This is a Phase 1 dose-escalation and confirmation study of PRT2527, a Cyclin-dependent Kinase 9 (CDK9) inhibitor, in participants with advanced solid tumors. The purpose of this study is to define the dosing schedule, and maximally tolerated dose to be used in subsequent development of PRT2527.
This is a multicenter, open-label, dose-escalation and confirmation Phase 1 study of PRT2527, a CDK9 inhibitor, evaluating participants with selected advanced/metastatic sarcomas displaying a documented gene fusion, castrate resistant prostate cancer, hormone receptor positive HER2-negative breast cancer, advanced/metastatic non-small cell lung cancer, and solid tumors displaying MYC amplification. The study plan expects to evaluate approximately six dose levels of approximately 1-6 participants per dose level; however additional and/or intermediate dose levels may be explored. Taking into account pharmacokinetic and pharmacodynamic data from the preceding dose levels, the dose may be escalated until a dose limiting toxicity is identified. The total sample size will be approximately 30 patients for MTD and RP2D determination.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
PRT2527 will be administered by intravenous infusion
Sarah Cannon Research Institute at HealthONE
Denver, Colorado, United States
Investigational Drug Services, AdventHealth Celebration
Celebration, Florida, United States
Florida Cancer Specialists
Sarasota, Florida, United States
Memorial Sloan Kettering Cancer Center
Dose limiting toxicities (DLT) of PRT2527
Dose limiting toxicities will be evaluated over the 21-day observation period
Time frame: Baseline through Day 21
Maximally tolerated dose (MTD) of PRT2527
The MTD will be established for further investigation in participants with advanced solid tumors
Time frame: Baseline through approximately 1 year
Recommended phase 2 dose (RP2D) and schedule of PRT2527
The RP2D will be established for further investigation in participants with advanced solid tumors
Time frame: Baseline through approximately 1 year
Safety and tolerability of PRT2527: AEs, SAEs, CTCAE assessments
Safety and tolerability will be assessed by recording adverse events (AEs) and serious adverse events (SAEs) according to Common Terminology Criteria for Adverse Events (CTCAE)
Time frame: Baseline through approximately 2 years
Pharmacokinetic profile of PRT2527: maximum observed plasma concentration
PRT2527 pharmacokinetics will be calculated including the maximum observed plasma concentration
Time frame: Baseline through approximately 1 year
Anti-tumor activity of PRT2527: measurement of objective responses
Anti-tumor activity of PRT2527 based on the measurement of objective responses to PRT2527 according to the disease-specific response criteria for patients with advanced solid tumors
Time frame: Baseline through approximately 2 years
Duration of response to PRT2527: Objective responses
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New York, New York, United States
Thomas Jefferson University, Sidney Kimmel Cancer Center
Philadelphia, Pennsylvania, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
Mary Crowley Cancer Research
Dallas, Texas, United States
NEXT Virginia
Fairfax, Virginia, United States
Duration of response will be calculated for all patients eligible for response determination from the time that a response is first observed until progression or death, whichever occurs first
Time frame: Baseline through approximately 2 years