Pucotenlimab Plus Becotatug Vedotin in Perioperative Treatment of Locally Advanced Resectable Head and Neck Squamous Cell Carcinoma

A Multicenter, Randomized, Double-Blind, Phase II Clinical Study of Pucotenlimab Injection Combined With Becotatug Vedotin for Injection as Perioperative Therapy in Participants With Locally Advanced Resectable Head and Neck Squamous Cell Carcinoma

A multicenter, randomized, double-blind, phase II clinical study designed to evaluate the safety, pharmacokinetics, and preliminary efficacy of Becotatug Vedotin for Injection in combination with PD-1 in patients with locally advanced resectable head and neck squamous cell carcinoma

Study Overview

• Status: Not yet recruiting
• Conditions: Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Becotatug Vedotin for Injection; Drug: Pucotenlimab Injection; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Program Director; Phone Number: 86-21- 67680899; Email: ra_bj@lepubiopharma.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Peking University Cancer Hospital
      • Contact: Bin Zhang
  • Fujian
    • Fuzhou, Fujian, China, 350005
      • The First Affiliated Hospital of Fujian Medical University
      • Contact: Gongbiao Lin
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun yat-sen University Cancer Center
      • Contact: Xuekui Liu
    • Guangzhou, Guangdong, China, 510120
      • Sun Yat-sen Memorial Hospital, Sun Yat-sen University
      • Contact: Jinsong Li
    • Shantou, Guangdong, China, 515041
      • Cancer Hospital of Shantou University Medical College
      • Contact: Hanwei Peng
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • Guangxi Medical University Cancer Hospital
      • Contact: Duoping Wang
  • Hebei
    • Shijiazhuang, Hebei, China, 050011
      • The Fourth Hospital of Hebei Medical University
      • Contact: Juan Li
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital
      • Contact: Jian Chen
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital
      • Contact: Hao Tian
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital of Central South University
      • Contact: Canhua Jiang
  • Liaoning
    • Shenyang, Liaoning, China, 110042
      • Liaoning Cancer Hospital & Institute
      • Contact: Zhendong Li
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200120
      • Shanghai East Hospital
      • Contact: Ye Guo
    • Shanghai, Shanghai Municipality, China, 200011
      • Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine
      • Contact: Yue He
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital
      • Contact: Chao Chen
    • Ningbo, Zhejiang, China, 315040
      • Ningbo Medical Center Lihuili Hospital
      • Contact: Zhisen Shen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Life expectancy ≥ 6 months.
2. Subjects with histologically confirmed, resectable Stage III-IVA head and neck squamous cell carcinoma (HNSCC) eligible for curative-intent surgery.
3. At least one extracranial measurable lesion per RECIST v1.1.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
5. No severe cardiac dysfunction.
6. Must provide tumor tissue sample not previously subjected to radiotherapy.
7. Adequate organ function.
8. Subjects of childbearing potential must use effective contraception during the study and for 180 days after the last dose.

Exclusion Criteria:

1. Primary tumor originating from nasopharynx, nasal cavity, paranasal sinuses, salivary gland, thyroid/parathyroid gland, skin, or unknown primary site (squamous cell carcinoma).
2. Head and neck cancer deemed non-resectable by the investigator.
3. Prior treatment with anti-PD-1, anti-PD-L1, MMAE/MMAF-based ADC agents, or other T-cell immune checkpoint inhibitors.
4. Prior radiotherapy, systemic anti-tumor therapy, or other investigational therapy for head and neck cancer before study entry.
5. Major surgery within 4 weeks before study entry, or not fully recovered from surgical toxicities/complications. Minor procedures (e.g., vascular access placement, percutaneous/endoscopic head/neck biopsy, tracheostomy tube exchange) are allowed.
6. Grade ≥2 peripheral neuropathy (CTCAE v5.0).
7. Active autoimmune disease requiring systemic treatment within 2 years before first dose.
8. Receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy within 2 weeks before first dose.
9. Radiologically detectable central nervous system metastases and/or carcinomatous meningitis.
10. Uncontrolled pleural, peritoneal, pelvic effusion, or pericardial effusion.
11. Any severe or uncontrolled systemic disease.
12. Prior or planned allogeneic tissue/solid organ transplantation.
13. Known hypersensitivity to any active ingredient or excipient of the study drugs.
14. Evidence of active infection including hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
15. Anti-infective therapy within 2 weeks before randomization.
16. Stroke or transient ischemic attack within 6 months before enrollment.
17. Uncontrolled or poorly controlled cardiac disease.
18. Deep or intraluminal bleeding requiring interventional/surgical hemostasis or blood transfusion within 3 months, or current history of coagulopathy.
19. Pulmonary embolism or deep vein thrombosis within 3 months.
20. History of or current interstitial lung disease, severe chronic obstructive pulmonary disease, severe pulmonary insufficiency, bronchospasm, etc.
21. Received live vaccine within 30 days before first study dose.
22. History of other primary malignancy.
23. Positive serum pregnancy test or breastfeeding female.
24. Contraindications to study drugs (pucotenlimab and/or becotatug vedotin) or their excipients; severe hypersensitivity (Grade ≥3) to radiotherapy, cisplatin or its analogues.
25. Any condition that the investigator considers unsuitable for participation in the trial.
26. Grade ≥2 hearing impairment per CTCAE v6.0.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: locally advanced resectable HNSCC Becotatug Vedotin +Pucotenlimab	Drug: Becotatug Vedotin for Injection; Administrated intravenously; Drug: Pucotenlimab Injection; Administrated intravenously
Placebo Comparator: locally advanced resectable HNSCC Placebo +Pucotenlimab	Drug: Pucotenlimab Injection; Administrated intravenously; Drug: Placebo; Administrated intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Major Pathological Response (MPR) Rate	From date of surgery until completion of postoperative pathological assessment, up to 8 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Pathological Complete Response (pCR) Rate	From date of surgery until completion of postoperative pathological assessment, up to 8 weeks
Event-Free Survival (EFS)	From date of randomization until the date of disease progression/recurrence with initiation of new anti-tumor therapy, or death from any cause, whichever came first, assessed up to 24 months
Overall Survival (OS)	From date of randomization until death from any cause, assessed up to 36 months
Preoperative Objective Response Rate (ORR)	preoperative ORR will be assessed up to 12 weeks post-randomization
actual surgical resection rate	surgical resection rate will be evaluated perioperatively
R0 resection rate	R0 resection rate will be confirmed up to 8 weeks postoperatively
lymph node downstaging rate	lymph node downstaging rate will be determined up to 8 weeks postoperatively based on comparison of pre- and post-treatment imaging and pathology
Incidence of adverse events (AEs) and laboratory abnormalities assessed by CTCAE v6.0	Within 30 days after last dose (30 days + 7 days window)
Serum Concentration	From randomization through completion of therapy, up to 30 weeks
Incidence of Anti-Drug Antibodies (ADA)	From randomization through completion of therapy, up to 30 weeks

Collaborators and Investigators

• Sponsor: Lepu Biopharma Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: April 30, 2026
• First Submitted That Met QC Criteria: May 7, 2026
• First Posted (Actual): May 14, 2026

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Pucotenlimab; Becotatug Vedotin
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Therapeutics; Drug Administration Routes; Drug Therapy; Injections
• Other Study ID Numbers: HX008/MRG003-C004

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