This is a prospective, multicenter, open-label, 1:1 randomized phase II trial enrolling 76 patients with AJCC stage III surgically resectable acral melanoma. Arm A receives neoadjuvant combination of intratumoral OH2 oncolytic HSV2 plus IV QL1706 (Iparomlimab and Tuvonralimab Injection) for 6 q2w cycles before radical surgery, followed by stratified QL1706 adjuvant therapy. Arm B undergoes upfront radical surgery followed by single-agent QL1706 adjuvant therapy for up to 1 year. The primary endpoint is 2-year EFS rate. Secondary endpoints include pathologic response, RFS, OS, and overall safety profile. All patients receive regular imaging follow-up up to 5 years post-surgery.
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Male or female patients aged ≥18 years and ≤75 years at the time of enrollment.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Histologically and/or cytologically confirmed resectable Stage III acral melanoma (according to the AJCC 8th edition staging system for cutaneous malignant melanoma) with at least one measurable lesion.
Patients who have previously received treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 agents.
Patients whose lesions do not meet the volume requirements for intratumoral injection or are unsuitable for intratumoral injection.
Patients who have received anti-herpes simplex virus therapy (e.g., acyclovir, ganciclovir, valacyclovir, vidarabine) within 4 weeks prior to randomization, except for patients with hepatitis B who are receiving ongoing treatment with entecavir, tenofovir disoproxil fumarate, or adefovir dipivoxil.
Receipt of a live attenuated vaccine within 4 weeks prior to randomization.
Parallel
Iparomlimab and Tuvonralimab Injection (QL1706)
DrugA PD-1/CTLA-4 combination antibody produced using MabPair® technology. It contains two engineered monoclonal antibodies (anti-PD-1 IgG4 and anti-CTLA-4 IgG1) expressed at a fixed ratio from a single cell line. Administered intravenously. In the neoadjuvant phase: 3 mg/kg Q2W for 6 cycles. In the adjuvant phase: 5 mg/kg Q3W for up to 1 year. Manufactured by Qilu Pharmaceutical Co., Ltd. Supplied as 50 mg/2 mL vial. Store at 2-8°C, protect from light, do not freeze.
OH2 Injection(Recombinant Human GM-CSF Oncolytic Type II Herpes Simplex Virus)
DrugA genetically modified oncolytic type II herpes simplex virus (HSV2) strain HG52, with ICP34.5 and ICP47 genes deleted to enable selective replication in tumor cells and enhance antitumor immunity, and engineered to express human GM-CSF. Administered via intratumoral injection. Planned dose: 10\^7 CCID50/mL, Q2W for up to 6 cycles. Maximum single-visit volume: 8 mL, adjusted based on lesion diameter. Dose may be reduced to 10\^6 CCID50/mL in case of ≥ Grade 3 related AEs. Manufactured by Wuhan Binhui Bio-technology Co., Ltd. Supplied as 1 mL/vial. Store at -70°C or below.
2-Year Event-Free Survival Rate
Event-free survival (EFS) is defined as the time from randomization to the occurrence of any of the following events: disease progression leading to inoperability (development of locally unresectable disease or distant metastasis), local or distant recurrence, melanoma-related or treatment-related death. The occurrence of a new primary melanoma during treatment or follow-up will also be considered an event.
Pathologic Response Rate (pCR, Near pCR, pPR)
Assessment is performed according to the International Neoadjuvant Melanoma Consortium (INMC) scoring system. Partial pathological response (pPR) is defined as viable tumor cells ≥10% and ≤50%. Near pathological complete response (near pCR) is defined as viable tumor cells \>0% and \<10%. Pathological complete response (pCR) is defined as the absence of viable tumor cells. The aim is to evaluate pathological response rates, including the partial pathological response rate, major pathological response/near pathological complete response rate, and pathological complete response rate.
Relapse-Free Survival (RFS)
The time from randomization to the first occurrence of any of the following events: disease recurrence (local, regional, or distant metastasis) or death from any cause, whichever occurs first.
Overall Survival (OS)
The time from randomization to death from any cause.
The incidence and severity of adverse events (AEs)
Safety
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Peking University Cancer Hospital & Institute
Lead sponsor
Qilu Pharmaceutical Co., Ltd.
Collaborator
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