Recruiting

Phase 1

RO7589831 & PembrolizumabA 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.

Code:

NCT06004245

Conditions

Advanced Solid Tumors

Colorectal Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

VVD-133214

Pembrolizumab

Bevacizumab

Study Details

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

Advanced Solid Tumors

Colorectal Cancer

Study ID

NCT06004245

Start date

Jan 25, 2024

Status verified date

Jul, 2026

Completion date

May 31, 2027

Anticipated

Primary completion date

May 31, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

280 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: VVD-133214 Dose Escalation

experimental: VVD-133214 Monotherapy Expansion

experimental: VVD-133214 + Pembrolizumab Expansion

experimental: VVD-133214 + Bevacizumab Expansion

Interventions

VVD-133214

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

Pembrolizumab

Pembrolizumab will be administered by intravenous (IV) infusion at a fixed dose of 200 mg on Day 1 of each 21-day cycle.

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.

Primary outcome measure

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) [ Time Frame: 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 [ Time Frame: Cycle 1 (1 cycle is 3 weeks) ]

Central Contacts and Locations

Central contacts

Vividion Clinical Trial Call Center

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

Locations

City of Hope Cancer Center

Recruiting

Duarte, California, United States, 91010

City of Hope at Irvine Lennar

Recruiting

Irvine, California, United States, 91355

START Los Angeles

Recruiting

Los Angeles, California, United States, 90025

Contacts

Vividion Clinical Trial Call Center Study Director

+1 8583459752 clinicaltrials@vividion.com

Emory University School of Medicine

Recruiting

Atlanta, Georgia, United States, 30322

Contacts

Vividion Clinical Trial Call Center

+1 8583459752 clinicaltrials@vividion.com

Norton Cancer Institute - MDC

Recruiting

Louisville, Kentucky, United States, 40202

University of Michigan

Recruiting

Ann Arbor, Michigan, United States, 48109

Contacts

Vividion Clinical Trial Call Center Study Director

+1 8583459752 clinicaltrials@vividion.com

START Midwest

Recruiting

Grand Rapids, Michigan, United States, 49546

Contacts

Vividion Clinical Trial Call Center Study Director

+1 8583459752 clinicaltrials@vividion.com

Rutgers Cancer Institute of New Jersey

Recruiting

New Brunswick, New Jersey, United States, 08901

Contacts

Vividion Clinical Trial Call Center

+1 8583459752 clinicaltrials@vividion.com

Oklahoma University Health Sciences Center

Recruiting

Oklahoma City, Oklahoma, United States, 73170

SCRI Oncology Partners

Recruiting

Nashville, Tennessee, United States, 37203

MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

START San Antonio

Recruiting

San Antonio, Texas, United States, 78229

Contacts

Vividion Clinical Trial Call Center Study Director

+1 8583459752 clinicaltrials@vividion.com

START Mountain Region

Recruiting

West Valley City, Utah, United States, 84119

Contacts

Vividion Clinical Trial Call Center Study Director

+1 8583459752 clinicaltrials@vividion.com

Princess Margaret Cancer Center

Recruiting

Toronto, Ontario, Canada, M5G 2M9

More Information

Sponsor

Vividion Therapeutics, Inc.

Last update posted

Aug 17, 2026

Last verified

Jul, 2026

Keywords

Deficient mismatch repair
dMMR
Microsatellite instability
MSI

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Vividion Therapeutics, Inc. on 2026-08-17.