A Study of APG-115 in as a Monotherapy or Combination With Pembrolizumab in Patients With Metastatic Melanomas or Advanced Solid Tumors

Inclusion Criteria: * Male or non-pregnant, non-lactating female patients age ≥18 years, an exception for MPNST cohort: adolescents ≥12 years old (who weigh at least 40 kg) is allowed * Part 2: 1. Measurable disease according to RECIST 1.1. Lesions situated in a previously irradiated area, or an area subject to other loco-regional therapy (e.g., intralesional injections) should be considered non-measurable 2. ECOG performance status 0-2 3. Cohort A: Histologically confirmed, unresectable or metastatic melanoma, and refractory or relapse after PD-1 antibody treatment and ineligible for other standard of care therapy per NCCN guideline (previous PD-1/PD-L1 antibody treatment not required for uveal melanoma) 4. Cohort F: Histologically confirmed, metastatic or unresectable MPNST * Life expectancy ≥ 3 months * Continuance of treatment related toxicities (except alopecia) due to prior radiotherapy or chemotherapy agents or biological therapy (including PD-1/PD-L1 antibodies) must be ≤ grade 1 at the time of dosing * Adequate bone marrow and organ function without continuous supportive treatment * QTcF interval (mean of 3, 1-3 minutes between tests) ≤450 ms in males and ≤470 ms in females * Left ventricular ejection fraction (LVEF) ≥ lower limit of institutional normal (LLN) as assessed by echocardiogram (ECHO) or multigated acquisition (MUGA) scan * Tumor tissue must be provided for all subjects for biomarker analysis before treatment with investigational product * Willingness to use contraception by a method that is deemed effective by both male and female patients of childbearing potential and their partners throughout the treatment period and for at least three months following the last dose of study drug * Ability to understand and willingness to sign a written informed consent form. Exclusion Criteria: * Any prior systemic MDM2-p53 inhibitor treatment * Received chemotherapy within 21 days (42 days for nitrosoureas or mitomycin C) prior to first dose * Part 2 Cohort A: Prior loco-regional treatment with intralesional therapy (e.g., talimogene laherparepvec) for unresectable or metastatic melanoma in the last 6 weeks prior to start of study treatment * Part 2 Cohort B: Has received radiation therapy to the lung that is \>30Gy within 6 months of the first dose of trial treatment * Part 2 Cohort E: Known FGFR translocation mutation * Received hormonal and biologic, small molecule targeted therapies or other anti-cancer therapy within 21 days prior to first dose * Radiation or surgery within 14 days prior to first dose, thoracic radiation within 28 days prior to first dose * Has known active central nervous (CNS) metastases and/or carcinomatous meningitis. Or has neurologic instability per clinical evaluation due to tumor involvement of the CNS. * Requirement for corticosteroid treatment (with the exception of megestrol and local use of steroid: i.e., topical corticosteroids, inhaled corticosteroids for reactive airway disease, ophthalmic, intraarticular, and intranasal steroids * Concurrent treatment with an investigational agent or device within 21 days prior to the first dose of therapy * Failure to recover adequately, as judged by the investigator, from prior surgical procedures. Patients with active wound healing, patients who have had major surgery within 28 days from 1st dose of study treatment, and patients who have had minor surgery within 14 days from 1st dose of study treatment. * Unstable angina, myocardial infarction, or a coronary revascularization procedure within 180 days of study entry * Active rheumatoid arthritis (RA), active inflammatory bowel disease, chronic infections, or any other disease or condition associated with chronic inflammation * Active infection requiring systemic antibiotic/ antifungal medication, and known clinically active viral infection such as hepatitis B or C, HIV infection, or active COVID-19 * Has received a live vaccine within 30 days prior to first dose. * Has had an allogeneic tissue/solid organ transplant, prior stem cell or bone marrow transplant * Has previously had a severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb) * Any other condition or circumstance that would, in the opinion of the investigator, make the patient unsuitable for participation in the study * History of organ transplant requiring use of immunosuppressive medication * A woman of childbearing potential who has a positive urine or serum pregnancy test (within 72 hours) prior to treatment.