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)

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 Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Advanced Solid Tumors
• Intervention / Treatment: Drug: Pembrolizumab; Drug: VVD-133214; Drug: Bevacizumab

• Study Type: Interventional
• Enrollment (Estimated): 280
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Vividion Clinical Trial Call Center; Phone Number: 1+ 858-345-9752 (U.S. Only); Email: clinicaltrials@vividion.com

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Active, not recruiting
      • St Vincents Sydney
  • Victoria
    • Melbourne, Victoria, Australia, 3181
      • Recruiting
      • Alfred Hospital
• Belgium
  • Leuven, Belgium, 3000
    • Active, not recruiting
    • UZ Leuven Gasthuisberg
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Completed
      • BCCA-Vancouver Cancer Centre
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Active, not recruiting
      • Princess Margaret Cancer Center
• Denmark
  • København Ø, Denmark, 2100
    • Active, not recruiting
    • Rigshospitalet
• France
  • Lyon, France, 69008
    • Completed
    • CLCC Leon Berard Lyon
  • Villejuif, France, 94805
    • Active, not recruiting
    • Gustave Roussy
• Malaysia
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Active, not recruiting
      • Sarawak Public Hospital
• South Korea
  • Seongnam-si, South Korea, 13620
    • Active, not recruiting
    • Seoul National University Bundang Hospital
  • Seoul, South Korea, 03080
    • Active, not recruiting
    • Seoul National University Hospital
  • Seoul, South Korea, 05505
    • Active, not recruiting
    • Asan Medical Center
• Spain
  • BARCELONA
    • Barcelona, BARCELONA, Spain, 08035
      • Active, not recruiting
      • Vall d'Hebron Institute of Oncology (VHIO), Barcelona
  • Madrid
    • Madrid, Madrid, Spain, 28027
      • Active, not recruiting
      • Clinica Universidad de Navarra Madrid
    • Madrid, Madrid, Spain, 28050
      • Active, not recruiting
      • START Madrid. Centro Integral Oncologico Clara Campal
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Active, not recruiting
      • Clinica Universitaria de Navarra
  • Valencia
    • Valencia, Valencia, Spain, 46010
      • Active, not recruiting
      • Hospital Clinico Universitario de Valencia
• United Kingdom
  • London, United Kingdom, W1G 6AD
    • Recruiting
    • Sarah Cannon Research Institute
  • Manchester, United Kingdom, M20 4BX
    • Active, not recruiting
    • The Christie
  • Sutton, United Kingdom, SM2 5PT
    • Active, not recruiting
    • Royal Marsden Hospital (Sutton)
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope Cancer Center
    • Irvine, California, United States, 91355
      • Recruiting
      • City of Hope at Irvine Lennar
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University School of Medicine
      • Contact: Vividion Clinical Trial Call Center; Phone Number: +1 8583459752; Email: clinicaltrials@vividion.com
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • Norton Cancer Institute - MDC
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Recruiting
      • Rutgers Cancer Institute of New Jersey
      • Contact: Vividion Clinical Trial Call Center; Phone Number: +1 8583459752; Email: clinicaltrials@vividion.com
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Completed
      • Duke University
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73170
      • Recruiting
      • Oklahoma University Health Sciences Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • SCRI Oncology Partners
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VVD-133214 Dose Escalation	Drug: VVD-133214; VVD-133214 will be administered orally and once daily (QD) in 3-week cycles.
Experimental: VVD-133214 Monotherapy Expansion	Drug: VVD-133214; VVD-133214 will be administered orally and once daily (QD) in 3-week cycles.
Experimental: VVD-133214 + Pembrolizumab Expansion	Drug: Pembrolizumab; Pembrolizumab will be administered by intravenous (IV) infusion at a fixed dose of 200 mg on Day 1 of each 21-day cycle.; Other Names: KEYTRUDA®; Drug: VVD-133214; VVD-133214 will be administered orally and once daily (QD) in 3-week cycles.
Experimental: VVD-133214 + Bevacizumab Expansion	Drug: VVD-133214; VVD-133214 will be administered orally and once daily (QD) in 3-week cycles.; Drug: Bevacizumab; 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.; Other Names: Avastin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of Dose-Limiting Toxicities	Cycle 1 (1 cycle is 3 weeks)
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

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate	From start of study treatment until end of follow-up (up to approximately 36 months)
Disease Control Rate	From start of study treatment until end of follow-up (up to approximately 36 months)
Duration of Response	From the time of first occurrence of a documented response until the time of documented disease progression or death from any cause, whichever occurs first (up to approximately 36 months)
Progression-Free Survival, as Assessed by the Investigator	From start of study treatment to the first occurrence of documented disease progression or death from any cause, whichever occurs first (up to approximately 36 months)
Overall Survival	From start of study treatment to the time of death from any cause (up to approximately 36 months)
Maximum Plasma Concentration Observed (Cmax) of VVD-133214	At prespecified timepoints in Cycles 1, 2, and 3, and every 2 cycles thereafter (1 cycle is 3 weeks) until last dose of study drug (up to approximately 15 months)
Time of Maximum Plasma Concentration Observed (Tmax) of VVD-133214	At prespecified timepoints in Cycles 1, 2, and 3, and every 2 cycles thereafter (1 cycle is 3 weeks) until last dose of study drug (up to approximately 15 months)
Area Under the Plasma Concentration-Time Curve (AUC) of VVD-133214	At prespecified timepoints in Cycles 1, 2, and 3, and every 2 cycles thereafter (1 cycle is 3 weeks) until last dose of study drug (up to approximately 15 months)
Apparent Oral Clearance (CL/F) of VVD-133214	At prespecified timepoints in Cycles 1, 2, and 3, and every 2 cycles thereafter (1 cycle is 3 weeks) until last dose of study drug (up to approximately 15 months)
Volume of Distribution (V/F) of VVD-133214	At prespecified timepoints in Cycles 1, 2, and 3, and every 2 cycles thereafter (1 cycle is 3 weeks) until last dose of study drug (up to approximately 15 months)
Terminal Half-Life (T1/2) of VVD-133214	At prespecified timepoints in Cycles 1, 2, and 3, and every 2 cycles thereafter (1 cycle is 3 weeks) until last dose of study drug (up to approximately 15 months)

Collaborators and Investigators

• Sponsor: Vividion Therapeutics, Inc.
• Investigators: Study Director: Clinical Trials, Vividion Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2024
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027

Study Registration Dates

• First Submitted: August 16, 2023
• First Submitted That Met QC Criteria: August 16, 2023
• First Posted (Actual): August 22, 2023

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: MSI; dMMR; Microsatellite instability; Deficient mismatch repair
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Genomic Instability; Pathological Conditions, Signs and Symptoms; Colorectal Neoplasms; Microsatellite Instability; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Bevacizumab; pembrolizumab
• Other Study ID Numbers: VVD-133214-01; 2023-503170-20-01 (Registry Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

For eligible studies, qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/).

Roche's Global Policy on the Sharing of Clinical Information describes studies which are eligible for data sharing and how to request access (https://www.roche.com/innovation/process/clinical-trials/data-sharing/).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No