• Patients must have measurable disease as per RECIST v1.1 criteria and documented by CT and/or MRI

• Part 2 includes but is not limited to:

• Cutaneous melanoma that is either locally unresectable or metastatic:

‣ BRAF wild type: progressed after receiving PD-1 containing therapy with or without an anti-CTLA-4

⁃ BRAF mutation: patients who refused BRAF+MEK inhibitor

⁃ Must have objective progression after receiving at least two cycles of prior doublet therapy (anti-PD-1/anti-CTLA-4 or anti-PD-1/anti-LAG-3)

⁃ Radiographic progression ≥ 4 weeks prior to the first dose of study drug to rule out late response to most recent therapy. The requirement for documented radiologic progression may be waived after review by Medical Monitor (e.g., in the case of progression beyond 12 weeks after starting a doublet)

⁃ LDH ≤ 2.5 x ULN

• NSCLC: Unresectable locally advanced or metastatic PD-L1-positive (tumor proportion score \[TPS\] ≥ 1%) NSCLC not harboring an activating EGFR mutation or ALK rearrangement and has progressed during or following treatment with an anti-PDx with or without platinum-based chemotherapy

• Part 3: NSCLC as described above

• Part 4: cutaneous melanoma

‣ Unresectable locally advanced or metastatic cutaneous melanoma that has progressed during or following treatment with an anti-PDx (unless ineligible for anti-PDx therapy)

⁃ Patients with BRAF mutations must either be ineligible for or have refused a BRAF+MEK inhibitor

⁃ Must have objective progression after receiving at least two cycles of prior doublet therapy (anti-PD-1/anti-CTLA-4 or anti-PD-1/anti-LAG-3).

⁃ Radiographic progression ≥ 4 weeks prior to the first dose of study drug to rule out late response to most recent therapy. The requirement for documented radiologic progression may be waived after review by Medical Monitor (e.g., in the case of progression beyond 12 weeks after starting a doublet)

⁃ LDH ≤ 2.5 x ULN

• Female patients of childbearing potential must have a negative serum or urine pregnancy test performed within 72 hours prior to the initiation of study drug administration. Female patients of childbearing potential must be willing to use two forms of contraception throughout the study, starting with Screening through 60 days after the last dose of study drug (or 5 months after the last dose of study drug for patients receiving nivolumab). Abstinence is acceptable if this is the established and the preferred contraception method for the patient

• Male patients with partners of childbearing potential must use barrier contraception from the time of consent through 60 days after discontinuation of study drug and must not donate sperm during this period. In addition, male patients should have their partners use contraception (as documented for female patients) for the same period of time

• Patients who have previously received an immune checkpoint inhibitor (e.g., anti-PD-L1, anti-PD-1, anti-CTLA-4) prior to enrollment must have checkpoint inhibitor immune-related toxicity resolved to either Grade ≤ 1 or baseline (prior to the checkpoint inhibitor) to be eligible for enrollment. Patients who experienced previous checkpoint inhibitor-related hypothyroidism are eligible for the study regardless of grade resolution if well controlled on thyroid hormone replacement therapy

• Symptomatic central nervous system (CNS) metastases must have been treated, be asymptomatic for ≥ 14 days, and meet the following at the time of enrollment:

• No concurrent treatment for CNS disease (e.g., surgery, radiation, corticosteroids ≥ 10 mg prednisone/day or equivalent)

• No concurrent leptomeningeal disease or cord compression