A Study to Evaluate the Efficacy of VVD-133214 in Combination With Pembrolizumab Compared With Pembrolizumab Alone in Participants With Advanced Cancer of the Colon or Rectum

Conditions

• Colorectal Adenocarcinoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• VVD-133214 — DRUG
  VVD-133214 will be administered orally
• Pembrolizumab — DRUG
  Pembrolizumab will be administered by intravenous infusion (IV) every three weeks

Study Details

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.

Key Dates

First listed

Sep 9, 2026

Start date

Sep 15, 2026

Status verified

Sep 2026

Primary completion

Jun 30, 2028

Completion

Dec 31, 2030

Study Design

Enrollment

140 participants (estimated)

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: VVD-133214 Dose 1 + Pembrolizumab
  Participants will receive VVD-133214 in combination with pembrolizumab
• Experimental: VVD-133214 Dose 2 + Pembrolizumab
  Participants will receive VVD-133214 in combination with pembrolizumab
• Active Comparator: Pembrolizumab
  Participants will receive pembrolizumab only (monotherapy)

Primary Outcome Measure

Landmark progression-free survival (PFS) rate at 6 months, as assessed by the investigator [ Time Frame: From start of study treatment until end of follow-up (up to approximately 36 months) ]

Central Contacts

• Bayer Clinical Trials Contact
  18888422937
  [email protected]

Locations (4)

Find similar trials in Tucson, AZ

Related Studies

• Phase 1 Study of INBRX-109 in Subjects With Locally Advanced or Metastatic Solid Tumors Including Sarcomas
  PHASE1 · Recruiting · Inhibrx Biosciences, Inc · Beverly Hills, California
• Minimal Residual Disease Assessment in Patients With Colorectal Cancer, the MiRDA-C Study
  Recruiting · M.D. Anderson Cancer Center · Houston, Texas
• A Study to Evaluate the Safety and Efficacy of Mesothelin-Targeting Logic-gated CAR T, in Participants With Solid Tumors That Express MSLN and Have Lost HLA-A*02 Expression
  PHASE1/PHASE2 · Recruiting · A2 Biotherapeutics Inc. · Gilbert, Arizona
• A Study to Evaluate the Safety and Efficacy of A2B395, an Allogeneic Logic-gated CAR T, in Participants With Solid Tumors That Express EGFR and Have Lost HLA-A*02 Expression
  PHASE1/PHASE2 · Recruiting · A2 Biotherapeutics Inc. · Gilbert, Arizona