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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 maggio 2026 aggiornato da: 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.

Panoramica dello studio

Stato

Non ancora reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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:

  1. Neoadjuvant: Becotatug vedotin 2.3 mg/kg IV + Pucotenlimab 3 mg/kg 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: 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 di studio

Interventistico

Iscrizione (Stimato)

42

Fase

  • Fase 2

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Backup dei contatti dello studio

  • Nome: Chunyan Chen, MD, PhD
  • Numero di telefono: +86 (020) 87342926

Luoghi di studio

  • Cina
    • Guangdong
      • Foshan, Guangdong, Cina
        • The First People's Hospital of Foshan
      • Guangzhou, Guangdong, Cina
        • Sun yat-sen University Cancer Center
      • Guangzhou, Guangdong, Cina
        • Guangdong Provincial People's Hospital
      • Guangzhou, Guangdong, Cina
        • Guangzhou First People's Hospital
      • Guangzhou, Guangdong, Cina
        • Zhujiang Hospital of Southern Medical University
      • Guangzhou, Guangdong, Cina
        • The Third Affiliated Hospital Of Sun Yat-Sen University
      • Guangzhou, Guangdong, Cina
        • Cancer Hospital of Guangzhou Medical University
      • Qingyuan, Guangdong, Cina
        • Qingyuan People's Hospital
      • Shantou, Guangdong, Cina
        • Cancer Hospital of Shantou University Medical College
      • Shenzhen, Guangdong, Cina
        • Shenzhen Second People's Hospital
      • Zhanjiang, Guangdong, Cina
        • Affiliated Hospital of Guangdong Medical University
    • Jiangxi
      • Ganzhou, Jiangxi, Cina
        • Ganzhou Cancer Hospital

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

  • Adulto
  • Adulto più anziano

Accetta volontari sani

No

Descrizione

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
  4. Disease progression after prior treatment including both PD-1/PD-L1 inhibitor and platinum-based therapy (combined or sequential)
  5. EGFR protein expression positive by immunohistochemistry (IHC), with no EGFR-targeted therapy within 6 months prior to enrollment
  6. Willing to provide archived tumor tissue or undergo fresh tumor biopsy for EGFR 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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: N / A
  • Modello interventistico: Assegnazione di gruppo singolo
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Neoadjuvant Becotatug Vedotin + Pucotenlimab
Droga: Becotatug Vedotin
Becotatug vedotin as one of the drugs used in neoadjuvant therapy.
Droga: Pucotenlimab
Pucotenlimab as one of the drugs used in neoadjuvant therapy.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Major Pathological Response Rate (MPR)
Lasso di tempo: 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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Objective Response Rate (ORR)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: Baseline and follow-up through 12 months
Post-Traumatic Growth Inventory.
Baseline and follow-up through 12 months
Quality of Life - EORTC QLQ-C30
Lasso di tempo: 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
Lasso di tempo: Baseline and follow-up through 12 months
Chronic disease stigma assessment.
Baseline and follow-up through 12 months

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Sun Yat-sen University

Investigatori

  • Cattedra di studio: Xuekui Liu, MD, PhD, Sun yat-sen University Cancer Center
  • Cattedra di studio: Chunyan Chen, MD, PhD, Sun yat-sen University Cancer Center

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Stimato)

1 maggio 2026

Completamento primario (Stimato)

1 novembre 2027

Completamento dello studio (Stimato)

1 maggio 2029

Date di iscrizione allo studio

Primo inviato

9 maggio 2026

Primo inviato che soddisfa i criteri di controllo qualità

9 maggio 2026

Primo Inserito (Effettivo)

15 maggio 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

15 maggio 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

9 maggio 2026

Ultimo verificato

1 maggio 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • 2025-FXY-495

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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