MRG003 Plus Toripalimab Versus Toripalimab as Neoadjuvant Therapy for PD-L1-Positive, Resectable, Locally Advanced Head and Neck Squamous Cell Carcinoma

NCT07677475 | Not Yet Recruiting Phase 2

• 1 other identifier: IIT-2026-008
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, prospective, randomized, controlled Phase II trial evaluating the safety and efficacy of MRG003 (Becotatug vedotin) combined with Toripalimab versus Toripalimab alone as neoadjuvant therapy for PD-L1-positive, resectable locally advanced head and neck squamous cell carcinoma. A total of 65 subjects are planned (43 experimental, 22 control). The experimental arm receives two cycles of MRG003 (Becotatug vedotin) 2.0 mg/kg intravenously on Day 1 followed by Toripalimab 240 mg intravenously on Day 1 every 3 weeks, while the control arm receives two cycles of Toripalimab 240 mg alone. After neoadjuvant therapy, both arms undergo radical surgery 3-4 weeks later, followed by risk-adapted adjuvant radiotherapy or chemoradiotherapy with concurrent Toripalimab (3 cycles) and then 12 cycles of adjuvant Toripalimab maintenance. The primary endpoint is the major pathological response rate.

Conditions

Head and Neck Squamous Cell Carcinoma

Keywords

MRG003; Vebecototagene Autoleucovorin; Toripalimab; Neoadjuvant Therapy

Outcome Measures

Primary Outcomes (1)

• Major Pathological Response (MPR) rate

  Proportion of patients with major pathological response, defined as ≤ 10% residual viable tumor in the primary tumor and all sampled lymph nodes after completion of neoadjuvant therapy.

  At the time of surgical specimen evaluation (approximately 6-8 weeks after initiation of neoadjuvant therapy)

Secondary Outcomes (6)

• Event-Free Survival (EFS)

  From randomization up to approximately 36 months

• Pathologic Complete Response (pCR) Rate

  At definitive surgery (approximately Week 6-8 after randomization)

• Objective Response Rate (ORR) per RECIST 1.1

  After completion of 2 cycles of neoadjuvant therapy (approximately Week 6)

• Safety: Incidence of Adverse Events and Serious Adverse Events

  From first dose of study drug through 90 days after last dose or 30 days after surgery, whichever occurs later

• On-Time Surgery Rate

  Within 49 days after Cycle 2 Day 1（ (each cycle is 21 days)）

Study Arms (2)

MRG003 + Toripalimab

EXPERIMENTAL

Participants receive 2 cycles of neoadjuvant combination therapy with toripalimab plus MRG003 (Becotatug vedotin). After the neoadjuvant phase, radical surgery is performed. Postoperative management follows the same risk-adapted criteria as the control arm: participants with ENE or positive/inadequate margins receive adjuvant chemoradiotherapy, while those without receive adjuvant radiotherapy alone. During adjuvant radiotherapy, participants receive 3 cycles of concurrent toripalimab. After radiotherapy, all participants receive 12 cycles of adjuvant toripalimab maintenance therapy.

Drug: MRG003 (Becotatug vedotin) and Toripalimab; Drug: Toripalimab

Toripalimab Monotherapy

ACTIVE COMPARATOR

Participants receive 2 cycles of neoadjuvant toripalimab monotherapy. After the neoadjuvant phase, radical surgery is performed. Postoperative management is determined by pathology: participants with extranodal extension (ENE) or positive/inadequate margins receive adjuvant chemoradiotherapy (cisplatin 100 mg/m² every 3 weeks for 3 cycles plus radiotherapy at 60-70 Gy depending on risk), while those without receive adjuvant radiotherapy alone. During adjuvant radiotherapy, participants receive 3 cycles of concurrent toripalimab. After radiotherapy, all participants receive 12 cycles of adjuvant toripalimab maintenance therapy.

Drug: Toripalimab

Interventions

Toripalimab DRUG

Toripalimab 240 mg administered intravenously over 30-60 minutes on Day 1 of each 3-week cycle. Neoadjuvant phase: 2 cycles. Adjuvant phase (concurrent with radiotherapy): 3 cycles. Adjuvant maintenance (after radiotherapy): 12 cycles. No prophylactic premedication required. No dose modification of toripalimab is permitted.

MRG003 + Toripalimab; Toripalimab Monotherapy

MRG003 (Becotatug vedotin) and Toripalimab DRUG

Toripalimab 240 mg administered intravenously over 30-60 minutes on Day 1 of each 3-week cycle, followed immediately by MRG003 (Becotatug vedotin) 2.0 mg/kg (based on actual body weight) administered intravenously without prophylactic premedication. Neoadjuvant phase: 2 cycles of both drugs. Adjuvant toripalimab: 3 cycles concurrent with radiotherapy, then 12 cycles maintenance. For MRG003 (Becotatug vedotin), monitor infusion reactions for at least 120 minutes after first dose and at least 60 minutes after subsequent doses if tolerated. Dose reduction of MRG003 (Becotatug vedotin) to 1.5 mg/kg is permitted once for toxicity; permanent discontinuation if intolerance persists at reduced dose. Toripalimab dose remains fixed throughout; no dose modification is permitted.

MRG003 + Toripalimab

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

1. Histologically or cytologically confirmed head and neck squamous cell carcinoma (HNSCC), PD-L1 positive (CPS ≥ 1) 2. Treatment-naïve, pathologically confirmed stage III-IVA resectable non-oropharyngeal HNSCC (oral cavity, larynx, hypopharynx) OR HPV-negative oropharyngeal SCC, OR HPV-positive stage III T4N0-2 resectable oropharyngeal cancer (AJCC 8th edition) 3. No prior antitumor treatment (radiotherapy, chemotherapy, targeted therapy, or immunotherapy) 4. Age 18 to 70 years 5. ECOG performance status 0 or 1 6. Adequate organ function within 14 days before first dose (no blood products or growth factors within 14 days): * ANC ≥ 1.0 × 10⁹/L, Hb ≥ 90 g/L, PLT ≥ 75 × 10⁹/L * ALT/AST ≤ 1.5 × ULN, total bilirubin ≤ 1.5 × ULN, ALP \< 2.5 × ULN * CrCl ≥ 50 mL/min (Cockcroft-Gault) * APTT and INR ≤ 1.5 × ULN 7. At least one measurable lesion per RECIST 1.1 8. Life expectancy ≥ 12 weeks 9. Female subjects of childbearing potential and male subjects with reproductive potential must use medically accepted contraception during treatment and for 3 months after last dose 10. Voluntary signed informed consent, good compliance, willing to undergo follow-up

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Dongguan People's Hospital: lead
• Sun Yat-Sen University Cancer Center: collaborator
• Shenzhen People's Hospital: collaborator
• Peking University Shenzhen Hospital: collaborator
• The University of Hong Kong-Shenzhen Hospital: collaborator
• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: collaborator
• Huizhou Municipal Central Hospital: collaborator
• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: collaborator

Study Sites (1)

The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital)

Dongguan, Guangdong, 523059, China

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

toripalimab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Study Officials

• Zhigang Liu, MD

  The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital)

  STUDY CHAIR

Central Study Contacts

Liji Jiang, Master

CONTACT

0769-28637916; keynotejiang@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: This is a randomized, parallel-arm, open-label, Phase 2 clinical trial. Eligible patients are randomized in a 2:1 ratio to receive either neoadjuvant MRG003 (Becotatug vedotin) plus toripalimab (Experimental Arm) or neoadjuvant toripalimab monotherapy (Control Arm).

Study Record Dates

• First Submitted: June 23, 2026
• First Posted: June 30, 2026
• Study Start: June 30, 2026
• Primary Completion (Estimated): January 30, 2029
• Study Completion (Estimated): June 30, 2029
• Last Updated: July 31, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)