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 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: VVD-133214-012023-503170-20-01
• Study Type: interventional
• Target: 280
• Locations: 10 countries
• Sites: 38

Brief 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.

Conditions

Colorectal Cancer; Advanced Solid Tumors

Keywords

Deficient mismatch repair; dMMR; Microsatellite instability; MSI

Outcome Measures

Primary Outcomes (2)

• 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)

Secondary Outcomes (11)

• 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)

Study Arms (4)

VVD-133214 Dose Escalation

EXPERIMENTAL

Drug: VVD-133214

VVD-133214 Monotherapy Expansion

EXPERIMENTAL

Drug: VVD-133214

VVD-133214 + Pembrolizumab Expansion

EXPERIMENTAL

Drug: VVD-133214; Drug: Pembrolizumab

VVD-133214 + Bevacizumab Expansion

EXPERIMENTAL

Drug: VVD-133214; Drug: Bevacizumab

Interventions

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.

Also known as: Avastin

VVD-133214 + Bevacizumab Expansion

VVD-133214 DRUG

VVD-133214 will be administered orally and once daily (QD) in 3-week cycles.

VVD-133214 + Bevacizumab Expansion; VVD-133214 + Pembrolizumab Expansion; VVD-133214 Dose Escalation; VVD-133214 Monotherapy Expansion

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.

Also known as: KEYTRUDA®

VVD-133214 + Pembrolizumab Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Had major surgery within 4 weeks prior to study drug administration

Sponsors & Collaborators

• Vividion Therapeutics, Inc.: lead

Study Sites (38)

City of Hope Cancer Center

Duarte, California, 91010, United States

RECRUITING

City of Hope at Irvine Lennar

Irvine, California, 91355, United States

RECRUITING

START Los Angeles

Los Angeles, California, 90025, United States

NOT YET RECRUITING

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

RECRUITING

Norton Cancer Institute - MDC

Louisville, Kentucky, 40202, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

NOT YET RECRUITING

START Midwest

Grand Rapids, Michigan, 49546, United States

NOT YET RECRUITING

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

RECRUITING

Duke University

Durham, North Carolina, 27705, United States

COMPLETED

Oklahoma University Health Sciences Center

Oklahoma City, Oklahoma, 73170, United States

RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

START San Antonio

San Antonio, Texas, 78229, United States

NOT YET RECRUITING

START Mountain Region

West Valley City, Utah, 84119, United States

NOT YET RECRUITING

St Vincents Sydney

Darlinghurst, New South Wales, 2010, Australia

RECRUITING

Alfred Hospital

Melbourne, Victoria, 3181, Australia

RECRUITING

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

RECRUITING

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

COMPLETED

Princess Margaret Cancer Center

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

Rigshospitalet

København Ø, 2100, Denmark

RECRUITING

CLCC Leon Berard Lyon

Lyon, 69008, France

COMPLETED

Gustave Roussy

Villejuif, 94805, France

RECRUITING

Sarawak Public Hospital

Kuching, Sarawak, 93586, Malaysia

RECRUITING

Kyungpook National University Chilgok Hospital

Daegu, 41404, South Korea

NOT YET RECRUITING

National Cancer Center

Gyeonggi-do, 10408, South Korea

NOT YET RECRUITING

Seoul National University Bundang Hospital

Seongnam-si, 13620, South Korea

ACTIVE NOT RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

ACTIVE NOT RECRUITING

Samsung Medical Center

Seoul, 06355, South Korea

NOT YET RECRUITING

Severance Hospital

Seoul, 33732, South Korea

NOT YET RECRUITING

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

Barcelona, BARCELONA, 08035, Spain

RECRUITING

Clinica Universidad de Navarra Madrid

Madrid, Madrid, 28027, Spain

RECRUITING

START Madrid. Centro Integral Oncologico Clara Campal

Madrid, Madrid, 28050, Spain

RECRUITING

Clinica Universitaria de Navarra

Pamplona, Navarre, 31008, Spain

ACTIVE NOT RECRUITING

Hospital Clinico Universitario de Valencia

Valencia, Valencia, 46010, Spain

ACTIVE NOT RECRUITING

Sarah Cannon Research Institute

London, W1G 6AD, United Kingdom

RECRUITING

The Christie

Manchester, M20 4BX, United Kingdom

ACTIVE NOT RECRUITING

Royal Marsden Hospital (Sutton)

Sutton, SM2 5PT, United Kingdom

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms; Microsatellite Instability

Interventions

pembrolizumab; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Genomic Instability; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Clinical Trials

  Vividion Therapeutics

  STUDY DIRECTOR

Central Study Contacts

Vividion Clinical Trial Call Center

CONTACT

1+ 858-345-9752 (U.S. Only); clinicaltrials@vividion.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is an open label study. Participants will be assigned to dose cohorts in the order in which they are enrolled. However, if two or more cohorts in the same part of the study are open for enrollment at the same time, participants will be randomized into these cohorts.

Study Record Dates

• First Submitted: August 16, 2023
• First Posted: August 22, 2023
• Study Start: January 25, 2024
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027
• Last Updated: July 23, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2); US (14); MY (1); KR (7); GB (3); DK (1); BE (1); AU (2); CA (2); ES (5)