A Study to Evaluate the Safety, Pharmacokinetics, and Anti-Tumor Activity of VVD-133214 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors

NCT ID: NCT06004245

Last Updated: 2025-12-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

295 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-01-25

Study Completion Date

2027-05-31

Brief Summary

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This is a first-in-human, Phase I, open-label, multicenter, dose-escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of VVD-133214 monotherapy, and in combination with pembrolizumab, in participants with microsatellite instability (MSI) and/or deficient mismatch repair (dMMR) advanced solid tumors. VVD-133214 is an oral drug that acts on a protein called Werner (WRN), which may promote the growth of cancers that are MSI and/or dMMR. By acting on WRN, VVD-133214 may be able to block the growth of these types of cancer.

Detailed Description

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Conditions

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Advanced Solid Tumors

Keywords

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Deficient mismatch repair dMMR Microsatellite instability MSI

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

This is an open label study. Participants will be assigned to dose cohorts in the order in which they are enrolled. However, if two or more cohorts in the same part of the study are open for enrollment at the same time, participants will be randomized into these cohorts.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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VVD-133214 Dose Escalation

Group Type EXPERIMENTAL

VVD-133214

Intervention Type DRUG

VVD-133214 will be administered orally and once daily (QD) in 3-week cycles.

VVD-133214 Monotherapy Expansion

Group Type EXPERIMENTAL

VVD-133214

Intervention Type DRUG

VVD-133214 will be administered orally and once daily (QD) in 3-week cycles.

VVD-133214 + Pembrolizumab Expansion

Group Type EXPERIMENTAL

VVD-133214

Intervention Type DRUG

VVD-133214 will be administered orally and once daily (QD) in 3-week cycles.

Pembrolizumab

Intervention Type DRUG

Pembrolizumab will be administered by intravenous (IV) infusion at a fixed dose of 200 mg on Day 1 of each 21-day cycle.

Interventions

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VVD-133214

VVD-133214 will be administered orally and once daily (QD) in 3-week cycles.

Intervention Type DRUG

Pembrolizumab

Pembrolizumab will be administered by intravenous (IV) infusion at a fixed dose of 200 mg on Day 1 of each 21-day cycle.

Intervention Type DRUG

Other Intervention Names

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KEYTRUDA®

Eligibility Criteria

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Inclusion Criteria

* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
* Have a microsatellite instability (MSI) and/or deficient mismatch repair (dMMR), histologically or cytologically documented advanced (unresectable and/or metastatic) solid tumor; for the combination with pembrolizumab only: Histologically confirmed locally advanced, or metastatic colorectal adenocarcinoma (CRC) with no prior systemic treatment for metastatic disease and not amenable to surgery
* Have received and then progressed following, or are intolerant to, standard therapy in the advanced setting
* Presence of measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
* Life expectancy of at least (≥)12 weeks
* Availability of formaldehyde-fixed paraffin-embedded (FFPE) archival tumor tissue for submission to Sponsor/central laboratory for retrospective central testing; for participants without archival tissue, a biopsy from either primary or metastatic tumor lesion, deemed medically feasible, must be taken
* Adequate hematologic, end-organ, and cardiovascular function, as defined in the protocol

Exclusion Criteria

* Inability or unwillingness to swallow pills
* Malabsorption syndrome or other condition that would interfere with enteral absorption
* Known hypersensitivity or intolerance to ingredients from the study drug formulation including patients with rare genetic disorders such as galactosaemia, glucose-galactose intolerance or congenital lactase deficiency
* Known uncontrolled central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control) and/or carcinomatous meningitis
* Known active or uncontrolled bacterial, viral, fungal, mycobacterial (including but not limited to tuberculosis and atypical mycobacterial disease), parasitic, or other infection (excluding fungal infections of nail beds), or any major episode of infection requiring treatment with intravenous antibiotics or hospitalization within 2 weeks prior to the start of drug administration (related to the completion of the course of antibiotics, except if for tumor fever) or 6 months for any intracranial abscess
* Has a positive test at screening for hepatitis B virus, hepatitis C virus, or for human immodeficiency virus (HIV), per local diagnostic standard and in accordance with local laws and regulations
* Uncontrolled diabetes or symptomatic hyperglycemia (i.e., well controlled defined as a screening hemoglobin A1c \<8% and no urinary ketoacidosis)
* Significant cardiovascular/cerebrovascular disease within 6 months prior to Day 1 of study drug administration
* Alcohol or drug dependence or abuse
* Patients with known Werner (WRN) syndrome
* Prior treatment with any WRN helicase inhibitor
* Treatment with moderate or strong CYP3A4 inducers within 14 days prior to initiation of study treatment
* Treatment with moderate or strong CYP3A4 or P-glycoprotein inhibitors within 14 days prior to initiation of study treatment
* Pregnancy, breastfeeding, or intention of becoming pregnant during the study


* Active or history of autoimmune disease or immune deficiency with some exceptions
* History of interstitial lung disease or pneumonitis
* Treatment with systemic immunosuppressive medication (such as corticosteroids) within 2 weeks prior to initiation of study treatment with some exceptions
* Treatment with organ transplant/graft tissue
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Vividion Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Vividion Therapeutics

Locations

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City of Hope Cancer Center

Duarte, California, United States

Site Status ACTIVE_NOT_RECRUITING

City of Hope - Santa Clarita

Valencia, California, United States

Site Status RECRUITING

Norton Cancer Institute - MDC

Louisville, Kentucky, United States

Site Status ACTIVE_NOT_RECRUITING

Duke University

Durham, North Carolina, United States

Site Status COMPLETED

Oklahoma University Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status ACTIVE_NOT_RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, United States

Site Status ACTIVE_NOT_RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status ACTIVE_NOT_RECRUITING

Alfred Hospital

Melbourne, Victoria, Australia

Site Status ACTIVE_NOT_RECRUITING

UZ Leuven Gasthuisberg

Leuven, , Belgium

Site Status ACTIVE_NOT_RECRUITING

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia, Canada

Site Status COMPLETED

Princess Margaret Cancer Center

Toronto, Ontario, Canada

Site Status ACTIVE_NOT_RECRUITING

Rigshospitalet

København Ø, , Denmark

Site Status ACTIVE_NOT_RECRUITING

CLCC Leon Berard Lyon

Lyon, , France

Site Status COMPLETED

Gustave Roussy

Villejuif, , France

Site Status ACTIVE_NOT_RECRUITING

Seoul National University Bundang Hospital

Seongnam-si, , South Korea

Site Status RECRUITING

Seoul National University Hospital

Seoul, , South Korea

Site Status RECRUITING

Asan Medical Center

Seoul, , South Korea

Site Status RECRUITING

Vall d'Hebron Institute of Oncology (VHIO), Barcelona

Barcelona, BARCELONA, Spain

Site Status ACTIVE_NOT_RECRUITING

Clinica Universidad de Navarra Madrid

Madrid, Madrid, Spain

Site Status ACTIVE_NOT_RECRUITING

START Madrid. Centro Integral Oncologico Clara Campal

Madrid, Madrid, Spain

Site Status ACTIVE_NOT_RECRUITING

Clinica Universitaria de Navarra

Pamplona, Navarre, Spain

Site Status COMPLETED

Hospital Clinico Universitario de Valencia

Valencia, Valencia, Spain

Site Status ACTIVE_NOT_RECRUITING

Sarah Cannon Research Institute

London, , United Kingdom

Site Status ACTIVE_NOT_RECRUITING

The Christie

Manchester, , United Kingdom

Site Status ACTIVE_NOT_RECRUITING

Royal Marsden Hospital (Sutton)

Sutton, , United Kingdom

Site Status COMPLETED

Countries

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United States Australia Belgium Canada Denmark France South Korea Spain United Kingdom

Central Contacts

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Vividion Clinical Trial Call Center

Role: CONTACT

Phone: 1+ 858-345-9752 (U.S. Only)

Email: [email protected]

Other Identifiers

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2023-503170-20-01

Identifier Type: REGISTRY

Identifier Source: secondary_id

VVD-133214-01

Identifier Type: -

Identifier Source: org_study_id