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 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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
295
VVD-133214 will be administered orally and once daily (QD) in 3-week cycles.
Pembrolizumab will be administered by intravenous (IV) infusion at a fixed dose of 200 mg on Day 1 of each 21-day cycle.
City of Hope Cancer Center
Duarte, California, United States
ACTIVE_NOT_RECRUITINGCity of Hope - Santa Clarita
Valencia, California, United States
RECRUITINGNorton Cancer Institute - MDC
Louisville, Kentucky, United States
ACTIVE_NOT_RECRUITINGDuke University
Durham, North Carolina, United States
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 pembrolizumab
Incidence of Dose-Limiting Toxicities
Time frame: Cycle 1 (1 cycle is 3 weeks)
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)
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Oklahoma University Health Sciences Center
Oklahoma City, Oklahoma, United States
ACTIVE_NOT_RECRUITINGSCRI Oncology Partners
Nashville, Tennessee, United States
ACTIVE_NOT_RECRUITINGMD Anderson Cancer Center
Houston, Texas, United States
ACTIVE_NOT_RECRUITINGAlfred Hospital
Melbourne, Victoria, Australia
ACTIVE_NOT_RECRUITINGUZ Leuven Gasthuisberg
Leuven, Belgium
ACTIVE_NOT_RECRUITINGBCCA-Vancouver Cancer Centre
Vancouver, British Columbia, Canada
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