NCT07589049

Brief Summary

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.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
42

participants targeted

Target at P25-P50 for phase_2

Timeline
36mo left

Started May 2026

Typical duration for phase_2

Geographic Reach
1 country

12 active sites

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress2%
May 2026May 2029

Study Start

First participant enrolled

May 1, 2026

Completed
8 days until next milestone

First Submitted

Initial submission to the registry

May 9, 2026

Completed
6 days until next milestone

First Posted

Study publicly available on registry

May 15, 2026

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2027

Expected
1.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2029

Last Updated

May 15, 2026

Status Verified

May 1, 2026

Enrollment Period

1.5 years

First QC Date

May 9, 2026

Last Update Submit

May 9, 2026

Conditions

Head and Neck Squamous Cell Carcinoma

Keywords

Becotatug VedotinEGFR ADCPucotenlimabHX008Neoadjuvant TherapyRecurrent Head and Neck CancerGATEWAYImmunotherapy ProgressionSalvage SurgeryMajor Pathological Response

Outcome Measures

Primary Outcomes (1)

  • Major Pathological Response Rate (MPR)

    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 Outcomes (13)

  • Objective Response Rate (ORR)

    After 3 cycles of neoadjuvant therapy, approximately 9 weeks

  • Pathological Complete Response Rate (pCR)

    At time of surgery

  • Median Overall Survival (mOS)

    Up to 60 months from enrollment

  • Median Progression-Free Survival (mPFS)

    Up to 60 months from enrollment

  • Duration of Response (DoR)

    Up to 60 months

  • +8 more secondary outcomes

Study Arms (1)

Neoadjuvant Becotatug Vedotin + Pucotenlimab

EXPERIMENTAL
Drug: Becotatug VedotinDrug: Pucotenlimab

Interventions

Becotatug VedotinDRUG

Becotatug vedotin as one of the drugs used in neoadjuvant therapy.

Neoadjuvant Becotatug Vedotin + Pucotenlimab
PucotenlimabDRUG

Pucotenlimab as one of the drugs used in neoadjuvant therapy.

Neoadjuvant Becotatug Vedotin + Pucotenlimab

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (12)

The First People's Hospital of Foshan

Foshan, Guangdong, China

Location

Cancer Hospital of Guangzhou Medical University

Guangzhou, Guangdong, China

Location

Guangdong Provincial People's Hospital

Guangzhou, Guangdong, China

Location

Guangzhou First People's Hospital

Guangzhou, Guangdong, China

Location

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Location

The Third Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, China

Location

Zhujiang Hospital of Southern Medical University

Guangzhou, Guangdong, China

Location

Qingyuan People's Hospital

Qingyuan, Guangdong, China

Location

Cancer Hospital of Shantou University Medical College

Shantou, Guangdong, China

Location

Shenzhen Second People's Hospital

Shenzhen, Guangdong, China

Location

Affiliated Hospital of Guangdong Medical University

Zhanjiang, Guangdong, China

Location

Ganzhou Cancer Hospital

Ganzhou, Jiangxi, China

Location

Related Publications (5)

  • 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.

    PMID: 31679945BACKGROUND

  • 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.

    PMID: 27718784BACKGROUND

  • Xu RH, et al. A first-in-human phase Ia/Ib trial of becotatug vedotin in patients with advanced solid tumors. ESMO Congress 2023.

    BACKGROUND

  • Xu RH, et al. Becotatug vedotin combined with pucotenlimab in patients with advanced solid tumors: A phase I/II study. 2024.

    BACKGROUND

  • Haddad R, et al. Neoadjuvant pembrolizumab in locally advanced head and neck squamous cell carcinoma (KEYNOTE-689). ESMO Congress 2025.

    BACKGROUND

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and NeckHead and Neck Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Squamous CellCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsNeoplasms by Site

Study Officials

  • Xuekui Liu, MD, PhD

    Sun Yat-Sen University Cancer Center

    STUDY CHAIR

  • Chunyan Chen, MD, PhD

    Sun Yat-Sen University Cancer Center

    STUDY CHAIR

Central Study Contacts

Xuekui Liu, MD, PhD

CONTACT

+86 13113348640liuxk@sysucc.org.cn

Chunyan Chen, MD, PhD

CONTACT

+86 (020) 87342926

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Model Details: Single Group Assignment
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

May 9, 2026

First Posted

May 15, 2026

Study Start

May 1, 2026

Primary Completion (Estimated)

November 1, 2027

Study Completion (Estimated)

May 1, 2029

Last Updated

May 15, 2026

Record last verified: 2026-05

Locations

CN(12)