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

Official title

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

Overview

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

Interventions

• Drug Becotatug Vedotin for Injection
  Administrated intravenously
• Drug Placebo
  Administrated intravenously
• Drug Pucotenlimab Injection
  Administrated intravenously

Primary outcome measures

• Major Pathological Response (MPR) Rate [Time frame: From date of surgery until completion of postoperative pathological assessment, up to 8 weeks]

Secondary outcome measures (10)

• Pathological Complete Response (pCR) Rate [Time frame: From date of surgery until completion of postoperative pathological assessment, up to 8 weeks]
• Event-Free Survival (EFS) [Time frame: 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) [Time frame: From date of randomization until death from any cause, assessed up to 36 months]
• Preoperative Objective Response Rate (ORR) [Time frame: preoperative ORR will be assessed up to 12 weeks post-randomization]
• actual surgical resection rate [Time frame: surgical resection rate will be evaluated perioperatively]
• R0 resection rate [Time frame: R0 resection rate will be confirmed up to 8 weeks postoperatively]
• lymph node downstaging rate [Time frame: 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 [Time frame: Within 30 days after last dose (30 days + 7 days window)]
• Serum Concentration [Time frame: From randomization through completion of therapy, up to 30 weeks]
• Incidence of Anti-Drug Antibodies (ADA) [Time frame: From randomization through completion of therapy, up to 30 weeks]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

• Primary tumor originating from nasopharynx, nasal cavity, paranasal sinuses, salivary gland, thyroid/parathyroid gland, skin, or unknown primary site (squamous cell carcinoma).
• Head and neck cancer deemed non-resectable by the investigator.
• Prior treatment with anti-PD-1, anti-PD-L1, MMAE/MMAF-based ADC agents, or other T-cell immune checkpoint inhibitors.
• Prior radiotherapy, systemic anti-tumor therapy, or other investigational therapy for head and neck cancer before study entry.
• 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.
• Grade ≥2 peripheral neuropathy (CTCAE v5.0).
• Active autoimmune disease requiring systemic treatment within 2 years before first dose.
• Receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy within 2 weeks before first dose.
• Radiologically detectable central nervous system metastases and/or carcinomatous meningitis.
• Uncontrolled pleural, peritoneal, pelvic effusion, or pericardial effusion.
• Any severe or uncontrolled systemic disease.
• Prior or planned allogeneic tissue/solid organ transplantation.
• Known hypersensitivity to any active ingredient or excipient of the study drugs.
• Evidence of active infection including hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
• Anti-infective therapy within 2 weeks before randomization.
• Stroke or transient ischemic attack within 6 months before enrollment.
• Uncontrolled or poorly controlled cardiac disease.
• Deep or intraluminal bleeding requiring interventional/surgical hemostasis or blood transfusion within 3 months, or current history of coagulopathy.
• Pulmonary embolism or deep vein thrombosis within 3 months.
• History of or current interstitial lung disease, severe chronic obstructive pulmonary disease, severe pulmonary insufficiency, bronchospasm, etc.
• Received live vaccine within 30 days before first study dose.
• History of other primary malignancy.
• Positive serum pregnancy test or breastfeeding female.
• Contraindications to study drugs (pucotenlimab and/or becotatug vedotin) or their excipients; severe hypersensitivity (Grade ≥3) to radiotherapy, cisplatin or its analogues.
• Any condition that the investigator considers unsuitable for participation in the trial.
• Grade ≥2 hearing impairment per CTCAE v6.0.

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

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 15 centers

• Peking University Cancer Hospital — Beijing
• The First Affiliated Hospital of Fujian Medical University — Fuzhou
• Sun Yat-sen University Cancer Center — Guangzhou
• Sun Yat-sen Memorial Hospital, Sun Yat-sen University — Guangzhou
• Cancer Hospital of Shantou University Medical College — Shantou
• Guangxi Medical University Cancer Hospital — Nanning
• The Fourth Hospital of Hebei Medical University — Shijiazhuang
• Hubei Cancer Hospital — Wuhan
• … and 7 more centers

Identifiers

NCT: NCT07586124 · HX008/MRG003-C004

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗