Neoadjuvant Pucotenlimab Combined With Lenvatinib and Temozolomide in Resectable Stage IIB/III Acral Melanoma

NCT07501104 | Not Yet Recruiting Phase 2

• 1 other identifier: B2026-007R
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a single-arm, open-label, single-center, Phase II exploratory clinical study evaluating the efficacy, safety, and tolerability of neoadjuvant pucotenlimab combined with lenvatinib and temozolomide in patients with resectable Stage IIB/III acral melanoma. After providing written informed consent, eligible subjects will receive neoadjuvant combination therapy consisting of pucotenlimab, lenvatinib, and temozolomide, with each treatment cycle lasting 3 weeks. Surgical resection will be performed after 3 cycles of treatment. Postoperative adjuvant therapy will be determined based on the pathological results of the surgical specimens. Subjects who do not achieve a major pathological response (MPR) will receive pucotenlimab maintenance therapy for a total of 1 year, while subjects who achieve an MPR will be exempt from adjuvant therapy. Treatment will continue until the completion of adjuvant therapy, disease progression, unacceptable toxicity, initiation of a new anti-tumor therapy, withdrawal of informed consent, loss to follow-up, death, or discontinuation determined by the investigator, whichever occurs first.

Conditions

Melanoma (Skin Cancer)

Outcome Measures

Primary Outcomes (1)

• Major Pathological Response (MPR) Rate

  Up to the time of surgery (assessed approximately 9-10 weeks after the start of neoadjuvant therapy)

Secondary Outcomes (1)

• Pathological Complete Response (pCR) Rate

  Up to the time of surgery (assessed approximately 9 weeks after the start of treatment)

Study Arms (1)

Neoadjuvant Pucotenlimab+Lenvatinib+Temozolomide

EXPERIMENTAL

Drug: Neoadjuvant Pucotenlimab+Lenvatinib+Temozolomide

Interventions

Neoadjuvant Pucotenlimab+Lenvatinib+Temozolomide DRUG

Pucotenlimab: Administered via intravenous (IV) infusion at a dose of 200 mg on Day 1 of each 21-day cycle. Temozolomide: Administered orally at a dose of 200 mg/m\^2 once daily on Days 1 to 5 of each 21-day cycle. Lenvatinib: Administered orally once daily at a dose of 8 mg for patients weighing \< 60 kg, or 12 mg for patients weighing ≥ 60 kg.

Neoadjuvant Pucotenlimab+Lenvatinib+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:

• Fully understand the study and voluntarily sign the informed consent form (ICF). (Note: Items 1 and 10 are similar, but both are translated here) Age ≥ 18 and ≤ 75 years old. Histologically or cytologically confirmed resectable Stage IIB-III melanoma. Have at least one measurable lesion according to RECIST 1.1 criteria. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1.
• Life expectancy of ≥ 6 months. No prior systemic drug therapy for melanoma.
• Adequate major organ function meeting the following criteria:
• Hematology (without blood transfusion or use of hematopoietic stimulating factors within 14 days): Hemoglobin (Hb) ≥ 90 g/L; Absolute Neutrophil Count (ANC) ≥ 1.5×10\^9/L; Platelets (PLT) ≥ 100×10\^9/L; White Blood Cell (WBC) count ≥ 3.0×10\^9/L.
• Biochemistry: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN (upper limit of normal) (for patients with liver metastasis, ≤ 5 × ULN); Serum total bilirubin (TBIL) ≤ 1.5 × ULN (for patients with Gilbert's syndrome, ≤ 3 × ULN); Serum creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance rate ≥ 50 ml/min.
• Coagulation: Activated partial thromboplastin time (APTT), International Normalized Ratio (INR), and Prothrombin Time (PT) ≤ 1.5 × ULN.
• Doppler ultrasound assessment: Left ventricular ejection fraction (LVEF) ≥ 50%. Women of childbearing potential must agree to use acceptable methods of contraception (e.g., intrauterine device \[IUD\], oral contraceptives, or condoms) during the study and for 6 months after the end of the study; must have a negative serum pregnancy test within 7 days prior to study enrollment, and must not be breastfeeding. Male patients must agree to use acceptable methods of contraception during the study and for 6 months after the end of the study.
• Agree to and sign the study Informed Consent Form (ICF) before initiating any study-related procedures.

You may not qualify if:

• Prior treatment with immune checkpoint inhibitors (including but not limited to pembrolizumab, nivolumab) or lenvatinib.
• Received anti-cancer therapy within 28 days (or 5 times the half-life, whichever is shorter) prior to the first dose of study treatment, or received any investigational drug therapy within 30 days.
• Underwent major surgery, open biopsy, or experienced major trauma within 4 weeks prior to enrollment.
• Use of immunosuppressive medications within 14 days prior to the start of treatment, excluding intranasal and inhaled corticosteroids or physiological doses of systemic corticosteroids (i.e., daily dose of prednisolone ≤ 10 mg or equivalent physiological doses of other corticosteroids).
• Any active autoimmune disease or a history of autoimmune disease (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism; except for subjects with vitiligo or asthma that completely resolved in childhood and currently do not require medical intervention, or a history of allogeneic organ transplant or allogeneic hematopoietic stem cell transplant).
• INR \> 1.5 or APTT \> 1.5 × ULN. Currently poorly controlled hypertension, defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg.
• Subjects with proteinuria \> 1+ on urinalysis will undergo a 24-hour urine collection to quantitatively assess proteinuria; those with urine protein ≥ 1 g/24 hours will be ineligible.
• Any current disease or condition that affects drug absorption, or inability to take lenvatinib orally.
• Current digestive tract diseases such as active gastric/duodenal ulcers or ulcerative colitis, active bleeding from an unresected tumor, or other conditions judged by the investigator as likely to cause gastrointestinal bleeding or perforation.
• Evidence or history of significant bleeding tendency within 3 months prior to enrollment (bleeding \> 30 mL within 3 months, hematemesis, melena, hematochezia), hemoptysis (\> 5 mL of fresh blood within 4 weeks), or occurrence of thromboembolic events (including stroke and/or transient ischemic attack) within 12 months.
• Clinically significant cardiovascular disease, including but not limited to acute myocardial infarction, severe/unstable angina, or coronary artery bypass grafting within 6 months prior to enrollment; New York Heart Association (NYHA) Class \> 2 congestive heart failure; ventricular arrhythmias requiring medical treatment; LVEF \< 50%.
• History of other malignancies within the past 5 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.
• Active or poorly controlled severe infections (≥ CTCAE v5.0 Grade 2 infection). Known human immunodeficiency virus (HIV) infection; known history of clinically significant liver disease, including viral hepatitis \[known hepatitis B virus (HBV) carriers must rule out active HBV infection, i.e., HBV DNA positive (\> 1×10\^4 copies/mL or \> 2000 IU/mL); known hepatitis C virus (HCV) infection with positive HCV RNA (\> 1×10\^3 copies/mL), or other hepatitis, cirrhosis\] (excluding patients whose relevant test results returned to normal after prior antiviral treatment).
• Unstable or clinically symptomatic brain metastases. Persistent toxicities from any prior anti-tumor therapies that have not recovered to ≤ CTCAE v5.0 Grade 2, though patients with any grade of alopecia are permitted to participate.
• Pregnant (positive pregnancy test prior to administration) or breastfeeding women.

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Wei

CONTACT

+86 13681973586; wei.chuanyuan@zs-hospital.sh.cn

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: March 24, 2026
• First Posted: March 30, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2029
• Last Updated: March 30, 2026

Record last verified: 2026-03