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NCT Number: NCT06804824

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.

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Key information

Conditions

Advanced Solid Tumors

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Clinical Research South Australia (CRSA), Adelaide, South Australia, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

VVD-159642

Drug

Oral capsules

Sotorasib

Drug

Oral tablets

Trametinib

Drug

Oral tablets

Primary outcomes

  1. 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]

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

    Time frame: Up to approximately 29 months

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

    Time frame: Up to approximately 29 months

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

    Time frame: Up to approximately 29 months

Secondary outcomes

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

    Time frame: Up to approximately 29 months

    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.

  2. 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

    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.

  3. Part 2: Overall Response Rate (ORR)

    Time frame: Up to approximately 29 months

    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.

  4. Part 2: Duration of Response (DoR)

    Time frame: Up to approximately 29 months

    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.

  5. Part 2: Progression-free Survival (PFS)

    Time frame: Up to approximately 29 months

    PFS is defined as the time from the date of randomization to the time of confirmed disease progression or death, whichever occurs first per RECIST version 1.1 by investigator assessment.

  6. Part 2: Disease Control Rate (DCR)

    Time frame: Up to approximately 29 months

    DCR is defined as the percentage of participants achieving CR or PR, or stable disease (SD) per RECIST version 1.1 by investigator assessment.

  7. 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)

  8. 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)

  9. 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)

Study contacts

Contact information is provided by the study sponsor or research team.

Vividion Clinical Trial Call Center

CONTACT

[email protected]

858-345-9752

Sponsors and collaborators

Lead sponsor

Vividion Therapeutics, Inc.

Industry

Registry information

Official study title

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

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Feb 3, 2025
Registry last updated
Mar 18, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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