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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