Back to Trials
NCT06004245PHASE1Recruiting

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

Vividion Therapeutics, Inc.

Start Date

1/25/2024

Completion Date

5/31/2027

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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

Interventions

DRUG

VVD-133214

DRUG

Pembrolizumab

DRUG

Bevacizumab

Interested in This Trial?

Contact the trial locations directly using the information below to learn more about enrollment.

Expressing interest lets you review the study and consent before we connect you with the research site.

Conditions

Advanced Solid TumorsColorectal Cancer

Locations

City of Hope Cancer Center

Duarte, California 91010

United States

City of Hope at Irvine Lennar

Irvine, California 91355

United States

START Los Angeles

Los Angeles, California 90025

United States

Emory University School of Medicine

Atlanta, Georgia 30322

United States

Norton Cancer Institute - MDC

Louisville, Kentucky 40202

United States

University of Michigan

Ann Arbor, Michigan 48109

United States

START Midwest

Grand Rapids, Michigan 49546

United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey 08901

United States

Duke University

Durham, North Carolina 27705

United States

Oklahoma University Health Sciences Center

Oklahoma City, Oklahoma 73170

United States

SCRI Oncology Partners

Nashville, Tennessee 37203

United States

MD Anderson Cancer Center

Houston, Texas 77030

United States

START San Antonio

San Antonio, Texas 78229

United States

START Mountain Region

West Valley City, Utah 84119

United States

St Vincents Sydney

Darlinghurst, New South Wales 2010

Australia

Alfred Hospital

Melbourne, Victoria 3181

Australia

UZ Leuven Gasthuisberg

Leuven, 3000

Belgium

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia V5Z 4E6

Canada

Princess Margaret Cancer Center

Toronto, Ontario M5G 2M9

Canada

Rigshospitalet

København Ø, 2100

Denmark

CLCC Leon Berard Lyon

Lyon, 69008

France

Gustave Roussy

Villejuif, 94805

France

Sarawak Public Hospital

Kuching, Sarawak 93586

Malaysia

Kyungpook National University Chilgok Hospital

Daegu, 41404

South Korea

National Cancer Center

Gyeonggi-do, 10408

South Korea

Seoul National University Bundang Hospital

Seongnam-si, 13620

South Korea

Seoul National University Hospital

Seoul, 03080

South Korea

Asan Medical Center

Seoul, 05505

South Korea

Samsung Medical Center

Seoul, 06355

South Korea

Severance Hospital

Seoul, 33732

South Korea

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

Barcelona, BARCELONA 08035

Spain

Clinica Universidad de Navarra Madrid

Madrid, Madrid 28027

Spain

START Madrid. Centro Integral Oncologico Clara Campal

Madrid, Madrid 28050

Spain

Clinica Universitaria de Navarra

Pamplona, Navarre 31008

Spain

Hospital Clinico Universitario de Valencia

Valencia, Valencia 46010

Spain

Sarah Cannon Research Institute

London, W1G 6AD

United Kingdom

The Christie

Manchester, M20 4BX

United Kingdom

Royal Marsden Hospital (Sutton)

Sutton, SM2 5PT

United Kingdom