RecruitingPhase 1

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 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)

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years and older
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests VVD-133214, a pill, alone or with bevacizumab or pembrolizumab in people with advanced solid tumors. Their tumors must have MSI or dMMR, changes linked to problems fixing damaged DNA. Researchers will check safety, how the body handles the drug, and whether it may slow cancer growth.

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Be fully active or able to do light work, even if heavy activity is limited.
  • Have a solid tumor confirmed by tissue or cell testing, with MSI or dMMR. The cancer must have spread or cannot be removed by surgery.
  • For VVD-133214 alone: Have tried at least 2 standard treatments for advanced cancer that stopped working or caused side effects you could not tolerate.
  • For VVD-133214 with bevacizumab: Have advanced colon or rectal cancer and 2 to 3 prior drug treatment plans. The last must have stopped working or caused side effects you could not tolerate. Certain prior drugs are required unless you could not receive or tolerate them.
  • For VVD-133214 with pembrolizumab: Have confirmed advanced colon or rectal cancer that cannot be treated with surgery. You must not have had drug treatment for cancer that has spread to distant sites.
  • Have cancer that can be measured on scans and be expected to live at least 12 weeks.
  • Have a stored tumor sample available, or be able to safely have a biopsy to collect one.
  • Have blood counts and organ and heart function that meet study rules.

Who can't join

  • Cannot or will not swallow pills; have trouble absorbing medicine through the gut; or have an allergy or intolerance to ingredients in the study drug.
  • Have uncontrolled cancer spread to the brain or spinal cord, or cancer in their lining.
  • Have an active or uncontrolled infection, certain recent serious infections, or a positive screening test for hepatitis B, hepatitis C, or HIV. Nail fungus is allowed.
  • Have uncontrolled diabetes or high blood sugar with symptoms; serious heart, blood vessel, or brain blood vessel disease within 6 months; or alcohol or drug abuse or dependence.
  • Have Werner syndrome, have taken a drug that blocks the WRN protein, or have used certain medicines that affect drug levels within 14 days before treatment.
  • Are pregnant, breastfeeding, or planning to become pregnant during the study.
  • For bevacizumab: Had major surgery within 4 weeks, or a deep vein or lung blood clot within 12 weeks; have a clotting disorder that raises bleeding risk; or have too much protein in urine, with an exception based on a 24-hour urine test.
  • For pembrolizumab: Have or had a disease where the immune system attacks the body, or a weak immune system, with some exceptions; have a history of lung inflammation or scarring; used medicines that weaken the immune system within 2 weeks, with some exceptions; or received an organ or tissue transplant.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

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 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 * 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 sites (16)

AZ

CA

GA

IL

KY

MI

NC

NJ

OK

TN

TX

UT