A First-in-Human (FIH) Study to Evaluate the Safety and Tolerability of VVD-159642 in Participants With Advanced Solid Tumors

A FIH study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor activity of VVD-159642, a rat sarcoma viral oncogene-phosphatidylinositol 3-kinase alpha (RAS-PI3Kα) inhibitor, as a single agent and in combination with either sotorasib or trametinib in participants with advanced solid tumors.

Key Inclusion Criteria: * For Part 1 Dose Escalation, the prospective participant must have histologically confirmed pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC), non-small cell lung cancer (NSCLC), or any solid tumor that harbors a rat sarcoma viral oncogene (RAS) alteration \[Kirsten rat sarcoma viral oncogene homolog (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), Harvey rat sarcoma viral oncogene homolog (HRAS)\] as per local /historical testing; any solid tumor that harbors an epidermal growth factor receptor (EGFR) alteration as per local/historical testing; or human epidermal growth factor receptor 2 (HER2) overexpression (immunohistochemistry \[IHC\] 3+ or IHC 2+/fluorescence in situ hybridization \[FISH\] positive) as per local/historical testing. * Have histologically or cytologically confirmed metastatic or unresectable solid tumors. * Measurable disease by RECIST version 1.1 as assessed by the investigator. * Eastern Cooperative Oncology Group (ECOG) performance status ≤1. * Adequate bone marrow, kidney, and liver function as defined in the protocol. * Able to take oral medications. Key Exclusion Criteria: * Active central nervous system (CNS) malignancies. * History of cardiac diseases as defined in detail in the protocol. * Uncontrolled arterial hypertension despite optimal medical management (per investigator's opinion). * History of inflammatory bowel disease or any malabsorption syndrome or any conditions that would interfere with enteral absorption and/or may interfere with the conduct of the study. * Active hepatitis B infection \[positive for hepatitis B surface antigen and Hepatitis B virus deoxyribonucleic acid (DNA)\]. * Active hepatitis C infection (positive anti-hepatitis C virus \[HCV\] antibody and quantitative HCV ribonucleic acid (RNA) results greater than the lower limits of detection of the assay).