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)

May 9, 2026 updated by: 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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

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).

Study Type

Interventional

Enrollment (Estimated)

42

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Chunyan Chen, MD, PhD
  • Phone Number: +86 (020) 87342926

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Neoadjuvant Becotatug Vedotin + Pucotenlimab
Drug: Becotatug Vedotin
Becotatug vedotin as one of the drugs used in neoadjuvant therapy.
Drug: Pucotenlimab
Pucotenlimab as one of the drugs used in neoadjuvant therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Major Pathological Response Rate (MPR)
Time Frame: 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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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
Time Frame: 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
Time Frame: 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)
Time Frame: 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)
Time Frame: 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
Time Frame: 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
Time Frame: Baseline and follow-up through 12 months
Post-Traumatic Growth Inventory.
Baseline and follow-up through 12 months
Quality of Life - EORTC QLQ-C30
Time Frame: 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
Time Frame: Baseline and follow-up through 12 months
Chronic disease stigma assessment.
Baseline and follow-up through 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-sen University

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2026

Primary Completion (Estimated)

November 1, 2027

Study Completion (Estimated)

May 1, 2029

Study Registration Dates

First Submitted

May 9, 2026

First Submitted That Met QC Criteria

May 9, 2026

First Posted (Actual)

May 15, 2026

Study Record Updates

Last Update Posted (Actual)

May 15, 2026

Last Update Submitted That Met QC Criteria

May 9, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2025-FXY-495

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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