Advanced Solid Tumors
Conditions
Keywords
RAS, PI3K, KRAS, MEK, Phase I, solid tumors, KRAS G12C, HER2
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.
Interventions
DRUGVVD-159642
Oral capsules
DRUGSotorasib
Oral tablets
DRUGTrametinib
Oral tablets
Sponsors
Vividion Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
| Part 2: Incidence and Severity of Clinically Significant Changes in Laboratory Evaluations | Up to approximately 29 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | — |
Countries
Australia, United States
Contacts
CONTACTVividion Clinical Trial Call Center
Outcome results
None listed