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 mayo de 2026 actualizado 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.
Descripción general del estudio
Estado
Aún no reclutando
Intervención / Tratamiento
Descripción detallada
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 estudio
Intervencionista
Inscripción (Estimado)
42
Fase
- Fase 2
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Estudio Contacto
- Nombre: Xuekui Liu, MD, PhD
- Número de teléfono: +86 13113348640
- Correo electrónico: liuxk@sysucc.org.cn
Copia de seguridad de contactos de estudio
- Nombre: Chunyan Chen, MD, PhD
- Número de teléfono: +86 (020) 87342926
Ubicaciones de estudio
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Guangdong
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Foshan, Guangdong, Porcelana
- The First People's Hospital of Foshan
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Guangzhou, Guangdong, Porcelana
- Sun Yat-sen University Cancer Center
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Guangzhou, Guangdong, Porcelana
- Guangdong Provincial People's Hospital
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Guangzhou, Guangdong, Porcelana
- Guangzhou First People's Hospital
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Guangzhou, Guangdong, Porcelana
- ZhuJiang Hospital of Southern Medical University
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Guangzhou, Guangdong, Porcelana
- The third affiliated hospital of Sun Yat-Sen University
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Guangzhou, Guangdong, Porcelana
- Cancer Hospital of Guangzhou Medical University
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Qingyuan, Guangdong, Porcelana
- Qingyuan People's Hospital
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Shantou, Guangdong, Porcelana
- Cancer Hospital of Shantou University Medical College
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Shenzhen, Guangdong, Porcelana
- Shenzhen Second People's Hospital
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Zhanjiang, Guangdong, Porcelana
- Affiliated Hospital of Guangdong Medical University
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Jiangxi
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Ganzhou, Jiangxi, Porcelana
- Ganzhou Cancer Hospital
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
No
Descripción
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
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: Neoadjuvant Becotatug Vedotin + Pucotenlimab
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Becotatug vedotin as one of the drugs used in neoadjuvant therapy.
Pucotenlimab as one of the drugs used in neoadjuvant therapy.
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Major Pathological Response Rate (MPR)
Periodo de tiempo: 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 resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Objective Response Rate (ORR)
Periodo de tiempo: 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)
Periodo de tiempo: At time of surgery
|
Proportion of patients with no residual viable tumor cells in the surgically resected specimen.
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At time of surgery
|
|
Median Overall Survival (mOS)
Periodo de tiempo: 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)
Periodo de tiempo: Up to 60 months from enrollment
|
Time from enrollment to disease progression per RECIST v1.1 or death from any cause.
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Up to 60 months from enrollment
|
|
Duration of Response (DoR)
Periodo de tiempo: 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
Periodo de tiempo: 6 months after end of treatment
|
Proportion of patients alive without disease progression at 6 months after completion of study treatment.
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6 months after end of treatment
|
|
12-Month Progression-Free Survival Rate
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: Baseline, during treatment, and follow-up through 12 months
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Depression, Anxiety, and Stress Scale (21-item version).
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Baseline, during treatment, and follow-up through 12 months
|
|
Quality of Life - PTGI
Periodo de tiempo: Baseline and follow-up through 12 months
|
Post-Traumatic Growth Inventory.
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Baseline and follow-up through 12 months
|
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Quality of Life - EORTC QLQ-C30
Periodo de tiempo: Baseline, during treatment, and follow-up through 12 months
|
EORTC Quality of Life Questionnaire Core 30.
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Baseline, during treatment, and follow-up through 12 months
|
|
Stigma Scale
Periodo de tiempo: Baseline and follow-up through 12 months
|
Chronic disease stigma assessment.
|
Baseline and follow-up through 12 months
|
Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Investigadores
- Silla de estudio: Xuekui Liu, MD, PhD, Sun Yat-sen University Cancer Center
- Silla de estudio: Chunyan Chen, MD, PhD, Sun Yat-sen University Cancer Center
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
- 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.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Estimado)
1 de mayo de 2026
Finalización primaria (Estimado)
1 de noviembre de 2027
Finalización del estudio (Estimado)
1 de mayo de 2029
Fechas de registro del estudio
Enviado por primera vez
9 de mayo de 2026
Primero enviado que cumplió con los criterios de control de calidad
9 de mayo de 2026
Publicado por primera vez (Actual)
15 de mayo de 2026
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
15 de mayo de 2026
Última actualización enviada que cumplió con los criterios de control de calidad
9 de mayo de 2026
Última verificación
1 de mayo de 2026
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 2025-FXY-495
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
No
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .