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

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

Overview

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

• Drug VVD-159642
  Oral capsules
• Drug Sotorasib
  Oral tablets
• Drug Trametinib
  Oral tablets

Primary outcome measures

• 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 outcome measures (9)

• 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

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.

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 7 centers

• START Mid West — Grand Rapids
• NEXT Austin — Austin
• NEXT Dallas — Irving
• START San Antonio — San Antonio
• NEXT San Antonio — San Antonio
• START Mountain — Ogden
• NEXT Virginia — Fairfax

Australia · 2 centers

• Clinical Research South Australia (CRSA) — Adelaide
• Linear Clinical — Nedlands

Identifiers

NCT: NCT06804824 · VVD-159642-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗