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

March 16, 2026 updated by: Vividion Therapeutics, Inc.

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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
220

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
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]
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
Up to approximately 29 months
Part 2: Incidence and Severity of Clinically Significant Changes in Vital Signs
Time Frame: Up to approximately 29 months
Up to approximately 29 months
Part 2: Incidence and Severity of Clinically Significant Changes in Laboratory Evaluations
Time Frame: Up to approximately 29 months
Up to approximately 29 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Part 1: Recommended Dose for Expansion (RDE) of VVD-159642 as a Single Agent
Time Frame: 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.
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
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)
Time Frame: 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.
Up to approximately 29 months
Part 2: Duration of Response (DoR)
Time Frame: 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.
Up to approximately 29 months
Part 2: Progression-free Survival (PFS)
Time Frame: 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.
Up to approximately 29 months
Part 2: Disease Control Rate (DCR)
Time Frame: 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.
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)
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)
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)
Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Vividion Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 25, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 27, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 27, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 3, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 18, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 16, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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