PD-1/PD-L1 inhibitor and platinum-based therapy (combined or sequential)
- EGFR protein expression positive by immunohistochemistry (IHC), with no EGFR-targeted therapy within 6 months prior to enrollment
- Willing to provide archived tumor tissue or undergo fresh tumor biopsy for EGFR 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
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: N / D
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: Neoadjuvant Becotatug Vedotin + Pucotenlimab
|
Becotatug vedotin as one of the drugs used in neoadjuvant therapy.
Pucotenlimab as one of the drugs used in neoadjuvant therapy.
|
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Major Pathological Response Rate (MPR)
Prazo: At time of surgery, approximately 12 weeks after enrollment
|
Proportion of patients with less than or equal to 10% viable tumor cells in the surgically resected specimen after neoadjuvant therapy, assessed by central pathology review.
|
At time of surgery, approximately 12 weeks after enrollment
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Objective Response Rate (ORR)
Prazo: After 3 cycles of neoadjuvant therapy, approximately 9 weeks
|
Proportion of patients achieving complete response (CR) or partial response (PR) per RECIST v1.1.
|
After 3 cycles of neoadjuvant therapy, approximately 9 weeks
|
|
Pathological Complete Response Rate (pCR)
Prazo: At time of surgery
|
Proportion of patients with no residual viable tumor cells in the surgically resected specimen.
|
At time of surgery
|
|
Median Overall Survival (mOS)
Prazo: Up to 60 months from enrollment
|
Time from enrollment to death from any cause.
|
Up to 60 months from enrollment
|
|
Median Progression-Free Survival (mPFS)
Prazo: Up to 60 months from enrollment
|
Time from enrollment to disease progression per RECIST v1.1 or death from any cause.
|
Up to 60 months from enrollment
|
|
Duration of Response (DoR)
Prazo: Up to 60 months
|
Time from first documented CR or PR to disease progression or death.
|
Up to 60 months
|
|
6-Month Progression-Free Survival Rate
Prazo: 6 months after end of treatment
|
Proportion of patients alive without disease progression at 6 months after completion of study treatment.
|
6 months after end of treatment
|
|
12-Month Progression-Free Survival Rate
Prazo: 12 months after end of treatment
|
Proportion of patients alive without disease progression at 12 months after completion of study treatment.
|
12 months after end of treatment
|
|
Incidence of Adverse Events (AEs)
Prazo: Through study completion, up to 90 days after last dose
|
Safety assessed per NCI CTCAE v5.0.
Incidence and severity of all AEs, treatment-emergent AEs, and immune-related AEs.
|
Through study completion, up to 90 days after last dose
|
|
Incidence of Serious Adverse Events (SAEs)
Prazo: Through study completion, up to 90 days after last dose
|
Incidence of serious adverse events assessed per CTCAE v5.0.
|
Through study completion, up to 90 days after last dose
|
|
Quality of Life - DASS-21
Prazo: Baseline, during treatment, and follow-up through 12 months
|
Depression, Anxiety, and Stress Scale (21-item version).
|
Baseline, during treatment, and follow-up through 12 months
|
|
Quality of Life - PTGI
Prazo: Baseline and follow-up through 12 months
|
Post-Traumatic Growth Inventory.
|
Baseline and follow-up through 12 months
|
|
Quality of Life - EORTC QLQ-C30
Prazo: Baseline, during treatment, and follow-up through 12 months
|
EORTC Quality of Life Questionnaire Core 30.
|
Baseline, during treatment, and follow-up through 12 months
|
|
Stigma Scale
Prazo: Baseline and follow-up through 12 months
|
Chronic disease stigma assessment.
|
Baseline and follow-up through 12 months
|
Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Investigadores
- Cadeira de estudo: Xuekui Liu, MD, PhD, Sun Yat-sen University Cancer Center
- Cadeira de estudo: Chunyan Chen, MD, PhD, Sun Yat-sen University Cancer Center
Publicações e links úteis
A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.
Publicações Gerais
- 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. Epub 2016 Oct 8.
- 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 metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019 Nov 23;394(10212):1915-1928. doi: 10.1016/S0140-6736(19)32591-7. Epub 2019 Nov 1.
- Xu RH, et al. A first-in-human phase Ia/Ib trial of becotatug vedotin in patients with advanced solid tumors. ESMO Congress 2023.
- Xu RH, et al. Becotatug vedotin combined with pucotenlimab in patients with advanced solid tumors: A phase I/II study. 2024.
- Haddad R, et al. Neoadjuvant pembrolizumab in locally advanced head and neck squamous cell carcinoma (KEYNOTE-689). ESMO Congress 2025.
Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo (Estimado)
1 de maio de 2026
Conclusão Primária (Estimado)
1 de novembro de 2027
Conclusão do estudo (Estimado)
1 de maio de 2029
Datas de inscrição no estudo
Enviado pela primeira vez
9 de maio de 2026
Enviado pela primeira vez que atendeu aos critérios de CQ
9 de maio de 2026
Primeira postagem (Real)
15 de maio de 2026
Atualizações de registro de estudo
Última Atualização Postada (Real)
15 de maio de 2026
Última atualização enviada que atendeu aos critérios de controle de qualidade
9 de maio de 2026
Última verificação
1 de maio de 2026
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- 2025-FXY-495
Informações sobre medicamentos e dispositivos, documentos de estudo
Estuda um medicamento regulamentado pela FDA dos EUA
Não
Estuda um produto de dispositivo regulamentado pela FDA dos EUA
Não
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