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Head and Neck Squamous Cell CarcinomaPhase 2GATEWAYNCT07589049

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

A Phase 2 study testing Becotatug Vedotin and Pucotenlimab in people with Head and Neck Squamous Cell Carcinoma, run by Sun Yat-sen University at 12 sites in China.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Head and Neck Squamous Cell Carcinoma
What is being tested?
Becotatug Vedotin and Pucotenlimab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
12 sitesChina
Study dates
May 2026to May 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 12Show fewer
  • 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

Who cannot join

  • 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
Show all 13Show fewer
  • 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

Trial locations and contacts

12 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Xuekui Liu, MD, PhD contact

+86 13113348640

liuxk@sysucc.org.cn

Chunyan Chen, MD, PhD contact

+86 (020) 87342926

12 sites in 1 country

China12 sites

  • The First People's Hospital of Foshan

    Foshan, Guangdong

  • Ganzhou Cancer Hospital

    Ganzhou, Jiangxi

  • Cancer Hospital of Guangzhou Medical University

    Guangzhou, Guangdong

  • Guangdong Provincial People's Hospital

    Guangzhou, Guangdong

  • Guangzhou First People's Hospital

    Guangzhou, Guangdong

  • Sun Yat-sen University Cancer Center

    Guangzhou, Guangdong

  • The Third Affiliated Hospital of Sun Yat-sen University

    Guangzhou, Guangdong

  • Zhujiang Hospital of Southern Medical University

    Guangzhou, Guangdong

  • Qingyuan People's Hospital

    Qingyuan, Guangdong

  • Cancer Hospital of Shantou University Medical College

    Shantou, Guangdong

  • Shenzhen Second People's Hospital

    Shenzhen, Guangdong

  • Affiliated Hospital of Guangdong Medical University

    Zhanjiang, Guangdong

Other trials in China

About this study

Official title: 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.

Read the 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).

Being tested
Becotatug Vedotin, Pucotenlimab
Keywords
Becotatug Vedotin, EGFR ADC, Pucotenlimab, HX008, Neoadjuvant Therapy, Recurrent Head and Neck Cancer, GATEWAY, Immunotherapy Progression, Salvage Surgery, Major Pathological Response
Medical subject headings
Squamous Cell Carcinoma of Head and Neck, Head and Neck Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Becotatug VedotinDrug

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

  • PucotenlimabDrug

    Pucotenlimab as one of the drugs used in neoadjuvant therapy.

Study groups in NCT07589049
Study groupRoleWhat they receive
Neoadjuvant Becotatug Vedotin + PucotenlimabExperimentalNot described
Receives: Drug: Becotatug Vedotin; Drug: Pucotenlimab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: At time of surgery, approximately 12 weeks after enrollment

Secondary outcomes (13)

  1. Objective Response Rate (ORR)

    Proportion of patients achieving complete response (CR) or partial response (PR) per RECIST v1.1.

    Measured: After 3 cycles of neoadjuvant therapy, approximately 9 weeks

  2. Pathological Complete Response Rate (pCR)

    Proportion of patients with no residual viable tumor cells in the surgically resected specimen.

    Measured: At time of surgery

  3. Median Overall Survival (mOS)

    Time from enrollment to death from any cause.

    Measured: Up to 60 months from enrollment

  4. Median Progression-Free Survival (mPFS)

    Time from enrollment to disease progression per RECIST v1.1 or death from any cause.

    Measured: Up to 60 months from enrollment

  5. Duration of Response (DoR)

    Time from first documented CR or PR to disease progression or death.

    Measured: Up to 60 months

  6. 6-Month Progression-Free Survival Rate

    Proportion of patients alive without disease progression at 6 months after completion of study treatment.

    Measured: 6 months after end of treatment

  7. 12-Month Progression-Free Survival Rate

    Proportion of patients alive without disease progression at 12 months after completion of study treatment.

    Measured: 12 months after end of treatment

  8. Incidence of Adverse Events (AEs)

    Safety assessed per NCI CTCAE v5.0. Incidence and severity of all AEs, treatment-emergent AEs, and immune-related AEs.

    Measured: Through study completion, up to 90 days after last dose

  9. Incidence of Serious Adverse Events (SAEs)

    Incidence of serious adverse events assessed per CTCAE v5.0.

    Measured: Through study completion, up to 90 days after last dose

  10. Quality of Life - DASS-21

    Depression, Anxiety, and Stress Scale (21-item version).

    Measured: Baseline, during treatment, and follow-up through 12 months

  11. Quality of Life - PTGI

    Post-Traumatic Growth Inventory.

    Measured: Baseline and follow-up through 12 months

  12. Quality of Life - EORTC QLQ-C30

    EORTC Quality of Life Questionnaire Core 30.

    Measured: Baseline, during treatment, and follow-up through 12 months

  13. Stigma Scale

    Chronic disease stigma assessment.

    Measured: Baseline and follow-up through 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 May 2026
  2. Study startMay 2026 (estimated)
  3. Primary completionNov 2027 (estimated)
  4. Study completionMay 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Single Group Assignment
Masking
None (open label)
Enrolment
42 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07589049
Sponsor's protocol ID
2025-FXY-495
Acronym
GATEWAY
Status last verified
May 2026
First submitted
9 May 2026
Last updated
15 May 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 31679945

  • 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.

    PubMed 27718784

  • 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.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Becotatug Vedotin and Pucotenlimab in people with Head and Neck Squamous Cell Carcinoma, run by Sun Yat-sen University at 12 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 15 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Xuekui Liu, MD, PhD (+86 13113348640, liuxk@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Major Pathological Response Rate (MPR) (time frame: At time of surgery, approximately 12 weeks after enrollment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07589049, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2026.

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