A Study of PRT7732, an Oral SMARCA2 Degrader, in Patients With Advanced or Metastatic Solid Tumors With a SMARCA4 Mutation
NCT Number: NCT06560645
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Advanced Solid Tumor|Metastatic Solid Tumor|Non-small Cell Lung Carcinoma|SMARCA4 Mutation
Interventions: DRUG: PRT7732
Sponsor: Prelude Therapeutics
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 104
Study Design: Allocation: NA|Intervention Model: SEQUENTIAL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09
Completion Date: 2027-04
Locations: The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, United States

Summary:
This is a Phase 1 study to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of PRT7732 in patients with select advanced or metastatic solid tumors with a SMARCA4 mutation.

Primary Outcome Measures: Dose Limiting toxicity (DLT) of PRT7732, Incidence of dose limiting toxicities for patients in the dose escalation phase, Baseline through Day 21|Safety and tolerability of PRT7732 as measured by incidence of DLTs, Safety and tolerability will be evaluated by incidence of DLTs, Baseline through completion of study, an average of 2 years|Safety and tolerability of PRT7732 as measured by incidence of laboratory deviations, Safety and tolerability will be evaluated by laboratory measurements, Baseline through study completion, an average of 2 years|Safety and tolerability as measured by rates of dose modification due to AEs according to NCI CTCAE, Safety and tolerability will be evaluated by dose interruption, modification, and discontinuation due to adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Baseline through study completion, an average of 2 years|Maximum tolerated dose (MTD) of PRT7732, Maximum tolerated dose will be determined by the sponsor based on the Safety Review Committee's recommendation considering the totality of the available clinical safety, clinical efficacy, pharmacokinetics (PK), and pharmacodynamic data, Baseline through study completion, an average of 2 years|Recommended dose for expansion (RDE) of PRT7732, The RDE will be determined by the sponsor based on the Safety Review Committee's recommendation considering the totality of the available clinical safety, clinical efficacy, pharmacokinetics (PK), and pharmacodynamic data, Baseline through study completion, an average of 2 years
Secondary Outcome Measures: Efficacy of PRT7732, Best overall response of either complete response (CR) or partial response (PR), as assessed by the investigator per RECIST v1.1, Baseline through study completion, an average of 2 years|Pharmacokinetic profile of PRT7732 as a single agent: Maximum observed plasma concentration, Pharmacokinetics will be calculated including the maximum observed plasma concentration, Baseline through study completion, an average of 2 years|Pharmacokinetic profile of PRT7732 as a single agent: Area under the curve, Pharmacokinetics will be calculated including the area under the plasma concentration versus time curve (AUC), Baseline through study completion, an average of 2 years|Pharmacokinetic profile of PRT7732 as a single agent: Time of maximum concentration (Tmax) and half-life (T1/2), Pharmacokinetic parameters will be calculated using standard non-compartmental techniques, Baseline through study completion, an average of 2 years|Pharmacodynamic effects of PRT7732 as a single agent, The pharmacodynamic effect of PRT7732 demonstrating target engagement by assessment of SMARCA2 protein in peripheral blood mononuclear cells and tumor tissue as assessed by reduction in protein levels of SMARCA2 in peripheral blood mononuclear cells and/or tumor tissue, Baseline through study completion, an average of 2 years