Mirdametinib + BGB-3245 in Advanced Solid Tumors

Key Inclusion Criteria: * Able to provide informed consent * At least 18 years of age on day of signing ICF * Advanced, metastatic or unresectable solid cancer that has not responded to or progressed during or after at least 1 line of appropriate therapy or for which there is no treatment available or prior therapy was not tolerated. * Part 1: oncogenic mutation or other genomic aberration of the MAPK pathway * Part 2: oncogenic mutation or genomic aberration defined below: * Cohort A: cutaneous melanoma harboring NRAS mutations. * Cohort B: non-small cell lung cancer (NSCLC) harboring a KRAS mutation. * Cohort C: NSCLC or cutaneous melanoma harboring BRAF Class II or Class III mutations or BRAF Fusion mutation. * Must have archival tumor tissue or agree to a fresh tumor biopsy at screening * Measurable disease per RECIST 1.1 * Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 * Adequate organ function and no transfusion within 14 days of first dose Key Exclusion Criteria: * Central Nervous System metastases, leptomeningeal carcinomatosis or untreated spinal cord compression * History of glaucoma * Active parathyroid disorder or history of malignancy associated hypercalcemia * Clinically significant cardiac disease within the past 6 months of signing ICF * History of toxicity from another RAF, MEK, ERK inhibitor requiring discontinuation of treatment from these agents * Severe or uncontrolled systemic disease * Inability to swallow oral medications * Clinically significant active infection (HIV, Hepatitis B or Hepatitis C) * History of or ongoing Immune Thrombocytopenia (ITP), Von Willebrand disease and/or other past or present bleeding disorders * Underlying medical conditions in investigator's opinion to be unfavorable to be a part of the study * Major surgical procedure or significant traumatic injury within 4 weeks prior to first dose or anticipates need for major surgery while on study * Systemic anti-cancer therapy within 2 weeks or 5 half-lives before first dose * Concomitant systemic or glucocorticoid therapy within 2 weeks before first dose * Concomitant medicines that are strong CYP3A4 inhibitors or inducers within 2 weeks or 5 half-lives before first dose * Live vaccine within 4 weeks before first dose