A Prospective, Exploratory Study of Becotatug Vedotin Plus Putlimab for Neoadjuvant Therapy and Adjuvant Radiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma

NCT07707167 | Not Yet Recruiting Phase 2

• 1 other identifier: EGFR-ADC-LA-HNSCC
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, exploratory, non-registration, multi-center clinical study to evaluate the efficacy and safety of becotatug vedotin (EGFR-ADC) combined with putlimab and radiotherapy in the perioperative treatment of locally advanced resectable head and neck squamous cell carcinoma (HNSCC). \*\*Neoadjuvant Phase\*\* (3-week cycle, 2 cycles):

• Putlimab (HX008): 200 mg, Q3W, D1, IV
• Becotatug vedotin (MRG003): 2.0 mg/kg, Q3W, D1, IV \*\*Adjuvant/Maintenance Phase:\*\* Surgery within 2-4 weeks post-neoadjuvant; surgical approach at investigator discretion. \*\*Group A (Postoperative pCR):\*\*
• Putlimab (HX008): 200 mg, Q3W, D1, IV, up to 1 year
• Adjuvant RT: 40 Gy/5 weeks \*\*Group B (Postoperative MPR):\*\*
• Putlimab (HX008): 200 mg, Q3W, D1, IV, up to 1 year
• Adjuvant RT: 50 Gy/5 weeks \*\*Group C (Postoperative Partial/No Response):\*\*
• Low-risk (no extracapsular nodal extension \[ENE\] and negative margins): Putlimab 200 mg Q3W (up to 1 year) + RT 60 Gy/6 weeks
• High-risk (ENE and/or positive margins): Putlimab 200 mg Q3W (up to 1 year) + RT 60-66 Gy/6-6.6 weeks + Cisplatin 60 mg/m², Q3W, D1, IV, for 2 cycles RT timing, field, and fractionation may be adjusted by investigators based on individual disease status. Imaging assessment every 2 cycles (±7 days) until disease recurrence, initiation of new anti-tumor therapy, withdrawal of informed consent, death, or up to 21 cycles, whichever occurs first. Additional imaging may be performed at any time if clinically indicated.

Conditions

LA HNSCC

Keywords

Becotatug vedotin; Pucotenlimab; Sequential radiotherapy

Outcome Measures

Primary Outcomes (1)

• Pathologic response

  Periprocedural

Secondary Outcomes (6)

• Major pathological response

  Periprocedural

• Objective Response Rate

  At the end of Cycle 2 (each cycle is 21 days)

• Disease Control Rate

  At the end of Cycle 2 (each cycle is 21 days)

• Event-Free Survival

  2 years after surgery

• Overall survival

  2 years after surgery

Study Arms (1)

Experimental

EXPERIMENTAL

Neoadjuvant Phase: All subjects will receive 2 cycles of Becotatug vedotin (MRG003): 2.0 mg/kg, Q3W, D1, IV; and Putlimab (HX008): 200 mg, Q3W, D1, IV. Adjuvant Phase: All subjects will receive Putlimab for up to 1 year, with varying degrees of chemoradiotherapy added based on each subject's pathological response and nodal involvement status.

Drug: Pucotenlimab; Drug: Becotatug vedotin; Radiation: Radiotherapy

Interventions

Pucotenlimab DRUG

Neoadjuvant Phase: All subjects will receive 2 cycles of Putlimab (HX008): 200 mg, Q3W, D1, IV (60 ± 15 min, first cycle infusion ≥ 60 min). Adjuvant Phase: All subjects will receive Putlimab for up to 1 year，200 mg, Q3W, D1, IV (60 ± 15 min, first cycle infusion ≥ 60 min).

Experimental

Becotatug vedotin DRUG

Neoadjuvant Phase: All subjects will receive 2 cycles of Becotatug vedotin (MRG003): 2.0 mg/kg, Q3W, D1, IV(60 ± 15 min, first cycle infusion ≥ 60 min).

Experimental

Radiotherapy RADIATION

Adjuvant Phase: All subjects will receive varying degrees of chemoradiotherapy based on their pathological response and nodal involvement status. Group A (Postoperative pCR): RT 40 Gy/5 weeks. \*\*Group B (Postoperative MPR): RT 50 Gy/5 weeks.；Group C (Postoperative Partial Response/No Response): (1) Low/Intermediate-risk subjects (no extracapsular nodal extension \[ENE\] and negative margins): RT 60 Gy/6 weeks; (2) High-risk subjects (ENE and/or positive margins): RT 60-66 Gy/6-6.6 weeks combined with cisplatin. RT timing, field, and fractionation may be adjusted by investigators based on individual disease status.

Experimental

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of any malignancy other than gastric cancer within 5 years prior to the first dose, with the exception of adequately treated cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, and/or radically resected carcinoma in situ;
• Known endoscopic evidence of active bleeding in the target lesion;
• Concurrent participation in another interventional clinical study, or receipt of any investigational medicinal product or use of investigational device within 4 weeks prior to the first dose;
• Prior exposure to any of the following therapies: anti-PD-1, anti-PD-L1, or anti-PD-L2 agents; agents targeting other stimulatory or co-inhibitory T-cell receptors (including but not limited to CTLA-4, OX-40, and CD137); or antibody-drug conjugates (ADCs) with MMAE or MMAF payloads;
• Systemic administration of Chinese proprietary medicines with anti-tumor indications or immunomodulatory agents (including thymosin, interferon, and interleukins, except for local administration to control pleural effusion) within 2 weeks prior to the first dose;
• Active autoimmune disease requiring systemic therapy (e.g., disease-modifying antirheumatic drugs, corticosteroids, or immunosuppressants) within 2 years prior to the first dose. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement for adrenal or pituitary insufficiency) is not considered systemic therapy;
• Receipt of systemic corticosteroid therapy (excluding intranasal, inhaled, or other topical corticosteroids) or any other form of immunosuppressive therapy within 7 days prior to the first dose; \*Note: Physiologic doses of corticosteroids (prednisone ≤10 mg/day or equivalent) are permitted;\*
• History of allogeneic organ transplantation (corneal transplantation excluded) or allogeneic hematopoietic stem cell transplantation;
• Known hypersensitivity to pucotenlimab, MRG003, or any of their excipients;
• Failure to recover adequately from toxicities and/or complications of prior interventions (i.e., to Grade ≤1 or to baseline, excluding fatigue and alopecia) prior to initiation of study treatment;
• Known history of human immunodeficiency virus (HIV) infection (HIV-1/2 antibody positive);
• Untreated active hepatitis B infection (defined as HBsAg positivity with HBV-DNA copy number above the upper limit of normal of the local laboratory); \*Note: Subjects with hepatitis B may be enrolled if they meet the following criteria:\* 1) HBV viral load \<1,000 copies/mL (200 IU/mL) prior to the first dose; subjects must receive prophylactic anti-HBV therapy throughout the study treatment period to prevent viral reactivation; 2) Subjects with anti-HBc (+), HBsAg (-), anti-HBs (-), and undetectable HBV viral load are not required to receive prophylactic anti-HBV therapy but require close monitoring for viral reactivation;
• Active hepatitis C infection (HCV antibody positive with HCV-RNA level above the lower limit of quantification);
• Receipt of a live vaccine within 30 days prior to Cycle 1 Day 1; \*Note: Inactivated injectable influenza vaccines for seasonal influenza are permitted within 30 days prior to the first dose; intranasal live-attenuated influenza vaccines are not permitted;\*
• Pregnancy or breastfeeding;

You may not qualify if:

• Presence of distant metastatic lesions;
• History of Grade ≥3 immune-related adverse events or treatment-related adverse events that have not recovered to Grade ≤1;
• Receipt of surgery, chemotherapy, targeted small molecule therapy, or radiotherapy for another invasive malignancy within the past 5 years;
• Autoimmune disease requiring systemic corticosteroid therapy within the past 3 months, history of clinically significant autoimmune disease, or syndrome requiring systemic corticosteroid therapy;
• Active infection requiring systemic treatment;
• Prior receipt of any form of anti-tumor therapy for the primary tumor or metastatic lymph nodes, including chemotherapy, radiotherapy, targeted therapy, anti-PD-1 or anti-PD-L1 therapy, or surgery (biopsy excluded);
• History of other malignancies;
• History of organ transplantation;
• History of autoimmune disease, or other conditions requiring long-term systemic corticosteroid or immunosuppressive therapy;
• Positive for human immunodeficiency virus (HIV);
• Active hepatitis B or hepatitis C infection (HBV DNA or HCV RNA above the upper limit of normal);
• Total white blood cell count \<3.5×10⁹/L, absolute lymphocyte count \<0.8×10⁹/L, neutrophil count \<1.5×10⁹/L, platelet count \<100×10⁹/L, or hemoglobin \<90 g/L; total bilirubin \>1.5× upper limit of normal (ULN), transaminases (AST, ALT) \>3× ULN (\>5× ULN if hepatic metastases present), serum creatinine \>1.5× ULN; coagulation abnormalities with international normalized ratio (INR) or prothrombin time (PT) \>1.5× ULN;
• Serious cardiovascular, respiratory, or major immune system comorbidities; including urinary tract obstruction, myocardial infarction, arrhythmia, obstructive or restrictive lung disease, or other conditions that the Investigator considers may increase subject risk;
• Pregnant or lactating women;
• Refusal to use effective contraception during the treatment period and for 3 months thereafter;

Sponsors & Collaborators

• Jiangsu Cancer Institute & Hospital: lead

Study Sites (1)

Jiangsu Cancer Hospital

Nanjing, China

Location

MeSH Terms

Interventions

Radiotherapy

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

WuLi MD Rong

CONTACT

+86-13701588737; wulirong126@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Neoadjuvant Phase: All subjects will receive 2 cycles of Becotatug vedotin (MRG003): 2.0 mg/kg, Q3W, D1, IV; and Putlimab (HX008): 200 mg, Q3W, D1, IV. Adjuvant Phase: All subjects will receive Putlimab for up to 1 year, with varying degrees of chemoradiotherapy added based on each subject's pathological response and nodal involvement status.

Study Record Dates

• First Submitted: July 8, 2026
• First Posted: July 16, 2026
• Study Start (Estimated): August 31, 2026
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): January 31, 2029
• Last Updated: July 16, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)