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NCT06004245From ClinicalTrials.govRecruiting

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

A Phase I, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Anti-Tumor Activity of VVD-133214 as Monotherapy and in Combination in Participants With Advanced Solid Tumors Harboring Microsatellite Instability (MSI) and/or Deficient Mismatch Repair (dMMR)

  • Advanced Solid Tumors
  • Colorectal Cancer

At a glance

Phase
Phase 1
Study type
Interventional
Sponsor
Vividion Therapeutics, Inc.
Enrolment target
280
Started
25 January 2024
Main results due
31 May 2027
Study sites
47
Registry updated
25 September 2026

Can you take part?

  • Aged 18 years and over.
  • Open to any sex.
  • You need the condition being studied — healthy volunteers are not accepted.

These are the headline rules only. Every study has a longer list, and whether you are eligible is decided by the research team at the site — never by this page.

Read the full eligibility criteria
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 monotherapy only (solid tumor): Have received and then progressed following or are intolerant to at least 2 standard treatment regimens in the advanced setting including standard chemotherapy or checkpoint inhibitors according to tumor type.
* For the combination with bevacizumab only: Advanced, or metastatic colorectal adenocarcinoma (CRC) treated with at least 2 but no more than 3 prior lines of systemic therapy for the treatment of advanced CRC and demonstrated progressive disease or intolerance to the last regimen. Prior treatment regimens must have included (unless not eligible for or intolerant to any of these agents): An immune checkpoint inhibitor (if available as standard of care), Fluoropyrimidine, Irinotecan and/or oxaliplatin, +/- an anti-VEGF monoclonal antibody, Participants with RAS WT tumors may have received anti-epidermal growth factor receptor (EGFR) monoclonal antibody based on Investigator discretion. Treatment with adjuvant/neoadjuvant chemotherapy and/or immunotherapy will count as a line of therapy for advanced disease if progression occurred during or within 12 months of completing the treatment.
* For the combination with pembrolizumab only: Histologically confirmed locally advanced, or metastatic CRC with no prior systemic treatment for metastatic disease and not amenable to surgery.
* 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

Additional Exclusion Criteria for the Combination with Bevacizumab Only:

* Had major surgery within 4 weeks prior to study drug administration
* Deep venous thrombosis (DVT) or pulmonary embolism (PE) within 12 weeks prior to study drug administration
* Known coagulopathy that increases the risk of bleeding
* Patients with Grade 2+ proteinuria (exception: if 24-hour urinary protein is less than 1.0 gm/24 hours)

Additional Exclusion Criteria for the Combination with Pembrolizumab Only:

* 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

What this study is about

In the sponsor’s own words, from the registry.

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 bevacizumab or 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.

Study sites(47)

  • University of Arizona Cancer Center

    Tucson, Arizona, United States

    Not yet recruiting

  • City of Hope Cancer Center

    Duarte, California, United States

    Recruiting

  • City of Hope at Irvine Lennar

    Irvine, California, United States

    Recruiting

  • START Los Angeles

    Los Angeles, California, United States

    Recruiting

  • Emory University School of Medicine

    Atlanta, Georgia, United States

    Recruiting

  • University of Chicago

    Chicago, Illinois, United States

    Not yet recruiting

  • Norton Cancer Institute - MDC

    Louisville, Kentucky, United States

    Recruiting

  • University of Michigan

    Ann Arbor, Michigan, United States

    Recruiting

  • START Midwest

    Grand Rapids, Michigan, United States

    Recruiting

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, United States

    Recruiting

  • Duke University

    Durham, North Carolina, United States

    Completed

  • Oklahoma University Health Sciences Center

    Oklahoma City, Oklahoma, United States

    Active, not recruiting

  • SCRI Oncology Partners

    Nashville, Tennessee, United States

    Recruiting

  • MD Anderson Cancer Center

    Houston, Texas, United States

    Recruiting

  • START San Antonio

    San Antonio, Texas, United States

    Recruiting

  • START Mountain Region

    West Valley City, Utah, United States

    Recruiting

  • St Vincents Sydney

    Darlinghurst, New South Wales, Australia

    Recruiting

  • Alfred Hospital

    Melbourne, Victoria, Australia

    Recruiting

  • UZ Leuven Gasthuisberg

    Leuven, Belgium

    Recruiting

  • BCCA-Vancouver Cancer Centre

    Vancouver, British Columbia, Canada

    Completed

  • Princess Margaret Cancer Center

    Toronto, Ontario, Canada

    Recruiting

  • Zhejiang Cancer Hospital

    Hangzhou, Zhejiang, China

    Not yet recruiting

  • Beijing Cancer Hospital

    Beijing, China

    Recruiting

  • The Sixth Hospital, affiliated with Sun Yat-sen University

    Guangzhou, China

    Not yet recruiting

  • Rigshospitalet

    København Ø, Denmark

    Recruiting

  • CLCC Leon Berard Lyon

    Lyon, France

    Completed

  • Gustave Roussy

    Villejuif, France

    Recruiting

  • Sarawak Public Hospital

    Kuching, Sarawak, Malaysia

    Recruiting

  • Kyungpook National University Chilgok Hospital

    Daegu, South Korea

    Not yet recruiting

  • National Cancer Center

    Gyeonggi-do, South Korea

    Not yet recruiting

  • Seoul National University Bundang Hospital

    Seongnam-si, South Korea

    Recruiting

  • Seoul National University Hospital

    Seoul, South Korea

    Recruiting

  • Asan Medical Center

    Seoul, South Korea

    Active, not recruiting

  • Samsung Medical Center

    Seoul, South Korea

    Recruiting

  • Severance Hospital

    Seoul, South Korea

    Recruiting

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

    Barcelona, BARCELONA, Spain

    Recruiting

  • Clinica Universidad de Navarra Madrid

    Madrid, Madrid, Spain

    Recruiting

  • START Madrid. Centro Integral Oncologico Clara Campal

    Madrid, Madrid, Spain

    Recruiting

  • Clinica Universitaria de Navarra

    Pamplona, Navarre, Spain

    Recruiting

  • Hospital Clinico Universitario de Valencia

    Valencia, Valencia, Spain

    Recruiting

  • NEXT Oncology - Barcelona

    Barcelona, Spain

    Not yet recruiting

  • START Barcelona

    Barcelona, Spain

    Not yet recruiting

  • Start Madrid-FJD, Hospital Fundacion Jimenez Diaz

    Madrid, Spain

    Not yet recruiting

  • NEXT Oncology-Hospital Universitario Quironsalud Madrid

    Madrid, Spain

    Not yet recruiting

  • Sarah Cannon Research Institute

    London, United Kingdom

    Recruiting

  • The Christie

    Manchester, United Kingdom

    Recruiting

  • Royal Marsden Hospital (Sutton)

    Sutton, United Kingdom

    Recruiting

Showing 47 of 47 sites. 32 of the 47 sites on this study are recruiting right now — a site can stop enrolling while the study as a whole is still open.

Source: ClinicalTrials.gov record NCT06004245. Trialion does not run this study, is not paid to refer anyone to it, and cannot enrol you. Eligibility is always decided by the research team at the site.

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A Study to Evaluate the Safety, Pharmacokinetics, and Anti-Tumor Activity of VVD-133214 as Monotherapy and in | Trialion