Head and Neck Squamous Cell Carcinoma
Conditions
Keywords
Pucotenlimab, Becotatug Vedotin
Brief summary
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
DRUGBecotatug Vedotin for Injection
Administrated intravenously
DRUGPlacebo
Administrated intravenously
DRUGPucotenlimab Injection
Administrated intravenously
Sponsors
Lepu Biopharma Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Major Pathological Response (MPR) Rate | From date of surgery until completion of postoperative pathological assessment, up to 8 weeks |
Secondary
| 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 |
Countries
China
Contacts
CONTACTProgram Director
Outcome results
None listed