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

Last updated: July 21, 2026
Sponsor: Vividion Therapeutics, Inc.
Overall Status: Active - Recruiting

Phase

1

Condition

Rectal Cancer

Colon Cancer

Colon Cancer; Rectal Cancer

Treatment

RO7589831

Pembrolizumab

Bevacizumab

Clinical Study ID

NCT06004245
VVD-133214-01
2023-503170-20-01
2023-503170-20-00
  • Ages > 18
  • All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

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 bevacizumab only: advanced, or metastaticcolorectal adenocarcinoma (CRC) treated with at least 2 but no more than 3 priorlines of systemic therapy for the treatment of advanced CRC; For the combinationwith pembrolizumab only: Histologically confirmed locally advanced, or metastaticCRC with no prior systemic treatment for metastatic disease and not amenable tosurgery

  • Have received and then progressed following, or are intolerant to, standard therapyin the advanced setting

  • Presence of measurable disease according to Response Evaluation Criteria in SolidTumors (RECIST) version 1.1

  • Life expectancy of at least (≥)12 weeks

  • Availability of formaldehyde-fixed paraffin-embedded (FFPE) archival tumor tissuefor submission to Sponsor/central laboratory for retrospective central testing; forparticipants without archival tissue, a biopsy from either primary or metastatictumor lesion, deemed medically feasible, must be taken

  • Adequate hematologic, end-organ, and cardiovascular function, as defined in theprotocol

Exclusion

Exclusion Criteria:

  • Inability or unwillingness to swallow pills

  • Malabsorption syndrome or other condition that would interfere with enteralabsorption

  • Known hypersensitivity or intolerance to ingredients from the study drug formulationincluding patients with rare genetic disorders such as galactosaemia,glucose-galactose intolerance or congenital lactase deficiency

  • Known uncontrolled central nervous system (CNS) metastases (progressing or requiringanticonvulsants or corticosteroids for symptomatic control) and/or carcinomatousmeningitis

  • Known active or uncontrolled bacterial, viral, fungal, mycobacterial (including butnot limited to tuberculosis and atypical mycobacterial disease), parasitic, or otherinfection (excluding fungal infections of nail beds), or any major episode ofinfection requiring treatment with intravenous antibiotics or hospitalization within 2 weeks prior to the start of drug administration (related to the completion of thecourse of antibiotics, except if for tumor fever) or 6 months for any intracranialabscess

  • Has a positive test at screening for hepatitis B virus, hepatitis C virus, or forhuman immodeficiency virus (HIV), per local diagnostic standard and in accordancewith local laws and regulations

  • Uncontrolled diabetes or symptomatic hyperglycemia (i.e., well controlled defined asa screening hemoglobin A1c <8% and no urinary ketoacidosis)

  • Significant cardiovascular/cerebrovascular disease within 6 months prior to Day 1 ofstudy 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 initiationof study treatment

  • Treatment with moderate or strong CYP3A4 or P-glycoprotein inhibitors within 14 daysprior 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 tostudy drug administration

  • Known coagulopathy that increases the risk of bleeding

  • Patients with Grade 2+ proteinuria (exception: if 24-hour urinary protein is lessthan 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

Study Design

Total Participants: 280
Treatment Group(s): 4
Primary Treatment: RO7589831
Phase: 1
Study Start date:
January 25, 2024
Estimated Completion Date:
May 31, 2027

Connect with a study center

  • St Vincents Sydney

    Darlinghurst, New South Wales 2010
    Australia

    Active - Recruiting

  • Alfred Hospital

    Melbourne, Victoria 3181
    Australia

    Active - Recruiting

  • UZ Leuven Gasthuisberg

    Leuven, 3000
    Belgium

    Active - Recruiting

  • BCCA-Vancouver Cancer Centre

    Vancouver, British Columbia V5Z 4E6
    Canada

    Completed

  • Princess Margaret Cancer Center

    Toronto, Ontario M5G 2M9
    Canada

    Active - Recruiting

  • Rigshospitalet

    København Ø, 2100
    Denmark

    Active - Recruiting

  • Rigshospitalet; Onkologisk Klinik

    København Ø, 2100
    Denmark

    Active - Recruiting

  • CLCC Leon Berard Lyon

    Lyon, 69008
    France

    Completed

  • Gustave Roussy

    Villejuif, 94805
    France

    Active - Recruiting

  • Asan Medical Center

    Seoul, 05505
    Korea, Republic of

    Active - Recruiting

  • Sarawak Public Hospital

    Kuching, Sarawak 93586
    Malaysia

    Active - Recruiting

  • Kyungpook National University Chilgok Hospital

    Daegu, 41404
    South Korea

    Site Not Available

  • National Cancer Center

    Gyeonggi-do, 10408
    South Korea

    Site Not Available

  • Seoul National University Bundang Hospital

    Seongnam-si, 13620
    South Korea

    Site Not Available

  • Asan Medical Center

    Seoul, 05505
    South Korea

    Site Not Available

  • Samsung Medical Center

    Seoul, 06355
    South Korea

    Site Not Available

  • Seoul National University Hospital

    Seoul, 03080
    South Korea

    Active - Recruiting

  • Severance Hospital

    Seoul, 33732
    South Korea

    Site Not Available

  • Asan Medical Center

    Seoul 1835848, 05505
    South Korea

    Active - Recruiting

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

    Barcelona, BARCELONA 08035
    Spain

    Active - Recruiting

  • Clinica Universidad de Navarra Madrid

    Madrid, Madrid 28027
    Spain

    Active - Recruiting

  • START Madrid. Centro Integral Oncologico Clara Campal

    Madrid, Madrid 28050
    Spain

    Active - Recruiting

  • Clinica Universidad de Navarra Madrid

    Madrid 3117735, Madrid 3117732 28027
    Spain

    Site Not Available

  • Clinica Universitaria de Navarra; Servicio de Oncologia

    Pamplona, Navarra 31008
    Spain

    Active - Recruiting

  • Clinica Universitaria de Navarra

    Pamplona, Navarre 31008
    Spain

    Site Not Available

  • Hospital Clinico Universitario de Valencia

    Valencia, Valencia 46010
    Spain

    Site Not Available

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

    Barcelona 3128760, 08035
    Spain

    Site Not Available

  • Clinica Universidad de Navarra Madrid; Servicio de Oncología

    Madrid, 28027
    Spain

    Active - Recruiting

  • START Madrid. Centro Integral Oncologico Clara Campal; CIOCC

    Madrid, 28050
    Spain

    Active - Recruiting

  • START Madrid. Centro Integral Oncologico Clara Campal

    Madrid 3117735, 28050
    Spain

    Site Not Available

  • Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

    Valencia, 46010
    Spain

    Active - Recruiting

  • Hospital Clinico Universitario de Valencia

    Valencia 2509954, 46010
    Spain

    Site Not Available

  • Royal Marsden Hospital - Fulham

    London, SW3 6JJ
    United Kingdom

    Active - Recruiting

  • Sarah Cannon Research Institute

    London, W1G 6AD
    United Kingdom

    Active - Recruiting

  • The Christie

    Manchester, M20 4BX
    United Kingdom

    Site Not Available

  • Royal Marsden Hospital (Sutton)

    Sutton, SM2 5PT
    United Kingdom

    Active - Recruiting

  • City of Hope

    Duarte, California 91010
    United States

    Active - Recruiting

  • City of Hope Cancer Center

    Duarte, California 91010
    United States

    Active - Recruiting

  • City of Hope at Irvine Lennar

    Irvine, California 91355
    United States

    Active - Recruiting

  • START Los Angeles

    Los Angeles, California 90025
    United States

    Site Not Available

  • Emory University School of Medicine

    Atlanta, Georgia 30322
    United States

    Active - Recruiting

  • Norton Cancer Institute - MDC

    Louisville, Kentucky 40202
    United States

    Active - Recruiting

  • University of Michigan

    Ann Arbor, Michigan 48109
    United States

    Site Not Available

  • START Midwest

    Grand Rapids, Michigan 49546
    United States

    Site Not Available

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey 08901
    United States

    Active - Recruiting

  • Duke University

    Durham, North Carolina 27705
    United States

    Completed

  • Duke University; Office of Research Contracts

    Durham, North Carolina 27705
    United States

    Active - Recruiting

  • Oklahoma University Health Sciences Center

    Oklahoma City, Oklahoma 73170
    United States

    Active - Recruiting

  • Stephenson Cancer Center Investigational Pharmacy

    Oklahoma City, Oklahoma 73104
    United States

    Site Not Available

  • SCRI Oncology Partners

    Nashville, Tennessee 37203
    United States

    Active - Recruiting

  • MD Anderson Cancer Center

    Houston, Texas 77030
    United States

    Active - Recruiting

  • START San Antonio

    San Antonio, Texas 78229
    United States

    Site Not Available

  • START Mountain Region

    West Valley City, Utah 84119
    United States

    Site Not Available

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