A Prospective, Single-Arm, Phase II Clinical Study of Neoadjuvant Therapy With Pucotenlimab, Lenvatinib, and Temozolomide for Resectable Head and Neck Mucosal Melanoma (PLT-NAT-HNMM-II)

NCT07353073 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: SH9H-2025-T534-1
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to conduct a prospective clinical trial investigating the use of pucotenlimab in combination with lenvatinib and temozolomide as neoadjuvant and postoperative adjuvant therapy for resectable oral and head and neck mucosal melanoma. The primary objectives are to evaluate the safety and efficacy of this combination regimen in the neoadjuvant treatment of head and neck mucosal melanoma.

Conditions

Head and Neck Mucosal Melanomas

Keywords

head and neck mucosal melanoma; pucotenlimab

Outcome Measures

Primary Outcomes (1)

• Pathological Response Rate (pCR + Near-pCR + pPR).

  pCR (Pathological Complete Response, no residual tumor), near-pCR (Near Pathological Complete Response, tumor residue ≤10%), pPR (Pathological Partial Response, 10% \< tumor residue ≤50%), and pNR (Pathological No Response, tumor residue \>50%).

  Preoperatively, within 2-4 weeks after completing neoadjuvant therapy

Secondary Outcomes (3)

• Pathologic Complete Response (pCR) Rate

  Preoperatively, within 2-4 weeks after completing neoadjuvant therapy

• objective response rate

  4-8 weeks

• adverse event (AE)

  1 year

Study Arms (1)

pucotenlimab in combination with lenvatinib and temozolomide

EXPERIMENTAL

Preoperatively, patients will receive 2 cycles of pucotenlimab (200 mg every 3 weeks, or 3 mg/kg every 3 weeks) combined with lenvatinib (20 mg once daily) and temozolomide (150 mg/m² orally once daily for 5 consecutive days per 28-day cycle). Postoperatively, treatment with pucotenlimab will be continued until a total of 1 year of therapy is completed.

Drug: Preoperatively, patients will receive 2 cycles of pucotenlimab (200 mg every 3 weeks, or 3 mg/kg every 3 weeks) combined with lenvatinib (20 mg once daily) and temozolomide (150 mg/m² orally once dail

Interventions

Preoperatively, patients will receive 2 cycles of pucotenlimab (200 mg every 3 weeks, or 3 mg/kg every 3 weeks) combined with lenvatinib (20 mg once daily) and temozolomide (150 mg/m² orally once dail DRUG

Preoperatively, patients will receive 2 cycles of pucotenlimab (200 mg every 3 weeks, or 3 mg/kg every 3 weeks) combined with lenvatinib (20 mg once daily) and temozolomide (150 mg/m² orally once daily for 5 consecutive days per 28-day cycle). Postoperatively, treatment with pucotenlimab will be continued until a total of 1 year of therapy is completed.

pucotenlimab in combination with lenvatinib and temozolomide

Eligibility Criteria

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

You may qualify if:

• Age 18 to 75 years, regardless of gender.
• Histologically confirmed primary, resectable Head and Neck Mucosal Melanoma (HNMM), with measurable lesions (spiral CT scan ≥10 mm, meeting RECIST 1.1 criteria) or intraoral patch lesions deemed evaluable by the study investigators.
• ECOG performance status of 0 or 1.
• Life expectancy ≥12 weeks.
• At least one measurable lesion according to RECIST 1.1 criteria. Previously treated lesions can also serve as target lesions if disease progression has occurred.
• Availability of tumor tissue for PD-L1 testing (paraffin-embedded specimens from within the last 2 years or fresh tumor tissue).
• Organ function must meet the following requirements (within 14 days prior to the first dose of the study drug):
• \*\*Bone Marrow:\*\* Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L, platelet count (PLT) ≥100 × 10⁹/L, hemoglobin (HB) ≥9 g/dL (no blood transfusion or blood product administration within 14 days prior to testing).
• \*\*Liver:\*\* Serum total bilirubin (TBIL) ≤1.5 × upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN (if liver metastases are present, AST and ALT ≤5 × ULN are permitted).
• \*\*Kidneys:\*\* Serum creatinine ≤1.5 × ULN or creatinine clearance ≥60 mL/min, blood urea nitrogen ≤200 mg/L.
• Thyroid-stimulating hormone (TSH) ≤1 × ULN (if abnormal, free T3 \[FT3\] and free T4 \[FT4\] levels should also be assessed; if FT3 and FT4 levels are normal, the patient may be enrolled).
• Urine protein ≤1+; if urine protein \>1+, a 24-hour urine protein collection is required, and the total amount must be ≤1 gram.
• Normal cardiac function, defined as an electrocardiogram (ECG) without clinically significant abnormalities and a left ventricular ejection fraction (LVEF) \>50% as shown by echocardiography.
• Female subjects of childbearing potential must have a negative serum pregnancy test result prior to the first dose of the investigational drug.
• Male or female subjects of childbearing potential must use highly effective contraception methods (e.g., oral contraceptives, intrauterine devices, sexual abstinence, or barrier methods combined with spermicide) throughout the entire trial period and continue contraception for 90 days after the end of treatment.

You may not qualify if:

• Prior treatment with PD-1/PD-L1/PD-L2/CTLA-4 antibodies, or drugs targeting T-cell receptor activation or inhibition (e.g., OX40, CD137).
• Allergy to recombinant humanized anti-PD-1 monoclonal antibody or its components.
• Cutaneous melanoma, ocular melanoma, or melanoma of unknown primary origin.
• Primary lesion cannot be completely resected; presence of distant metastases; or local lesions are not indicated for surgery.
• Concurrently receiving any other anti-tumor therapy.
• Pregnancy, lactation, or women of childbearing potential not using contraception.
• Uncontrolled severe acute infection.
• Presence of any uncontrolled clinical condition, including but not limited to:
• Persistent or active (severe) infection;
• Poorly controlled diabetes;
• Cardiac disease (NYHA Class III/IV congestive heart failure or heart block);
• Current or suspected autoimmune disease, or history of autoimmune disease or syndromes requiring systemic steroid/immunosuppressant therapy, such as hypophysitis, colitis, hepatitis, nephritis, hyperthyroidism, hypothyroidism, etc.;
• Occurrence of any of the following within 6 months prior to the first dose: deep vein thrombosis or pulmonary embolism; myocardial infarction; severe or unstable arrhythmia or angina; percutaneous coronary intervention, acute coronary syndrome, or coronary artery bypass graft; cerebrovascular accident, transient ischemic attack, or cerebral embolism.
• Patients with active hepatitis B or C:
• If HBsAg or HBcAb is positive, HBV DNA must be tested (excluded if above the upper limit of normal).

Sponsors & Collaborators

• Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University: lead

Study Sites (1)

Shanghai Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200011, China

Location

MeSH Terms

Interventions

lenvatinib; Temozolomide

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Guoxin Ren M.D. the Ninth People's Hospital Affiliated to Shanghai Jiao Tong

CONTACT

13916948812; scjtdcq@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: SPONSOR

Study Record Dates

• First Submitted: January 13, 2026
• First Posted: January 20, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: January 20, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)