Advanced Solid TumorsPhase 1NCT06004245
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 1 study testing VVD-133214, Pembrolizumab and Bevacizumab in people with Advanced Solid Tumors and Colorectal Cancer, run by Vividion Therapeutics, Inc. at 55 sites in 11 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors, Colorectal Cancer
- What is being tested?
- VVD-133214, Pembrolizumab and Bevacizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 280 participants
- Where
- 55 sitesin 11 countries
- Study dates
- 25 Jan 2024to 31 May 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 monotherapy only (solid tumor): Have received and then progressed following or are intolerant to at least 2 standard treatment regimens in the advanced setting including standard chemotherapy or checkpoint inhibitors according to tumor type.
- 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 and demonstrated progressive disease or intolerance to the last regimen. Prior treatment regimens must have included (unless not eligible for or intolerant to any of these agents): An immune checkpoint inhibitor (if available as standard of care), Fluoropyrimidine, Irinotecan and/or oxaliplatin, +/- an anti-VEGF monoclonal antibody, Participants with RAS WT tumors may have received anti-epidermal growth factor receptor (EGFR) monoclonal antibody based on Investigator discretion. Treatment with adjuvant/neoadjuvant chemotherapy and/or immunotherapy will count as a line of therapy for advanced disease if progression occurred during or within 12 months of completing the treatment.
- 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.
- Presence of measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
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- 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
Who cannot join
- 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
Show all 24Show fewer
- 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
Trial locations and contacts
55 sites in 11 countries. Contact the study team or a site near you to ask about taking part.
55 sites in 11 countries
United States18 sites, 16 recruiting
- Recruiting
University of Michigan
Ann Arbor, Michigan, 48109
Vividion Clinical Trial Call Center Study Director, +1 8583459752, clinicaltrials@vividion.com
- Recruiting
Emory University School of Medicine
Atlanta, Georgia, 30322
Vividion Clinical Trial Call Center, +1 8583459752, clinicaltrials@vividion.com
- Not yet recruiting
University of Chicago
Chicago, Illinois, 60637
Vividion Clinical Trial Call Center Study Director, +1 8583459752, clinicaltrials@vividion.com
- Recruiting
City of Hope Cancer Center
Duarte, California, 91010
- Completed
Duke University
Durham, North Carolina, 27705
- Recruiting
START Midwest
Grand Rapids, Michigan, 49546
Vividion Clinical Trial Call Center Study Director, +1 8583459752, clinicaltrials@vividion.com
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
- Recruiting
City of Hope at Irvine Lennar
Irvine, California, 91355
- Recruiting
START Los Angeles
Los Angeles, California, 90025
Vividion Clinical Trial Call Center Study Director, +1 8583459752, clinicaltrials@vividion.com
- Not yet recruiting
The Angeles Clinic and Research Institute
Los Angeles, California, 90025
Study Director, +1 8583459752, clinicaltrialcenters@vividion.com
- Recruiting
Norton Cancer Institute - MDC
Louisville, Kentucky, 40202
- Not yet recruiting
West Virginia University Cancer Institute
Morgantown, West Virginia, 26506
Study Director, +1 8583459752, clinicaltrialcenters@vividion.com
- Recruiting
SCRI Oncology Partners
Nashville, Tennessee, 37203
- Recruiting
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08901
Vividion Clinical Trial Call Center, +1 8583459752, clinicaltrials@vividion.com
- Completed
Oklahoma University Health Sciences Center
Oklahoma City, Oklahoma, 73170
- Recruiting
START San Antonio
San Antonio, Texas, 78229
Vividion Clinical Trial Call Center Study Director, +1 8583459752, clinicaltrials@vividion.com
- Not yet recruiting
University of Arizona Cancer Center
Tucson, Arizona, 85719
Vividion Clinical Trial Call Center Study Director, +1 8583459752, clinicaltrials@vividion.com
- Recruiting
START Mountain Region
West Valley City, Utah, 84119
Vividion Clinical Trial Call Center Study Director, +1 8583459752, clinicaltrials@vividion.com
Spain9 sites, 9 recruiting
- Recruiting
Vall d'Hebron Institute of Oncology (VHIO), Barcelona
Barcelona, BARCELONA, 08035
- Not yet recruiting
NEXT Oncology - Barcelona
Barcelona, 08023
Vividion Clinical Trial Call Center Study Director, +1 8583459752, clinicaltrials@vividion.com
- Not yet recruiting
START Barcelona
Barcelona, 08023
Vividion Clinical Trial Call Center Study Director, +1 8583459752, clinicaltrials@vividion.com
- Recruiting
Clinica Universidad de Navarra Madrid
Madrid, Madrid, 28027
- Recruiting
START Madrid. Centro Integral Oncologico Clara Campal
Madrid, Madrid, 28050
- Not yet recruiting
Start Madrid-FJD, Hospital Fundacion Jimenez Diaz
Madrid, 28040
Vividion Clinical Trial Call Center Study Director, +1 8583459752, clinicaltrials@vividion.com
- Not yet recruiting
NEXT Oncology-Hospital Universitario Quironsalud Madrid
Madrid, 28223
Vividion Clinical Trial Call Center Study Director, +1 8583459752, clinicaltrials@vividion.com
- Recruiting
Clinica Universitaria de Navarra
Pamplona, Navarre, 31008
- Recruiting
Hospital Clinico Universitario de Valencia
Valencia, Valencia, 46010
South Korea7 sites, 7 recruiting
- Recruiting
Kyungpook National University Chilgok Hospital
Daegu, 41404
Vividion Clinical Trial Call Center Study Director, +1 8583459752, clinicaltrials@vividion.com
- Recruiting
National Cancer Center
Gyeonggi-do, 10408
Vividion Clinical Trial Call Center Study Director, +1 8583459752, clinicaltrials@vividion.com
- Recruiting
Seoul National University Bundang Hospital
Seongnam-si, 13620
Vividion Clinical Trial Call Center Study Director, +1 8583459752, clinicaltrials@vividion.com
- Recruiting
Seoul National University Hospital
Seoul, 03080
Vividion Clinical Trial Call Center Study Director, +1 8583459752, clinicaltrials@vividion.com
- Recruiting
Asan Medical Center
Seoul, 05505
Vividion Clinical Trial Call Center Study Director, +1 8583459752, clinicaltrials@vividion.com
- Recruiting
Samsung Medical Center
Seoul, 06355
Vividion Clinical Trial Call Center Study Director, +1 8583459752, clinicaltrials@vividion.com
- Recruiting
Severance Hospital
Seoul, 33732
Vividion Clinical Trial Call Center Study Director, +1 8583459752, clinicaltrials@vividion.com
France6 sites, 5 recruiting
- Completed
CLCC Leon Berard Lyon
Lyon, 69008
- Not yet recruiting
Institut regional du Cancer de Montpellier
Montpellier, 34298
Study Director, +1 8583459752, clinicaltrialcenters@vividion.com
- Not yet recruiting
Hôpital saint Antoine
Paris, 75012
Study Director, +1 8583459752, clinicaltrialcenters@vividion.com
- Not yet recruiting
Hopital europeen Georges Pompidou
Paris, 75015
Study Director, +1 8583459752, clinicaltrialcenters@vividion.com
- Not yet recruiting
Oncopole Claudius Regaud
Toulouse, 31059
Study Director, +1 8583459752, clinicaltrialcenters@vividion.com
- Recruiting
Gustave Roussy
Villejuif, 94805
Belgium3 sites, 3 recruiting
- Not yet recruiting
Cliniques universitaires de Saint Luc
Brussels, 12000
Vividion Clinical Trial Call Center Study Director, +1 8583459752, clinicaltrialcenters@vividion.com
- Not yet recruiting
UZ Leuven Gasthuisberg
Ghent, 3000
Study Director, +1 8583459752, clinicaltrialcenters@vividion.com
- Not yet recruiting
UZ Gent
Ghent, 9000
Study Director, +1 8583459752, clinicaltrialcenters@vividion.com
China3 sites, 3 recruiting
- Recruiting
Beijing Cancer Hospital
Beijing, 100142
Vividion Clinical Trial Call Center Study Director, +1 8583459752, clinicaltrials@vividion.com
- Recruiting
The Sixth Hospital, affiliated with Sun Yat-sen University
Guangzhou, 510655
Vividion Clinical Trial Call Center Study Director, +1 8583459752, clinicaltrials@vividion.com
- Recruiting
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, 310022
Vividion Clinical Trial Call Center Study Director, +1 8583459752, clinicaltrials@vividion.com
United Kingdom3 sites, 3 recruiting
- Recruiting
Sarah Cannon Research Institute
London, W1G 6AD
- Recruiting
The Christie
Manchester, M20 4BX
- Recruiting
Royal Marsden Hospital (Sutton)
Sutton, SM2 5PT
Australia2 sites, 2 recruiting
- Recruiting
St Vincents Sydney
Darlinghurst, New South Wales, 2010
Vividion Call Center, +1 8583459752, clinicaltrials@vividion.com
- Recruiting
Alfred Hospital
Melbourne, Victoria, 3181
Canada2 sites, 1 recruiting
- Recruiting
Princess Margaret Cancer Center
Toronto, Ontario, M5G 2M9
- Completed
BCCA-Vancouver Cancer Centre
Vancouver, British Columbia, V5Z 4E6
Malaysia1 site, 1 recruiting
- Recruiting
Sarawak Public Hospital
Kuching, Sarawak, 93586
Vividion Call Center, +1 8583459752, clinicaltrials@vividion.com
About this study
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)
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
- Being tested
- VVD-133214, Pembrolizumab, Bevacizumab
- Keywords
- Deficient mismatch repair, dMMR, Microsatellite instability, MSI
- Medical subject headings
- Colorectal Neoplasms, Microsatellite Instability
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VVD-133214Drug
VVD-133214 will be administered orally and once daily (QD) in 3-week cycles.
PembrolizumabDrug
Also called KEYTRUDA®
Pembrolizumab will be administered by intravenous (IV) infusion at a fixed dose of 200 mg on Day 1 of each 21-day cycle.
BevacizumabDrug
Also called Avastin
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.
| Study group | Role | What they receive |
|---|---|---|
| VVD-133214 Dose Escalation | Experimental | Not described Receives: Drug: VVD-133214 |
| VVD-133214 Monotherapy Expansion | Experimental | Not described Receives: Drug: VVD-133214 |
| VVD-133214 + Pembrolizumab Expansion | Experimental | Not described Receives: Drug: VVD-133214; Drug: Pembrolizumab |
| VVD-133214 + Bevacizumab Expansion | Experimental | Not described Receives: Drug: VVD-133214; Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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
Measured: Cycle 1 (1 cycle is 3 weeks)
Secondary outcomes (11)
Maximum Plasma Concentration Observed (Cmax) of VVD-133214
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Objective Response Rate
Measured: From start of study treatment until end of follow-up (up to approximately 36 months)
Disease Control Rate
Measured: From start of study treatment until end of follow-up (up to approximately 36 months)
Duration of Response
Measured: 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
Measured: 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
Measured: From start of study treatment to the time of death from any cause (up to approximately 36 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2023
- Study start25 Jan 2024
- Primary completion31 May 2027 (estimated)
- Study completion31 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 280 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vividion Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Vividion Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06004245
- Sponsor's protocol ID
- VVD-133214-01
- Other IDs
- 2023-503170-20-01, 2023
- Status last verified
- Oct 2026
- First submitted
- 16 Aug 2023
- Last updated
- 21 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Yap TA, Fontana E, Cook N, Fakih M, Bechter O, Tsang ES, Calvo E, Rohrberg KS, Ros J, Matos I, Strickler JH, Ameratunga M, Pelster M, Sharp A, Grewal J, Ulahannan S, Belani R, Patricelli MP, Blake SM, Dejardin D, Fowler S, Godfried Sie C, Heller A, Henkel N, Hettich M, Lahr A, Lamparter D, Lane C, Liu T, Meistermann H, Meille C, Parrott N, Sotiriou SK, Reeves D, Romagnoli B, Pettazzoni P, Waterkamp D, Wittwer M, Fu Y, Postel-Vinay S. Werner helicase inhibitor for advanced microsatellite instability solid tumors: a phase 1 trial. Nat Med. 2026 Sep 29. doi: 10.1038/s41591-026-04657-3. Online ahead of print.
PubMed 42811189
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT06004245
- Acronym / sponsor ID
- VVD-133214-01
- Conditions
- Advanced Solid Tumors, Colorectal Cancer
- Keywords
- Deficient mismatch repair, dMMR, Microsatellite instability, MSI
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 280 participants (estimated)
- Lead sponsor
- Vividion Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 25 Jan 2024 (actual)
- Primary completion
- 31 May 2027 (estimated)
- Study completion
- 31 May 2027 (estimated)
- First posted
- 22 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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 monotherapy only (solid tumor): Have received and then progressed following or are intolerant to at least 2 standard treatment regimens in the advanced setting including standard chemotherapy or checkpoint inhibitors according to tumor type.
- 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 and demonstrated progressive disease or intolerance to the last regimen. Prior treatment regimens must have included (unless not eligible for or intolerant to any of these agents): An immune checkpoint inhibitor (if available as standard of care), Fluoropyrimidine, Irinotecan and/or oxaliplatin, +/- an anti-VEGF monoclonal antibody, Participants with RAS WT tumors may have received anti-epidermal growth factor receptor (EGFR) monoclonal antibody based on Investigator discretion. Treatment with adjuvant/neoadjuvant chemotherapy and/or immunotherapy will count as a line of therapy for advanced disease if progression occurred during or within 12 months of completing the treatment.
- 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.
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VVD-133214VVD-133214 will be administered orally and once daily (QD) in 3-week cycles. | Drug | VVD-133214 + Bevacizumab Expansion, VVD-133214 + Pembrolizumab Expansion, VVD-133214 Dose Escalation, VVD-133214 Monotherapy Expansion |
| PembrolizumabAlso: KEYTRUDA®Pembrolizumab will be administered by intravenous (IV) infusion at a fixed dose of 200 mg on Day 1 of each 21-day cycle. | Drug | VVD-133214 + Pembrolizumab Expansion |
| BevacizumabAlso: AvastinBevacizumab will be administered by intravenous (IV) infusion at a fixed dose of 7.5 mg/kg on Day 1 of each 21-day cycle. | Drug | VVD-133214 + Bevacizumab Expansion |
Primary outcome
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)
11 secondary outcomes
Maximum Plasma Concentration Observed (Cmax) of VVD-133214
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Objective Response Rate
Time frame: From start of study treatment until end of follow-up (up to approximately 36 months)
Disease Control Rate
Time frame: From start of study treatment until end of follow-up (up to approximately 36 months)
Duration of Response
Time frame: 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
Time frame: 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
Time frame: From start of study treatment to the time of death from any cause (up to approximately 36 months)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2026.
- Derived from this study: PubMed 42811189Yap TA, Fontana E, Cook N, Fakih M, Bechter O, Tsang ES, Calvo E, Rohrberg KS, Ros J, Matos I, Strickler JH, Ameratunga M, Pelster M, Sharp A, Grewal J, Ulahannan S, Belani R, Patricelli MP, Blake SM, Dejardin D, Fowler S, Godfried Sie C, Heller A, Henkel N, Hettich M, Lahr A, Lamparter D, Lane C, Liu T, Meistermann H, Meille C, Parrott N, Sotiriou SK, Reeves D, Romagnoli B, Pettazzoni P, Waterkamp D, Wittwer M, Fu Y, Postel-Vinay S. Werner helicase inhibitor for advanced microsatellite instability solid tumors: a phase 1 trial. Nat Med. 2026 Sep 29. doi: 10.1038/s41591-026-04657-3. Online ahead of print.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Clinical Trials study director
Vividion Therapeutics
55 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing VVD-133214, Pembrolizumab and Bevacizumab in people with Advanced Solid Tumors and Colorectal Cancer, run by Vividion Therapeutics, Inc. at 55 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 55 sites in United States, Spain, South Korea, France, Belgium and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Vividion Clinical Trial Call Center (1+ 858-345-9752 (U.S. Only), clinicaltrials@vividion.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06004245, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2026.