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
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
Study locations (7)
START Mid West
Grand Rapids, Michigan, 49546
NEXT Austin
Austin, Texas, 78758
NEXT Dallas
Irving, Texas, 75039
START San Antonio
San Antonio, Texas, 78229
NEXT San Antonio
San Antonio, Texas, 78299
START Mountain
Ogden, Utah, 84401
NEXT Virginia
Fairfax, Virginia, 22031