Cancerify Logo
Log inSign up
Back to clinical trials
RecruitingInterventionalPhase 1

A Phase 1/1b, Open-Label, Multicenter, First-in-Human Dose Escalation and Dose Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Anti-Tumor Activity of VVD-159642, a RAS-PI3Kα Inhibitor, as a Single Agent and in Combination in Participants With Advanced Solid Tumors

NCT ID: NCT06804824Sponsor: Vividion Therapeutics, Inc.Last updated: 2026-03-18

Summary

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.

Arms & interventions

  • DrugVVD-159642

    Oral capsules

  • DrugSotorasib

    Oral tablets

  • DrugTrametinib

    Oral tablets

Outcome measures

Primary

  • Part 1: Incidence and Severity of Dose-limiting Toxicities (DLTs)

    Time frame: From Day 1 to Day 21 of Cycle 1 [cycle length=21 days]

  • Part 2: Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Time frame: Up to approximately 29 months

  • Part 2: Incidence and Severity of Clinically Significant Changes in Vital Signs

    Time frame: Up to approximately 29 months

  • Part 2: Incidence and Severity of Clinically Significant Changes in Laboratory Evaluations

    Time frame: Up to approximately 29 months

Secondary

  • Part 1: Recommended Dose for Expansion (RDE) of VVD-159642 as a Single Agent

    Time frame: Up to approximately 29 months

  • Part 2: Recommended Phase 2 Dose (RP2D) of VVD-159642 as a Single Agent and in Combination with Sotorasib and Trametinib

    Time frame: Up to approximately 29 months

  • Part 2: Overall Response Rate (ORR)

    Time frame: Up to approximately 29 months

  • Part 2: Duration of Response (DoR)

    Time frame: Up to approximately 29 months

  • Part 2: Progression-free Survival (PFS)

    Time frame: Up to approximately 29 months

  • Part 2: Disease Control Rate (DCR)

    Time frame: Up to approximately 29 months

  • Parts 1 and 2: Area Under the Plasma Concentration-time Curve (AUC) of VVD-159642 as a Single Agent and in Combination With Sotorasib and Trametinib

    Time frame: Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days)

  • Parts 1 and 2: Maximum Plasma Concentration (Cmax) of VVD-159642 as a Single Agent and in Combination With Sotorasib and Trametinib

    Time frame: Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days)

  • Parts 1 and 2: Half-life (t1/2) of VVD-159642 as a Single Agent and in Combination With Sotorasib and Trametinib

    Time frame: Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days)

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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).

Study locations (7)

START Mid West

Grand Rapids, Michigan, 49546

Recruiting

NEXT Austin

Austin, Texas, 78758

Recruiting

NEXT Dallas

Irving, Texas, 75039

Recruiting

START San Antonio

San Antonio, Texas, 78229

Recruiting

NEXT San Antonio

San Antonio, Texas, 78299

Recruiting

START Mountain

Ogden, Utah, 84401

Recruiting

NEXT Virginia

Fairfax, Virginia, 22031

Recruiting