• Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of cutaneous melanoma (or unknown primary) will be enrolled in this study.

• Male participants: A male participant must agree to use a contraception during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.

• Female participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:

‣ Not a woman of childbearing potential (WOCBP); OR

⁃ A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment.

• Participants must have progressed on treatment with an anti-PD-1/L1 mAb administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies. PD-1 treatment progression is defined by meeting all of the following criteria:

‣ Has received at least 2 doses of an approved anti-PD-1/L1 mAb.

⁃ Participants who progressed on/within 3 months of adjuvant therapy with anti-PD-(L)1 inhibitor will be allowed.

⁃ Has demonstrated disease progression after anti-PD-1/L1 as defined by RECIST v1.1. The initial evidence of PD is to be confirmed by a second assessment no less than 4 weeks from the date of the first documented PD, in the absence of rapid clinical progression (as defined in 4.c).

⁃ Progressive disease has been documented within 12 weeks from the last dose of anti-PD-1/L1 mAb.

⁃ Progressive disease as determined above. This determination is made by the treating investigator. Once PD is confirmed, the initial date of PD documentation will be considered the date of PD. Anti-PD/L1 mAb need not be the most recent line of therapy administered.

• Prior treatment with an anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody is allowed but not required.

• Prior treatment with BRAF/MEK inhibitor therapy (if BRAF mutated) is allowed but not required.

• The participant provides written informed consent for the trial.

• Presence of measurable disease based on RECIST 1.1.

‣ Patients need to have at least one measurable lesion and a separate lesion for biopsy. Patients with only 1 lesion may be enrolled after discussion with Sponsor-Investigator.

⁃ Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.

• Able to provide newly obtained core or excisional biopsy of a tumor lesion not previously irradiated to undergo tumor biopsy (core, punch, incisional or excisional).

• \--- Biopsy must meet minimal sampling criteria.

• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed at screening prior to the first dose of study intervention.

• Have adequate organ function as defined below. Specimens must be collected within 28 days prior to the start of study intervention.

‣ Absolute neutrophil count (ANC) ≥1500/µL

⁃ Platelets ≥100 000/µL

⁃ Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L (Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks)

⁃ Creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN (Creatinine clearance (CrCl) should be calculated per institutional standard)

⁃ Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN

⁃ AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)

⁃ International normalized ratio (INR) OR prothrombin time (PT) and Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants