NeoLIPA: Neoadjuvant LTX-315 in Combination with Pembrolizumab in Resectable Stage III/IV Melanoma

Inclusion Criteria: * Participant must be 18 years of age inclusive, at the time of signing the informed consent. * Histologically confirmed, clinically detectable stage III-IV(M1a) melanoma, judged fully resectable and eligible for neoadjuvant treatment by consensus at a multidisciplinary tumor board. Patients with melanoma of cutaneous (including acral) or mucosal (including conjunctival) origin are eligible. Clinically detectable is defined as being apparent and measurable by radiological assessments or physical examination. * Measurable disease as per RECIST version 1.1 criteria. * Judged medically fit to undergo the planned surgery by the surgical team. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Have at least one superficial cutaneous, subcutaneous or lymph node lesion available for injection with a maximum mean longest perpendicular diameter (LPD) of 3.0 cm. * Willing to undergo an additional tumor biopsy and submit biopsy and surgical specimens * Adequate organ function as defined below: 1. Hemoglobin \> 9 g/dL 2. Absolute neutrophil count (ANC) ≥ 1.0 x 109/L 3. Platelet count ≥ 80 x 109/L e. Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) f. AST and ALT ≤2.5 x ULN g. Albumin \>30 g/L h. Serum creatinine ≤1.5 X ULN OR measured creatinine clearance (CL) \>30 mL/min * Female participants are willing to use contraceptive measures as prescribed by the protocol from study visit 1 to 120 days after the last dose of study intervention. Women of childbearing potential must have a negative urine or serum pregnancy test within 72 hours of first study intervention. * Capable of giving signed informed consent as described in section 10.1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Exclusion Criteria: * Uveal melanoma. Patients with acral, mucosal or conjunctival melanoma are eligible. * History of brain, bone, liver metastases or leptomeningeal metastases. * Patients with stage IV disease having ≥4 metastatic sites. * A history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator. * Active autoimmune disease requiring systemic immunomodulatory treatment. Replacement therapy (e.g. physiologic doses of corticosteroids, insulin, thyroxine) is allowed. * Patient has history of, or any evidence of interstitial lung disease (ILD) or non-infectious pneumonitis that required systemic corticosteroids. * Prior malignancy that require concurrent therapy. * Allergy/hypersensitivity to prophylactic treatments; known hypersensitivity to pembrolizumab or LTX-315 or any of their excipients * Previous treatment with anti-cancer immunotherapy, including (but not limited to) CTLA-4 or PD-1 inhibitors. Prior non-immunotherapy adjuvant treatment (e.g. dabrafenib + trametinib or radiotherapy), and regional therapy such as ECT or ILP is permitted (≥ 12 weeks prior to enrollment). * Currently taking immunosuppressive agents or use of systemic corticosteroids (≥10 mg of prednisolone or equivalent) or other systemic immunosuppressive drugs within 28 days prior to study drug administration. Topical and inhaled corticosteroids are allowed. * Have received a live vaccine within 30 days prior to first dose of treatment * Have received an investigational drug within 4 weeks to day 1, or are scheduled to receive one during the treatment period. * Pregnant or breastfeeding. * Any reason why, in the opinion of the investigator, the patient should not participate.