RECRUITING Phase 1 ClinicalTrials.gov

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

Sponsor: Vividion Therapeutics, Inc. • ClinicalTrials.gov ID: NCT06004245

Registry updated: 2026-10-21

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Description

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.

Interventions

VVD-133214 (Drug)
VVD-133214 will be administered orally and once daily (QD) in 3-week cycles.
Pembrolizumab (Drug)
Pembrolizumab will be administered by intravenous (IV) infusion at a fixed dose of 200 mg on Day 1 of each 21-day cycle.
Bevacizumab (Drug)
Bevacizumab will be administered by intravenous (IV) infusion at a fixed dose of 7.5 mg/kg on Day 1 of each 21-day cycle.

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

Conditions

Advanced Solid Tumors Colorectal Cancer

Locations

University of Arizona Cancer Center — Tucson, Arizona, United States
City of Hope Cancer Center — Duarte, California, United States
City of Hope at Irvine Lennar — Irvine, California, United States
START Los Angeles — Los Angeles, California, United States
The Angeles Clinic and Research Institute — Los Angeles, California, United States
Emory University School of Medicine — Atlanta, Georgia, United States
University of Chicago — Chicago, Illinois, United States
Norton Cancer Institute - MDC — Louisville, Kentucky, United States
University of Michigan — Ann Arbor, Michigan, United States
START Midwest — Grand Rapids, Michigan, United States
Rutgers Cancer Institute of New Jersey — New Brunswick, New Jersey, United States
Duke University — Durham, North Carolina, United States
Oklahoma University Health Sciences Center — Oklahoma City, Oklahoma, United States
SCRI Oncology Partners — Nashville, Tennessee, United States
MD Anderson Cancer Center — Houston, Texas, United States
START San Antonio — San Antonio, Texas, United States
START Mountain Region — West Valley City, Utah, United States
West Virginia University Cancer Institute — Morgantown, West Virginia, United States
St Vincents Sydney — Darlinghurst, New South Wales, Australia
Alfred Hospital — Melbourne, Victoria, Australia
Cliniques universitaires de Saint Luc — Brussels, Belgium
UZ Leuven Gasthuisberg — Ghent, Belgium
UZ Gent — Ghent, Belgium
BCCA-Vancouver Cancer Centre — Vancouver, British Columbia, Canada
Princess Margaret Cancer Center — Toronto, Ontario, Canada
Zhejiang Cancer Hospital — Hangzhou, Zhejiang, China
Beijing Cancer Hospital — Beijing, China
The Sixth Hospital, affiliated with Sun Yat-sen University — Guangzhou, China
Rigshospitalet — København Ø, Denmark
CLCC Leon Berard Lyon — Lyon, France
Institut regional du Cancer de Montpellier — Montpellier, France
Hôpital saint Antoine — Paris, France
Hopital europeen Georges Pompidou — Paris, France
Oncopole Claudius Regaud — Toulouse, France
Gustave Roussy — Villejuif, France
Sarawak Public Hospital — Kuching, Sarawak, Malaysia
Kyungpook National University Chilgok Hospital — Daegu, South Korea
National Cancer Center — Gyeonggi-do, South Korea
Seoul National University Bundang Hospital — Seongnam-si, South Korea
Seoul National University Hospital — Seoul, South Korea
Asan Medical Center — Seoul, South Korea
Samsung Medical Center — Seoul, South Korea
Severance Hospital — Seoul, South Korea
Vall d'Hebron Institute of Oncology (VHIO), Barcelona — Barcelona, BARCELONA, Spain
Clinica Universidad de Navarra Madrid — Madrid, Madrid, Spain
START Madrid. Centro Integral Oncologico Clara Campal — Madrid, Madrid, Spain
Clinica Universitaria de Navarra — Pamplona, Navarre, Spain
Hospital Clinico Universitario de Valencia — Valencia, Valencia, Spain
NEXT Oncology - Barcelona — Barcelona, Spain
START Barcelona — Barcelona, Spain
Start Madrid-FJD, Hospital Fundacion Jimenez Diaz — Madrid, Spain
NEXT Oncology-Hospital Universitario Quironsalud Madrid — Madrid, Spain
Sarah Cannon Research Institute — London, United Kingdom
The Christie — Manchester, United Kingdom
Royal Marsden Hospital (Sutton) — Sutton, United Kingdom

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Official Source

Data sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

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