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

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

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 Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: VVD-159642; Drug: Sotorasib; Drug: Trametinib

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Vividion Clinical Trial Call Center; Phone Number: 858-345-9752; Email: clinicaltrials@vividion.com

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Recruiting
      • Clinical Research South Australia (CRSA)
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Recruiting
      • Linear Clinical
• United States
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Recruiting
      • START Mid West
  • Texas
    • Austin, Texas, United States, 78758
      • Recruiting
      • NEXT Austin
    • Irving, Texas, United States, 75039
      • Recruiting
      • NEXT Dallas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • START San Antonio
    • San Antonio, Texas, United States, 78299
      • Recruiting
      • NEXT San Antonio
  • Utah
    • Ogden, Utah, United States, 84401
      • Recruiting
      • START Mountain
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • NEXT Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Dose Escalation: VVD-159642 Single Agent; Participants will receive ascending doses of VVD-159642, orally, daily in 21-day treatment cycles during Part 1.	Drug: VVD-159642; Oral capsules
Experimental: Part 2: Dose Expansion (Cohort A): VVD-159642 Single Agent; Participants will receive VVD-159642 at the recommended dose for expansion (RDE), orally, daily in 21-day treatment cycles during Part 2.	Drug: VVD-159642; Oral capsules
Experimental: Part 2: Dose Expansion (Cohort B): VVD-159642 + Sotorasib; Participants will receive VVD-159642 at RDE orally, daily in combination with sotorasib, in 21-day treatment cycles after a safety run-in.	Drug: VVD-159642; Oral capsules; Drug: Sotorasib; Oral tablets
Experimental: Part 2: Dose Expansion (Cohort C): VVD-159642 + Trametinib; Participants will receive VVD-159642 at RDE orally, daily in combination with trametinib, in 21-day treatment cycles after a safety run-in.	Drug: VVD-159642; Oral capsules; Drug: Trametinib; Oral tablets

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	Up to approximately 29 months
Part 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.	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.	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.	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		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)

Collaborators and Investigators

• Sponsor: Vividion Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: January 27, 2025
• First Submitted That Met QC Criteria: January 27, 2025
• First Posted (Actual): February 3, 2025

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: HER2; Phase I; solid tumors; KRAS G12C; KRAS; PI3K; MEK; RAS
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; trametinib; sotorasib
• Other Study ID Numbers: VVD-159642-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No