A Phase 2 interventional study of VVD-133214 and Pembrolizumab in Colorectal Adenocarcinoma, sponsored by Vividion Therapeutics, Inc.. Recruiting at 122 sites in 22 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-21.
Sponsored by Vividion Therapeutics, Inc. (part of Bayer) · Phase 2, Interventional, and Treatment
Researchers are looking for a better way to treat people with advanced colorectal cancer.
Colorectal cancer (cancer of the colon or rectum) is one of the most common cancers worldwide. Treatments include surgery, chemotherapy, radiotherapy, and immunotherapy; however, these treatments do not work for everyone, may cause serious adverse events or may stop working eventually. New treatments and treatment combinations are needed, especially for cancers that cannot be removed with surgery or that have spread to other parts of the body (called advanced or metastatic cancer).
Cells normally repair themselves when mistakes happen as they divide. But in some people with cancer, the repair system does not work properly because of a problem called dMMR (deficient mismatch repair). As a result, mistakes build up in the cell's DNA, leading to a condition called MSI (microsatellite instability). Over time, these changes can cause cells to grow and behave abnormally, contributing to the development and growth of cancer.
To survive, some cancer cells with dMMR or MSI rely on a protein called Werner helicase. This protein helps repair some of the DNA damage allowing them to keep growing. Because these cancer cells depend more on Werner helicase than healthy cells, blocking this protein may help stop cancer cells from surviving while having less effect on healthy cells.
The study drug, VVD-133214, is designed to block the Werner helicase protein. Blocking this protein may help stop cancer cells from growing, while causing less harm to healthy cells. VVD-133214 is being studied in combination with pembrolizumab, an approved immunotherapy that helps the immune system recognize and attack cancer cells.
This study will test the combination of VVD-133214 and pembrolizumab in people with advanced colorectal cancer with MSI and/or dMMR who have not yet received treatment for their advanced disease. The study aims to find the best dose of VVD-133214 in combination with pembrolizumab and to test whether the combination is more effective than pembrolizumab alone.
Participants will receive treatment with VVD-133214 for as long as it can help them and does not cause serious adverse events. Treatment with pembrolizumab will stop after two years. Participants can also stop treatment at any time.
During the study, participants will have regular visits with the study doctor for tests, scans, and check-ups. These visits help check how well the cancer is responding to the treatment and monitor the participants' health.
The study will also monitor adverse events, which are any new or worsening medical problems that can happen during the study. Doctors record all adverse events, irrespective of whether the study doctor believes they are related to the study treatments, to help ensure participants' safety throughout the study.
After stopping treatment, participants will return for follow-up visits: 30 days after their last dose of VVD-133214 and/or 100 days after their last dose of pembrolizumab. After that, participants will have long-term follow-up visits every 90 days for as long as they agree to continue participating in follow-up.
145 studies on the registry are indexed under Colorectal Neoplasms, Hereditary Nonpolyposis; 59 are open to participants now.
This study's planned enrollment of 140 is below the median of 200 across 75 interventional studies indexed under Colorectal Neoplasms, Hereditary Nonpolyposis.
Browse Colorectal Neoplasms, Hereditary Nonpolyposis studies →Vividion Therapeutics, Inc. is the lead sponsor of 5 studies on the registry; 4 are open to participants now.
First submitted after Vividion Therapeutics, Inc. became part of Bayer.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adjuvant and neoadjuvant
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
PD-1, PD-L1 and checkpoint inhibitors
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants will receive VVD-133214 in combination with pembrolizumab
Drug: VVD-133214 · Drug: Pembrolizumab
Participants will receive VVD-133214 in combination with pembrolizumab
Drug: VVD-133214 · Drug: Pembrolizumab
Participants will receive pembrolizumab only (monotherapy)
Drug: Pembrolizumab
VVD-133214 will be administered orally
Pembrolizumab will be administered by intravenous infusion (IV) every three weeks
Landmark progression-free survival (PFS) rate at 6 months, as assessed by the investigator
Defined as the proportion of participants who are alive and free from disease progression as per RECIST v1.1
Time frame: From start of study treatment until end of follow-up (up to approximately 36 months)
Incidence and severity of Adverse Events (AEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0)
Time frame: From start of study treatment up to 30 days following the last dose of study drug (100 days after last administration of pembrolizumab)
Recommended Phase 2 Dose (RP2D) of VVD-133214 in combination with pembrolizumab
The RP2D will be based on incidence, severity and frequency of adverse events, anti-tumor activity, PK/PD, and assessment of disease biomarkers for two doses of VVD-133214 combined with the standard of care (SoC) dose of pembrolizumab
Time frame: From start of study treatment until end of follow-up (up to approximately 36 months)
Maximum plasma concentration observed (Cmax) following single and multiple doses of VVD-133214
Time frame: Predose and multiple timepoints post-dose, up to approximately 36 months
Time of maximum plasma concentration observed (Tmax) following single and multiple doses of VVD-133214
Time frame: Predose and multiple timepoints post-dose, up to approximately 36 months
Area under the plasma concentration-time curve (AUC) following single and multiple doses of VVD-133214
Time frame: Predose and multiple timepoints post-dose, up to approximately 36 months
Overall response rate (ORR) according to RECIST v1.1 as assessed by the Investigator
Time frame: From start of study treatment until end of follow-up (up to approximately 36 months)
Disease control rate (DCR) according to RECIST v1.1 as assessed by the Investigator
Time frame: From start of study treatment until end of follow-up (up to approximately 36 months)
Duration of response (DOR) according to RECIST v1.1 as assessed by the Investigator
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)
Median progression-free survival (mPFS) according to RECIST v1.1 as assessed by the Investigator
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)
Showing the first 100 of 122 sites across 22 countries. Choose a country and city above to see the rest.
Plan to share: No — Currently, there is no established plan for the sharing of Individual Patient Data (IPD) from this study. The availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA 'Principles for responsible clinical trial data sharing.' This pertains to the scope, timepoint, and process of data access. As such, Bayer commits to considering requests from qualified researchers for patient- / study-level clinical trial data, and documents from clinical trials involving medicines and indications approved in the US and EU. However, this commitment does not reflect an active IPD sharing plan. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Researchers can use www.vivli.org to request access to IPD and documents from clinical studies to conduct research. Information on Bayer's criteria for listing studies is provided in the member section of the portal.
No publications or documents are linked to this record.
Started Sep 2026 (actual). Primary completion is estimated for Jun 2028, 21 months after the start.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
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Colorectal Neoplasms, Hereditary Nonpolyposis →