A Phase III Study of Becotatug Vedotin (MRG003) in Combination With PD-1 Inhibitor Versus PD-1 Inhibitor for the Treatment of EGFR-positive, CPS≥1 Resectable Locally Advanced Head and Neck Squamous Cell Carcinoma： a Multicenter, Randomized Controlled Trial
Overview
- Phase
- Phase 3
- Status
- Recruiting
- Sponsor
- Ming-Yuan Chen
- Enrollment
- 430
- Locations
- 1
- Primary Endpoint
- Event-Free Survival Rate (EFS)
Overview
Brief Summary
This study is a randomized, open-label, multicenter phase III trial designed to systematically evaluate the efficacy and safety of perioperative neoadjuvant and adjuvant therapy with Becotatug vedotin in combination with PD-1 inhibitor versus PD-1 inhibitor alone in patients with EGFR-positive, CPS ≥ 1 resectable locally advanced head and neck squamous cell carcinoma .
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Voluntarily sign the informed consent form;
- •Untreated, histologically confirmed head and neck squamous cell carcinoma (oral cavity, oropharynx, hypopharynx, or larynx), EGFR-positive, CPS ≥ 1, with clinical stage (AJCC 8th edition): p16-positive oropharynx: Stage III (T4N0-2M0); p16-negative oropharynx: Stage III or IVA; larynx/hypopharynx/oral cavity: Stage III or IVA;
- •Eligible for curative-intent surgery as determined by the surgeon;
- •Age: 18 to 75 years;
- •ECOG performance status 0-1;
- •Life expectancy greater than 6 months;
- •At least one measurable lesion per RECIST 1.1;
- •Adequate organ function, based on meeting all of the following criteria (no receipt of blood components or hematopoietic growth factors within 14 days prior to testing): hemoglobin ≥ 90 g/L; absolute neutrophil count ≥ 1.5 × 10⁹/L; platelet count ≥ 100 × 10⁹/L; serum albumin ≥ 28 g/L; total bilirubin ≤ 1.5 × upper limit of normal (ULN); ALT and AST ≤ 2.5 × ULN; serum creatinine ≤ 1.5 × ULN, with creatinine clearance ≥ 50 mL/min; activated partial thromboplastin time and international normalized ratio (INR) ≤ 1.5 × ULN (patients receiving a stable dose of anticoagulant therapy, such as low molecular weight heparin or warfarin, may be enrolled if INR is within the expected therapeutic range for the anticoagulant). Thyroid-stimulating hormone (TSH) ≤ ULN; if abnormal, T3 and T4 levels should be assessed, and patients with normal T3 and T4 levels may be enrolled;
- •Baseline left ventricular ejection fraction (LVEF) ≥ 50% as measured by multigated acquisition (MUGA) scan or echocardiography (ECHO);
- •Women of childbearing potential must agree to use contraception (e.g., intrauterine device, contraceptive pill, or condom) during the treatment period and for 3 months after the last dose;
Exclusion Criteria
- •Pregnant or breastfeeding women.
- •History of allergy to PD-1 inhibitors.
- •History of other malignancies within the past 5 years or at enrollment, with the exception of cured basal cell carcinoma of the skin, carcinoma in situ of the cervix, and thyroid papillary tumors.
- •Residual toxicity from prior anti-tumor therapy (including immunotherapy, targeted therapy, chemotherapy, or radiotherapy, etc.) other than alopecia, fatigue, and grade 2 hypothyroidism, or clinically significant laboratory abnormalities greater than grade 1 (CTCAE v5.0).
- •Uncontrolled cardiac conditions or diseases, such as: ① NYHA Class II or greater heart failure, ② unstable angina, ③ myocardial infarction within 1 year, and ④ patients with clinically significant ventricular arrhythmias requiring intervention.
- •Grade ≥ 2 peripheral neuropathy (per CTCAE v5.0).
- •Pulmonary embolism or deep vein thrombosis within 3 months prior to enrollment (excluding catheter-related thrombosis from infusion ports or PICC lines).
- •Active bleeding, history of coagulation disorders, or patients receiving coumarin anticoagulant therapy.
- •Known hypersensitivity to any component or excipient of vibecotamab (citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, sodium chloride, and polysorbate 80), or known grade ≥ 3 hypersensitivity reaction to other prior anti-EGFR agents (including investigational drugs) or other monoclonal antibodies.
- •Receipt of any of the following treatments:
Arms & Interventions
Becotatug vedotin plus pucotenlimab arm
Patients receive Becotatug vedotin combined with pucotenlimab as neoadjuvant treatment prior to surgical resection and as adjuvant treatment after radiotherapy.
Intervention: Neoadjuvant and Adjuvant Becotatug Vedotin (Drug)
Becotatug vedotin plus pucotenlimab arm
Patients receive Becotatug vedotin combined with pucotenlimab as neoadjuvant treatment prior to surgical resection and as adjuvant treatment after radiotherapy.
Intervention: Neoadjuvant and Adjuvant Immunotherapy (Drug)
Becotatug vedotin plus pucotenlimab arm
Patients receive Becotatug vedotin combined with pucotenlimab as neoadjuvant treatment prior to surgical resection and as adjuvant treatment after radiotherapy.
Intervention: Surgery (Procedure)
Becotatug vedotin plus pucotenlimab arm
Patients receive Becotatug vedotin combined with pucotenlimab as neoadjuvant treatment prior to surgical resection and as adjuvant treatment after radiotherapy.
Intervention: Adjuvant Radiotherapy (Radiation)
pucotenlimab arm
Patients receive pucotenlimab as neoadjuvant treatment prior to surgical resection and as adjuvant duiring and after radiotherapy.
Intervention: Neoadjuvant and Adjuvant Immunotherapy (Drug)
pucotenlimab arm
Patients receive pucotenlimab as neoadjuvant treatment prior to surgical resection and as adjuvant duiring and after radiotherapy.
Intervention: Surgery (Procedure)
pucotenlimab arm
Patients receive pucotenlimab as neoadjuvant treatment prior to surgical resection and as adjuvant duiring and after radiotherapy.
Intervention: Adjuvant Radiotherapy (Radiation)
pucotenlimab arm
Patients receive pucotenlimab as neoadjuvant treatment prior to surgical resection and as adjuvant duiring and after radiotherapy.
Intervention: Adjuvant Cisplatin (Drug)
Becotatug vedotin plus pucotenlimab arm
Patients receive Becotatug vedotin combined with pucotenlimab as neoadjuvant treatment prior to surgical resection and as adjuvant treatment after radiotherapy.
Intervention: Adjuvant Cisplatin (Drug)
Outcomes
Primary Outcomes
Event-Free Survival Rate (EFS)
Time Frame: 3 years
Defined as the time from randomization to the first occurrence of disease progression, relapse, or death from any cause.
Secondary Outcomes
- Overall Survival (OS)(3 years)
- Distant Metastasis-Free Survival (DMFS)(3 years)
- Locoregional Relapse-Free Survival (LRRFS)(3 years)
- Objective Response Rate (ORR)(After the completion of neoadjuvant therapy, prior to surgery.)
- Disease Control Rate (DCR)(After the completion of neoadjuvant therapy, prior to surgery.)
- Major Pathologic Response Rate (mPR):(1 week post-surgery)
- Pathologic Complete Response Rate (pCR)(1 week post-surgery)
- Incidence of treatment related acute complications(up to 1 year)
- Incidence of treatment related late complications(up to 3 years)
- Non-Surgery Delay Rate(8 weeks after two cycles of neoadjuvant therapy)
- R0 Resection Rate(1 week post-surgery.)
- General Quality of Life(Baseline, week 4 (post-neoadjuvant), week 6 (preoperative), week 8 (postoperative), week 10 (pre-radiotherapy), week 17 (post-radiotherapy), every 2 cycles of adjuvant therapy (each cycle is 21 days), and at each follow-up, up to 3 years)
- Head and Neck Cancer-Specific Quality of Life(Baseline, week 4 (post-neoadjuvant), week 6 (preoperative), week 8 (postoperative), week 10 (pre-radiotherapy), week 17 (post-radiotherapy), every 2 cycles of adjuvant therapy (each cycle is 21 days), and at each follow-up, up to 3 years.)
Investigators
Ming-Yuan Chen
Professor, Chief physician
Sun Yat-sen University