Neoadjuvant EGFR-ADC Combined With Anti-PD-1 Monoclonal Antibody in Resectable Locally Advanced Hypopharyngeal Squamous Cell Carcinoma (RESERVE-HC)

June 18, 2026 updated by: Tianjin Medical University Cancer Institute and Hospital

A Multicenter, Phase II Clinical Trial of Neoadjuvant Becotatug Vedotin Combined With Pucotenlimab in Resectable Locally Advanced Hypopharyngeal Squamous Cell Carcinoma

This clinical trial aims to evaluate the efficacy and safety of Becotatug Vedotin (EGFR-ADC) in combination with Pucotenlimab(Anti-PD-1 Monoclonal Antibody) as neoadjuvant therapy for patients with Resectable Locally Advanced Hypopharyngeal Squamous Cell Carcinoma.

The primary objective is the pathological complete response(pCR)rate following neoadjuvant therapy. The secondary objective includes the major pathological response(MPR)rate following neoadjuvant therapy, the objective response rate (ORR), Organ preservation rate, Surgery postponement rate, event-free survival (EFS), overall survival(OS), and safety.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This study is a multicenter, phase II clinical trial of neoadjuvant Becotatug Vedotin (EGFR-ADC) combined with Pucotenlimab (Anti-PD-1 monoclonal antibody) in patients with resectable locally advanced hypopharyngeal squamous cell carcinoma. Eligible participants will receive Becotatug Vedotin plus Pucotenlimab as preoperative neoadjuvant therapy, intravenous infusion every 3 weeks (Q3W) for 3 cycles.Tumor assessment will be performed after two cycles of neoadjuvant treatment. If, upon evaluation by the investigator, participants achieve a complete response (CR) based on radiographic assessment after two cycles, they may proceed directly to radical surgical resection. In the event of disease progression, severe adverse events, or intolerable toxicity during the neoadjuvant phase, the investigator may decide to discontinue neoadjuvant therapy and initiate radical therapy.

Study Type

Interventional

Enrollment (Estimated)

52

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

Study Locations

  • China
    • Tianjin Municipality
      • Tianjin, Tianjin Municipality, China, 300060
        • Tianjin Medical University Cancer Institute and Hospital, Tianjin, Tianjin 300000
        • Contact:
        • Contact:

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. Aged ≥ 18, male or female;
  2. Histopathologically confirmed Hypopharyngeal Squamous Cell Carcinoma;
  3. Surgically resectable, Clinical Stage III or IV and no distant metastasis (AJCC 8th edition);

3. Measurable primary lesions per RECIST v1.1; 5.Treatment-naive (no prior anti-tumor therapy for current disease); 6.ECOG performance status 0-1; 7.Estimated life expectancy >= 3 months; 8.Have adequate organ function as defined by laboratory parameters; 9.No contraindications to chemotherapy, targeted therapy, or immunotherapy; 10.No history of immune-related diseases; 11.No uncontrolled pneumonia or pulmonary infection; 12.Female participants of childbearing potential must agree to use effective contraception during the trial; A serum or urine pregnancy test must be negative within 72 hours prior to the start of chemotherapy; 13.The subject is volunteer to participate, and the subject must signed an informed consent form (ICF), indicating that it understands the purpose of this study and the required procedures, and is willing to participate in the study. Subjects must be willing and abide by prohibition and restrictions specified in the research program; Subjects are willing and able to follow the trial and follow-up procedures.

Exclusion Criteria:

  1. Patients with distant metastasis;
  2. Patients with uncontrolled severe medical conditions;
  3. Patients with a history of allergy or hypersensitivity to any component of monoclonal antibody therapies;
  4. Uncontrolled cardiac clinical symptoms or diseases;
  5. Occurrence of severe infection (CTCAE Grade > 2) within 4 weeks prior to the first dose of the study drug;
  6. Unexplained fever > 38.5°C during the screening period or before the first dose;
  7. Active autoimmune disease or a history of autoimmune disease;
  8. History of immunodeficiency, or a history of organ transplantation or allogeneic bone marrow transplantation;
  9. Patients with untreated chronic hepatitis B, or chronic hepatitis B virus (HBV) DNA exceeding 500 IU/mL, or patients with active hepatitis C virus (HCV) must be excluded;
  10. History of interstitial lung disease;
  11. Patients with active pulmonary tuberculosis infection identified by medical history or CT scan;

  12. Patients who have received any of the following treatments:

    A. Receipt of any investigational drug or anti-cancer therapy within 4 weeks prior to the first dose of the study drug; B. Requirement for systemic treatment with corticosteroids (daily dose > 10 mg prednisone equivalent) or other immunosuppressive medications within 2 weeks prior to the first dose of the study drug.; C. Prior vaccination with an anti-tumor vaccine or receipt of a live vaccine within 4 weeks prior to the first dose of the study drug; D. Major surgery or significant traumatic injury within 4 weeks prior to the first dose of the study drug; E. Concurrent enrollment in another clinical study;

  13. Dementia, altered mental status, or any psychiatric condition that would interfere with understanding or providing informed consent or completing questionnaires;
  14. Subjects with peripheral neuropathy ≥ Grade 2 according to CTCAE V5.0;
  15. History of allergy or hypersensitivity to any component of the study treatment;
  16. History of a primary malignancy other than head and neck squamous cell carcinoma within the previous 5 years;
  17. Requirement for concurrent treatment with other anti-tumor therapies;
  18. Patients deemed unsuitable for enrollment by the investigator;
  19. Pregnant or breastfeeding women.

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: Combination Therapy with Becotatug Vedotin and Pucotenlimab
Drug: Becotatug Vedotin and Pucotenlimab
Neoadjuvant therapy: Becotatug Vedotin is dosed based on the participant's body weight. In this study, the dosing regimen is 2.3 mg/kg, administered via intravenous infusion on Day 1 of each cycle, once every 3 weeks (Q3W), for a total of 3 treatment cycles. The infusion time for Becotatug Vedotin should be no less than 60min, and it is recommended to be controlled within 60 to 90min. Pucotenlimab is administered at a fixed dose of 200 mg per infusion, via intravenous infusion on Day 1 of each cycle, once every 3 weeks (Q3W), for a total of 3 treatment cycles, with an infusion duration of 60min (±15 min). When Becotatug Vedotin and Pucotenlimab are administered on the same day, Pucotenlimab is generally given first, followed by Becotatug Vedotin, with an interval of no less than 30min between the two infusions.
Other Names:
  • Becotatug Vedotin(MRG003)
  • Pucotenlimab(HX008)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathological Complete Response(pCR) Rate
Time Frame: At the time of surgery (approximately 3-4 weeks after the completion of neoadjuvant therapy)
The proportion of participants with no residual tumor cells in the resected primary tumor specimen after the completion of neoadjuvant therapy.
At the time of surgery (approximately 3-4 weeks after the completion of neoadjuvant therapy)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Major Pathological Response(MPR) Rate
Time Frame: At the time of surgery (approximately 3-4 weeks after the completion of neoadjuvant therapy)
The proportion of participants who achieve a major pathological response, defined as residual viable tumor cells ≤ 10% in the resected primary tumor specimen following neoadjuvant therapy.
At the time of surgery (approximately 3-4 weeks after the completion of neoadjuvant therapy)
Objective Response Rate（ORR）
Time Frame: After 2 cycles or 3 cycles of neoadjuvant therapy
The proportion of participants who achieve a complete response (CR) or partial response (PR) as assessed by RECIST version 1.1 after completion of neoadjuvant therapy.
After 2 cycles or 3 cycles of neoadjuvant therapy
Event-Free Survival (EFS)
Time Frame: From start of study treatment up to approximately 3 years
The time from the start of study treatment to the first occurrence of any of the following events, including but not limited to: disease progression precluding surgical treatment, local recurrence or distant metastasis, or death from any cause.
From start of study treatment up to approximately 3 years
Overall Survival(OS)
Time Frame: From start of study treatment up to approximately 5 years
The time from the start of study treatment to death from any cause.
From start of study treatment up to approximately 5 years
Organ Preservation Rate
Time Frame: At the time of surgery
The proportion of participants in whom the surgical approach is optimized or the extent of surgery is reduced after neoadjuvant therapy, as determined by experienced surgeons comparing the feasible surgical approach based on baseline tumor assessment prior to neoadjuvant therapy with the feasible surgical approach after completion of neoadjuvant therapy.
At the time of surgery
Surgery Postponement Rate
Time Frame: 6 weeks after neoadjuvant therapy
The proportion of subjects who did not undergo radical surgery within 6 weeks after the last dose of neoadjuvant therapy.
6 weeks after neoadjuvant therapy
Adverse Events (AEs)
Time Frame: From first dose of study treatment to 1 month after the last dose
Incidence, severity, and relationship to treatment of adverse events, as assessed by CTCAE criteria.
From first dose of study treatment to 1 month after the last dose

Collaborators and Investigators

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

Sponsor

Tianjin Medical University Cancer Institute and Hospital

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)

July 1, 2026

Primary Completion (Estimated)

October 31, 2027

Study Completion (Estimated)

December 31, 2030

Study Registration Dates

First Submitted

June 18, 2026

First Submitted That Met QC Criteria

June 18, 2026

First Posted (Actual)

June 24, 2026

Study Record Updates

Last Update Posted (Actual)

June 24, 2026

Last Update Submitted That Met QC Criteria

June 18, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RESERVE-HC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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