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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. maj 2026 opdateret af: 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.

Studieoversigt

Status

Ikke rekrutterer endnu

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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).

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

42

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

Undersøgelse Kontakt Backup

  • Navn: Chunyan Chen, MD, PhD
  • Telefonnummer: +86 (020) 87342926

Studiesteder

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

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

  • Voksen
  • Ældre voksen

Tager imod sunde frivillige

Ingen

Beskrivelse

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

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Neoadjuvant Becotatug Vedotin + Pucotenlimab
Medicin: Becotatug Vedotin
Becotatug vedotin as one of the drugs used in neoadjuvant therapy.
Medicin: Pucotenlimab
Pucotenlimab as one of the drugs used in neoadjuvant therapy.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Major Pathological Response Rate (MPR)
Tidsramme: 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

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Objective Response Rate (ORR)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: Baseline and follow-up through 12 months
Post-Traumatic Growth Inventory.
Baseline and follow-up through 12 months
Quality of Life - EORTC QLQ-C30
Tidsramme: 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
Tidsramme: Baseline and follow-up through 12 months
Chronic disease stigma assessment.
Baseline and follow-up through 12 months

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Sun Yat-sen University

Efterforskere

  • Studiestol: Xuekui Liu, MD, PhD, Sun Yat-sen University Cancer Center
  • Studiestol: Chunyan Chen, MD, PhD, Sun Yat-sen University Cancer Center

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Anslået)

1. maj 2026

Primær færdiggørelse (Anslået)

1. november 2027

Studieafslutning (Anslået)

1. maj 2029

Datoer for studieregistrering

Først indsendt

9. maj 2026

Først indsendt, der opfyldte QC-kriterier

9. maj 2026

Først opslået (Faktiske)

15. maj 2026

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

15. maj 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

9. maj 2026

Sidst verificeret

1. maj 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • 2025-FXY-495

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