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)
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.
연구 개요
상세 설명
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).
연구 유형
등록 (추정된)
단계
- 2 단계
연락처 및 위치
연구 연락처
- 이름: Xuekui Liu, MD, PhD
- 전화번호: +86 13113348640
- 이메일: liuxk@sysucc.org.cn
연구 연락처 백업
- 이름: Chunyan Chen, MD, PhD
- 전화번호: +86 (020) 87342926
연구 장소
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Guangdong
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Foshan, Guangdong, 중국
- The First People's Hospital of Foshan
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Guangzhou, Guangdong, 중국
- Sun Yat-sen University Cancer Center
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Guangzhou, Guangdong, 중국
- Guangdong Provincial People's Hospital
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Guangzhou, Guangdong, 중국
- Guangzhou First People's Hospital
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Guangzhou, Guangdong, 중국
- ZhuJiang Hospital of Southern Medical University
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Guangzhou, Guangdong, 중국
- The third affiliated hospital of Sun Yat-Sen University
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Guangzhou, Guangdong, 중국
- Cancer Hospital of Guangzhou Medical University
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Qingyuan, Guangdong, 중국
- Qingyuan People's Hospital
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Shantou, Guangdong, 중국
- Cancer Hospital of Shantou University Medical College
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Shenzhen, Guangdong, 중국
- Shenzhen Second People's Hospital
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Zhanjiang, Guangdong, 중국
- Affiliated Hospital of Guangdong Medical University
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Jiangxi
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Ganzhou, Jiangxi, 중국
- Ganzhou Cancer Hospital
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참여기준
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
설명
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
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
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실험적: 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.
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Major Pathological Response Rate (MPR)
기간: At time of surgery, approximately 12 weeks after enrollment
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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.
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At time of surgery, approximately 12 weeks after enrollment
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Objective Response Rate (ORR)
기간: After 3 cycles of neoadjuvant therapy, approximately 9 weeks
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Proportion of patients achieving complete response (CR) or partial response (PR) per RECIST v1.1.
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After 3 cycles of neoadjuvant therapy, approximately 9 weeks
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Pathological Complete Response Rate (pCR)
기간: At time of surgery
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Proportion of patients with no residual viable tumor cells in the surgically resected specimen.
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At time of surgery
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Median Overall Survival (mOS)
기간: Up to 60 months from enrollment
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Time from enrollment to death from any cause.
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Up to 60 months from enrollment
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Median Progression-Free Survival (mPFS)
기간: Up to 60 months from enrollment
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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
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Duration of Response (DoR)
기간: Up to 60 months
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Time from first documented CR or PR to disease progression or death.
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Up to 60 months
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6-Month Progression-Free Survival Rate
기간: 6 months after end of treatment
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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
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12-Month Progression-Free Survival Rate
기간: 12 months after end of treatment
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Proportion of patients alive without disease progression at 12 months after completion of study treatment.
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12 months after end of treatment
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Incidence of Adverse Events (AEs)
기간: Through study completion, up to 90 days after last dose
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Safety assessed per NCI CTCAE v5.0.
Incidence and severity of all AEs, treatment-emergent AEs, and immune-related AEs.
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Through study completion, up to 90 days after last dose
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Incidence of Serious Adverse Events (SAEs)
기간: Through study completion, up to 90 days after last dose
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Incidence of serious adverse events assessed per CTCAE v5.0.
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Through study completion, up to 90 days after last dose
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Quality of Life - DASS-21
기간: 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
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Quality of Life - PTGI
기간: Baseline and follow-up through 12 months
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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
기간: Baseline, during treatment, and follow-up through 12 months
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EORTC Quality of Life Questionnaire Core 30.
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Baseline, during treatment, and follow-up through 12 months
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Stigma Scale
기간: Baseline and follow-up through 12 months
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Chronic disease stigma assessment.
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Baseline and follow-up through 12 months
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공동 작업자 및 조사자
수사관
- 연구 의자: Xuekui Liu, MD, PhD, Sun Yat-sen University Cancer Center
- 연구 의자: Chunyan Chen, MD, PhD, Sun Yat-sen University Cancer Center
간행물 및 유용한 링크
일반 간행물
- 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.
연구 기록 날짜
연구 주요 날짜
연구 시작 (추정된)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
키워드
추가 관련 MeSH 약관
기타 연구 ID 번호
- 2025-FXY-495
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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