CLINICAL TRIAL / NCT05585320

Inclusion Criteria: - Must be ≥18 years of age - Must have histologically or cytologically confirmed diagnosis as follows: 1. Monotherapy Phase 1: A locally advanced unresectable or metastatic solid tumor malignancy that harbors a RAS (KRAS, NRAS, or HRAS) activating mutation. 2. Monotherapy Phase 2a: A locally advanced unresectable or metastatic solid tumor malignancies: pancreatic ductal adenocarcinoma (PDAC), RAS-mutant melanoma, or RAS-mutant non-small cell lung cancer (NSCLC) 3. Combination therapy (both phases): A locally advanced unresectable or metastatic PDAC 4. Combination therapy Phase 2a, Treatment D: Second and third line participants with unresectable stage III or stage IV cutaneous melanoma with BRAF mutation. Must have progressed on or after treatment with an anti-PD-(L)1 monoclonal antibody as the most recent therapy. First day of study treatment must be more than 28 days but less than 12 weeks from the last dose of anti-PD-(L)1 mAb. 5. Combination therapy Phase 2a, Treatment E: Second and third line participants with unresectable stage III or stage IV cutaneous melanoma. Must have progressed on or after treatment with an anti-PD-(L)1 monoclonal antibody as the most recent therapy. First day of study treatment must be more than 28 days but less than 12 weeks from the last dose of anti-PD-(L)1 mAb. - Participants must be treatment naive or received prior systemic standard-of-care treatment as follows: 1. Monotherapy Phase 1: received at least 1 line of systemic standard-of-care treatment for their advanced or metastatic disease 2. Monotherapy Phase 2a: 1. First-line PDAC participants will have received no previous systemic anti-cancer therapy. Second-line PDAC participants will have received no more than one prior systemic anti-cancer therapy. 2. First-line melanoma participants will have received no previous systemic anti-cancer therapy. Second- and third-line participants will have received and failed one or two prior systemic anti-cancer therapies, respectively. 3. NSCLC participants will have received at least one and no more than two previous lines of systemic therapy. 3. Combination therapy (both phases): PDAC participants will have received no previous systemic anti-cancer therapy for their advanced or metastatic disease. - Must have evidence of measurable disease (at least one target lesion) per RECIST v1.1 criteria - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Adequate organ function Exclusion Criteria: - Inability to swallow oral medications - Symptomatic, untreated, or actively progressing known central nervous system (CNS) metastases - History or concurrent evidence of retinal vein occlusion (RVO) or current risk factors for RVO. History of serous retinopathy, retinal edema, or retinal pigment epithelial detachment (RPED) - Impaired cardiovascular function or clinically significant cardiac disease - History of rhabdomyolysis within 3 months prior to start of study treatment - Active skin disorder requiring systemic treatment within 3 months prior to the start of study treatment - Participants with active, uncontrolled autoimmune disease or participants actively being treated with tumor necrosis factor-alpha (TNF-alpha) inhibitors for management of their autoimmune disease are excluded - Receipt of an allogeneic tissue/solid organ transplant - Females who are pregnant, breastfeeding, or planning to become pregnant and males who plan to father a child while enrolled in this study.