A First-in-Human (FIH) Study to Evaluate the Safety and Tolerability of VVD-159642 in Participants With Advanced Solid Tumors
- Conditions
- Advanced Solid Tumors
- Interventions
- Registration Number
- NCT06804824
- Lead Sponsor
- Vividion Therapeutics, Inc.
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 220
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1: Dose Escalation: VVD-159642 Single Agent VVD-159642 Participants will receive ascending doses of VVD-159642, orally, daily in 21-day treatment cycles during Part 1. Part 2: Dose Expansion (Cohort A): VVD-159642 Single Agent VVD-159642 Participants will receive VVD-159642 at the recommended dose for expansion (RDE), orally, daily in 21-day treatment cycles during Part 2. Part 2: Dose Expansion (Cohort B): VVD-159642 + Sotorasib Sotorasib Participants will receive VVD-159642 at RDE orally, daily in combination with sotorasib, in 21-day treatment cycles after a safety run-in. Part 2: Dose Expansion (Cohort C): VVD-159642 + Trametinib VVD-159642 Participants will receive VVD-159642 at RDE orally, daily in combination with trametinib, in 21-day treatment cycles after a safety run-in. Part 2: Dose Expansion (Cohort C): VVD-159642 + Trametinib Trametinib Participants will receive VVD-159642 at RDE orally, daily in combination with trametinib, in 21-day treatment cycles after a safety run-in. Part 2: Dose Expansion (Cohort B): VVD-159642 + Sotorasib VVD-159642 Participants will receive VVD-159642 at RDE orally, daily in combination with sotorasib, in 21-day treatment cycles after a safety run-in.
- Primary Outcome Measures
Name Time Method Part 2: Incidence and Severity of Clinically Significant Changes in Laboratory Evaluations Up to approximately 29 months Part 1: Incidence and Severity of Dose-limiting Toxicities (DLTs) 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) Up to approximately 29 months Part 2: Incidence and Severity of Clinically Significant Changes in Vital Signs Up to approximately 29 months
- Secondary Outcome Measures
Name Time Method Part 1: Recommended Dose for Expansion (RDE) of VVD-159642 as a Single Agent 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.
Part 2: Recommended Phase 2 Dose (RP2D) of VVD-159642 as a Single Agent and in Combination with Sotorasib and Trametinib 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.
Part 2: Overall Response Rate (ORR) 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.
Part 2: Duration of Response (DoR) 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.
Part 2: Progression-free Survival (PFS) 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.
Part 2: Disease Control Rate (DCR) 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.
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 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 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 Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days)
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Trial Locations
- Locations (8)
START Mid West
🇺🇸Grand Rapids, Michigan, United States
START San Antonio
🇺🇸San Antonio, Texas, United States
START Mountain
🇺🇸Ogden, Utah, United States
NEXT Austin
🇺🇸Austin, Texas, United States
NEXT Dallas
🇺🇸Irving, Texas, United States
NEXT San Antonio
🇺🇸San Antonio, Texas, United States
NEXT Virginia
🇺🇸Fairfax, Virginia, United States
Linear Clinical
🇦🇺Nedlands, Western Australia, Australia