A Study of PRT7732, an Oral SMARCA2 Degrader, in Patients With Advanced or Metastatic Solid Tumors With a SMARCA4 Mutation

Phase 1TerminatedNCT06560645

Prelude Therapeutics42 enrolled

Overview

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.

This is an open-label, multi-center, first-in-human, Phase 1 study to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of PRT7732 an oral SMARCA degrader in patients with select advanced or metastatic solid tumors with a SMARCA4 mutation. Approximately 104 participants will be enrolled.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Advanced Solid Tumor Metastatic Solid Tumor Non-small Cell Lung Carcinoma SMARCA4 Mutation

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations (including contraception requirements), and other study procedures * Histologically confirmed advanced, recurrent, or metastatic solid tumor malignancy with any mutation of SMARCA4 by local testing that has either progressed on or is ineligible for standard of care therapy * Must have measurable or non-measurable (but evaluable) disease per RECIST v1.1 * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Willing to provide either archival or fresh tumor tissue sample * Adequate organ function (hematology, renal, and hepatic) Exclusion Criteria: * Participants with solid tumors with known concomitant SMARCA2 mutation or loss of protein expression * Clinically significant or uncontrolled cardiac disease, uncontrolled electrolyte disorders, uncontrolled or symptomatic central nervous system (CNS) metastases or leptomeningeal disease * History of other malignancy within 3 years except for adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, prostate adenocarcinoma with Gleason score of 3+3 or less, carcinoma in situ of the cervix, or other non-invasive or indolent malignancies, or malignancies previously treated with curative intent and not on active therapy or expected to require treatment or recurrence during the study * Receipt of any targeted therapy directed against BRM/BRG1 (SMARCA2/SMARCA4).

Locations (28)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Brigitte Harris Cancer Pavilion

Detroit, Michigan, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Memorial Sloan Kettering Cancer Center - Main Campus

New York, New York, United States

UNC Hospitals, The University of North Carolina Chapel Hill

Chapel Hill, North Carolina, United States

Outcomes

Primary Outcomes

Dose Limiting toxicity (DLT) of PRT7732

Incidence of dose limiting toxicities for patients in the dose escalation phase

Time frame: 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

Time frame: 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