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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
220
START Mid West
Grand Rapids, Michigan, United States
RECRUITINGNEXT Austin
Austin, Texas, United States
RECRUITINGNEXT Dallas
Irving, Texas, United States
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
Part 1: Recommended Dose for Expansion (RDE) of VVD-159642 as a Single Agent
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.
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
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.
Time frame: Up to approximately 29 months
Part 2: Overall Response Rate (ORR)
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.
Time frame: Up to approximately 29 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
START San Antonio
San Antonio, Texas, United States
RECRUITINGNEXT San Antonio
San Antonio, Texas, United States
RECRUITINGSTART Mountain
Ogden, Utah, United States
RECRUITINGNEXT Virginia
Fairfax, Virginia, United States
RECRUITINGClinical Research South Australia (CRSA)
Adelaide, South Australia, Australia
RECRUITINGLinear Clinical
Nedlands, Western Australia, Australia
RECRUITINGPart 2: Duration of Response (DoR)
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.
Time frame: Up to approximately 29 months
Part 2: Progression-free Survival (PFS)
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.
Time frame: Up to approximately 29 months
Part 2: Disease Control Rate (DCR)
DCR is defined as the percentage of participants achieving CR or PR, or stable disease (SD) per RECIST version 1.1 by investigator assessment.
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)