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.

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