This is a Phase 1 dose-escalation study of PRT3645, a Cyclin-dependent Kinase 4/6 (CDK4/6) inhibitor, in patients with advanced or metastatic solid tumors. The purpose of this study is to investigate the safety, tolerability, dose limiting toxicity, and to determine maximally tolerated dose and recommended phase 2 dose to be used in subsequent development of PRT3645.
This is an open-label, multicenter, dose-escalation Phase 1 study of PRT3645, a CDK4/6 inhibitor, evaluating patients with selected advanced or metastatic solid tumors including breast cancer (BC), glioblastoma (GBM), non-small cell lung cancer (NSCLC), sarcomas, head and neck squamous cell carcinoma (HNSCC), malignant mesothelioma, and endometrial cancer. The study plan expects to evaluate approximately eight dose levels however additional 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. Up to 15 patients may be enrolled at a dose shown to be tolerated for confirmation of the MTD and/or RP2D.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
22
PRT3645 capsules will be self-administered once daily, continuously, at the dose-level assigned
Smilow Cancer Hospital Phase 1 Unit
New Haven, Connecticut, United States
AdventHealth Medical Group Oncology Research at Celebration
Celebration, Florida, United States
Miami Cancer Institute
Miami, Florida, United States
Florida Cancer Specialists
Sarasota, Florida, United States
Winship Cancer Institute, Emory University
Atlanta, Georgia, United States
Laura and Isaac Perlmutter Cancer Center/ NYU Langone Health
New York, New York, United States
Cleveland Clinic
Cleveland, Ohio, United States
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
Thomas Jefferson University, Sidney Kimmel Cancer Center
Philadelphia, Pennsylvania, United States
Tennessee Oncology, PLLC
Nashville, Tennessee, United States
...and 3 more locations
Dose limiting toxicity (DLT) of PRT3645
Dose limiting toxicity will be evaluated over the 28-day observation period
Time frame: Baseline through Day 28
Safety and tolerability of PRT3645: AEs, CTCAE Assessments
Safety and tolerability will be evaluated by incidence of DLTs, laboratory measurements, severity of adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.
Time frame: Baseline through approximately 2 years
Maximally tolerated dose (MTD)/Recommended phase 2 dose (RP2D) of PRT3645
The MTD/RP2D will be established for further investigation in participants with advanced solid tumors
Time frame: Baseline through approximately 2 years
Efficacy of PRT3645: Tumor assessment and responses
Objective response rate (ORR), Progression-free survival (PFS), Disease control rate (DCR) and Duration of response (DOR) will use RECIST v1.1, mRECIST v1.1, and/or RANO as primary measure for tumor assessment and response.
Time frame: Baseline through approximately 2 years
Pharmacokinetic profile of PRT3645: Minimum and maximum observed plasma concentration
PRT3645 pharmacokinetics will be calculated including the minimum and maximum observed plasma concentration.
Time frame: Baseline through approximately 2 years
Pharmacodynamic effect of PRT3645: Target engagement
Pharmacodynamic effect of PRT3645 demonstrating target engagement by assessment of phosphorylation of Rb.
Time frame: Baseline through approximately 2 years
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