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

Official title

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

Overview

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.

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.

Interventions

• 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 c

Primary outcome measures

• Pathological Complete Response(pCR) Rate [Time frame: At the time of surgery]

Secondary outcome measures (7)

• Major Pathological Response(MPR) Rate [Time frame: At the time of surgery]
• Objective Response Rate（ORR） [Time frame: 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]
• Overall Survival(OS) [Time frame: From start of study treatment up to approximately 5 years]
• Organ Preservation Rate [Time frame: At the time of surgery]
• Surgery Postponement Rate [Time frame: 6 weeks after neoadjuvant therapy]
• Adverse Events (AEs) [Time frame: From first dose of study treatment to 1 month after the last dose]

Eligibility criteria

Inclusion criteria

• Aged ≥ 18, male or female;
• Histopathologically confirmed Hypopharyngeal Squamous Cell Carcinoma;
• 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

• Patients with distant metastasis;
• Patients with uncontrolled severe medical conditions;
• Patients with a history of allergy or hypersensitivity to any component of monoclonal antibody therapies;
• Uncontrolled cardiac clinical symptoms or diseases;
• Occurrence of severe infection (CTCAE Grade > 2) within 4 weeks prior to the first dose of the study drug;
• Unexplained fever > 38.5°C during the screening period or before the first dose;
• Active autoimmune disease or a history of autoimmune disease;
• History of immunodeficiency, or a history of organ transplantation or allogeneic bone marrow transplantation;
• 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;
• History of interstitial lung disease;
• Patients with active pulmonary tuberculosis infection identified by medical history or CT scan;
• 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;

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Tianjin Medical University Cancer Institute and Hospital, Tianjin, Tianjin 300000 — Tianjin

Identifiers

NCT: NCT07665190 · RESERVE-HC

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗