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.
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.
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.
Sequential
VVD-159642
DrugOral capsules
Sotorasib
DrugOral tablets
Trametinib
DrugOral tablets
Part 1: Incidence and Severity of Dose-limiting Toxicities (DLTs)
Part 2: Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Part 2: Incidence and Severity of Clinically Significant Changes in Vital Signs
Part 2: Incidence and Severity of Clinically Significant Changes in Laboratory Evaluations
Part 1: Recommended Dose for Expansion (RDE) of VVD-159642 as a Single Agent
The RDE will be based on safety, tolerability, PK, and preliminary anti-tumor activity of VVD-159642 as a single agent during the dose escalation phase.
Part 2: Recommended Phase 2 Dose (RP2D) of VVD-159642 as a Single Agent and in Combination with Sotorasib and Trametinib
The RP2D will be based on safety, tolerability, PK and preliminary anti-tumor activity of VVD-159642 as single agent, and in combination with sotorasib and trametinib during Part 2.
Part 2: Overall Response Rate (ORR)
ORR is defined as the percentage of participants achieving a best overall response of complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator assessment.
Part 2: Duration of Response (DoR)
DOR is defined as the time from initial response of CR or PR to progressive disease or death, whichever comes first per RECIST version 1.1 by investigator assessment.
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