A Study of QL1706 Combined With OH2 Injection in Perioperative Treatment of Stage III Resectable Acral Melanoma

Prior treatment

• Patients who have previously received treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 agents.
• 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.
• Use of an investigational drug within 4 weeks prior to randomization.
• Receipt of another anti-tumor monoclonal antibody (mAb) therapy within 4 weeks prior to randomization, or failure of adverse events from prior therapy (occurring more than 4 weeks earlier) to recover to ≤ Grade 1.
• Patients with known hypersensitivity to the investigational drug, its active ingredients, or excipients.
• Patients with active central nervous system (CNS) metastases. Patients with adequately treated CNS metastases whose neurological symptoms have recovered to ≤ Grade 1 (CTCAE criteria) for at least 2 weeks prior to randomization (excluding residual signs or symptoms related to CNS treatment) may participate in the study. In addition, patients must not be using corticosteroids, or must be on a stable dose of ≤10 mg prednisone/day (or equivalent), or must have tapered to ≤10 mg prednisone/day.
• Patients with autoimmune disease, history of liver or other organ transplantation, active tuberculosis; or patients who have undergone major surgery, live vaccination, or immunotherapy within 4 weeks prior to randomization.
• Patients who have received any other investigational product or participated in another interventional clinical trial within 30 days prior to the screening period.

Other illness

• Patients with a history of other malignancy (including unknown primary site) within 5 years prior to randomization. Note: Patients with curatively treated Stage 1 or 2 basal/squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ are excluded.
• Patients with any unstable systemic disease, including but not limited to: severe infection, uncontrolled diabetes, unstable angina, cerebrovascular accident or transient ischemic attack, myocardial infarction, congestive heart failure, severe arrhythmia requiring medication, liver, kidney, or metabolic disease.
• Patients with diseases (e.g., mental illness) or conditions (e.g., alcoholism or drug abuse) that may increase the risk of study drug administration, affect study compliance, or interfere with the interpretation of study results.
• Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study; male or female patients unwilling to use effective contraception. Other conditions deemed unsuitable for enrollment by the investigator.

Lab values

• Patients who are positive for hepatitis B surface antigen (HBsAg) with a hepatitis B virus DNA copy number \>1×10³ copies/mL; patients who test positive for hepatitis C virus (HCV) antibody or human immunodeficiency virus (HIV) antibody.

Other

• Patients whose lesions do not meet the volume requirements for intratumoral injection or are unsuitable for intratumoral injection.
• Lesions that cannot accommodate an intratumoral injection volume of 1 mL.
• Tumor invasion of major blood vessels such as iliac or femoral vessels.

• Voluntarily sign the written informed consent form.
• 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.
• Expected survival ≥4 months.
• Adequate organ function: a) Hematology (without any blood component or growth factor support within 7 days before the start of study treatment): i. Absolute neutrophil count (ANC) ≥1.5×10⁹/L (1,500/mm³); ii. White blood cell count ≥3.0×10⁹/L; iii. Platelet count \>100×10⁹/L (100,000/mm³); iv. Hemoglobin ≥90 g/L. b) Renal: i. Serum creatinine ≤1.5×ULN, or 24-hour creatinine clearance ≥50 mL/min (calculated according to the Cockcroft-Gault formula); ii. Urine protein \<2+ or 24-hour urine protein quantification \<1.0 g. c) Hepatic: i. Serum total bilirubin (TBil) ≤1.5×ULN; ii. AST and ALT ≤2.5×ULN; iii. Serum albumin (ALB) ≥28 g/L. d) Coagulation: i. International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤1.5×ULN (if the subject is receiving anticoagulant therapy, the subject must be on a stable dose of anticoagulant, and the coagulation parameters \[PT/INR and APTT\] at screening should be within the expected therapeutic range for the anticoagulant used). e) Cardiac function: i. Left ventricular ejection fraction (LVEF) ≥50%.
  • 6、Female patients of childbearing potential (including those with premature menopause, menopause \<2 years, and those who have not undergone surgical sterilization), male patients, and their partners must agree to use effective contraception during the study period, including surgical sterilization, oral contraceptives, intrauterine devices, abstinence, or barrier contraception combined with spermicide. All patients must continue contraception for 6 months after the last treatment.
  • 8、Subjects with a history of genital herpes must have a 3-month interval after the herpes has resolved.
  • 9、Subjects must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study requirements.