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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

NCT06004245 · Vividion Therapeutics, Inc.
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Official title
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)
About this study
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 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 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; 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 * 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 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
Study design
Enrollment target: 280 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2024-01-25
Estimated completion: 2027-05-31
Last updated: 2026-04-07
Interventions
Drug: VVD-133214Drug: PembrolizumabDrug: Bevacizumab
Primary outcomes
  • Incidence of Adverse Events, with Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0) (From first dose of study drug(s) until 30 days after the final dose of VVD-133214 or 90 days after last dose of bevacizumab or pembrolizumab)
  • Incidence of Dose-Limiting Toxicities (Cycle 1 (1 cycle is 3 weeks))
Sponsor
Vividion Therapeutics, Inc. · industry
Contacts & investigators
ContactVividion Clinical Trial Call Center · contact · clinicaltrials@vividion.com · 1+ 858-345-9752 (U.S. Only)
InvestigatorClinical Trials · study_director, Vividion Therapeutics
All locations (29)
City of Hope Cancer CenterRecruiting
Duarte, California, United States
City of Hope at Irvine LennarRecruiting
Irvine, California, United States
Emory University School of MedicineRecruiting
Atlanta, Georgia, United States
Norton Cancer Institute - MDCActive Not Recruiting
Louisville, Kentucky, United States
Rutgers Cancer Institute of New JerseyRecruiting
New Brunswick, New Jersey, United States
Duke UniversityCompleted
Durham, North Carolina, United States
Oklahoma University Health Sciences CenterActive Not Recruiting
Oklahoma City, Oklahoma, United States
SCRI Oncology PartnersActive Not Recruiting
Nashville, Tennessee, United States
MD Anderson Cancer CenterRecruiting
Houston, Texas, United States
St Vincents SydneyActive Not Recruiting
Darlinghurst, New South Wales, Australia
Alfred HospitalActive Not Recruiting
Melbourne, Victoria, Australia
UZ Leuven GasthuisbergActive Not Recruiting
Leuven, Belgium
BCCA-Vancouver Cancer CentreCompleted
Vancouver, British Columbia, Canada
Princess Margaret Cancer CenterActive Not Recruiting
Toronto, Ontario, Canada
RigshospitaletActive Not Recruiting
København Ø, Denmark
CLCC Leon Berard LyonCompleted
Lyon, France
Gustave RoussyActive Not Recruiting
Villejuif, France
Sarawak Public HospitalActive Not Recruiting
Kuching, Sarawak, Malaysia
Seoul National University Bundang HospitalActive Not Recruiting
Seongnam-si, South Korea
Seoul National University HospitalActive Not Recruiting
Seoul, South Korea
Asan Medical CenterActive Not Recruiting
Seoul, South Korea
Vall d'Hebron Institute of Oncology (VHIO), BarcelonaActive Not Recruiting
Barcelona, BARCELONA, Spain
Clinica Universidad de Navarra MadridActive Not Recruiting
Madrid, Madrid, Spain
START Madrid. Centro Integral Oncologico Clara CampalActive Not Recruiting
Madrid, Madrid, Spain
Clinica Universitaria de NavarraActive Not Recruiting
Pamplona, Navarre, Spain
Hospital Clinico Universitario de ValenciaActive Not Recruiting
Valencia, Valencia, Spain
Sarah Cannon Research InstituteActive Not Recruiting
London, United Kingdom
The ChristieActive Not Recruiting
Manchester, United Kingdom
Royal Marsden Hospital (Sutton)Active Not Recruiting
Sutton, United Kingdom
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 · TrialPath