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

NCT06804824
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Phase
Phase 1
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Recruitment status
Recruiting
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Participants
220
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Lead sponsor
Vividion Therapeutics, Inc.
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Start date
2025-02-25
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Number of sites
9
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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.
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Short title
A First-in-Human (FIH) Study to Evaluate the Safety and Tolerability of VVD-159642 in Participants With Advanced Solid Tumors
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Official 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
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1
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Study type
Interventional
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Completion date
2027-08-01
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First posted
2025-02-03
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Registry last updated
2026-03-18
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Primary completion date
2027-08-01
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Start date
2025-02-25
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Participants
220
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Participant count basis
Estimated
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Planned participants
220
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Protocol amendments
2
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Number of sites
9
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
Vividion Therapeutics, Inc.
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06804824
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ClinicalTrials.gov ID
NCT06804824
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Registry record
Open registry record
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Allocation
Not randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

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

    Timeframe: 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)

    Timeframe: Up to approximately 29 months

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

    Timeframe: Up to approximately 29 months

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

    Timeframe: Up to approximately 29 months

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

    Timeframe: 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

    Timeframe: 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)

    Timeframe: 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)

    Timeframe: 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)

    Timeframe: 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)

    Timeframe: 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

    Timeframe: 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

    Timeframe: 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

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

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy 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).
Sources for eligibility
clinicaltrials.gov

  • START Mid WestGrand Rapids, United StatesRecruiting
  • NEXT AustinAustin, United StatesRecruiting
  • NEXT DallasIrving, United StatesRecruiting
  • START San AntonioSan Antonio, United StatesRecruiting
  • NEXT San AntonioSan Antonio, United StatesRecruiting
  • START MountainOgden, United StatesRecruiting
  • NEXT VirginiaFairfax, United StatesRecruiting
  • Clinical Research South Australia (CRSA)Adelaide, AustraliaRecruiting
  • Linear ClinicalNedlands, AustraliaRecruiting
Sources for sites
clinicaltrials.gov

Related records

Drugs (2)

Lead sponsors (1)

Targets (3)