PRT3789 Monotherapy and in Combo w/Docetaxel in Participants w/Advanced or Metastatic Solid Tumors w/SMARCA4 Mutation

Prelude Therapeutics135 enrolled

Overview

This is a Phase 1 dose-escalation study of PRT3789, a SMARCA2 degrader, in participants with advanced or metastatic solid tumors with loss of SMARCA4 due to truncating mutation and/or deletion. The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) of PRT3789 monotherapy and in combination with docetaxel, describe any dose limiting toxicities (DLTs), define the dosing schedule, and to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) to be used in subsequent development of PRT3789.

This is an open-label, multi-center, dose-escalation, first in human, Phase 1 study of PRT3789 as monotherapy and in combination with docetaxel, a SMARCA2 degrader, evaluating participants with advanced or metastatic solid tumors with loss of SMARCA4 due to truncating mutation and/or deletion. The study will evaluate escalating doses of PRT3789 until the MTD or RP2D is determined. Taking into account pharmacokinetic and pharmacodynamic data from the preceding dose levels, the dose may be escalated until a dose limiting toxicity is identified. Approximately 186 participants will be enrolled in monotherapy, dose escalation, backfill, and combination cohorts.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

135

Conditions

Advanced Solid Tumor Metastatic Solid Tumor

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 (dose escalation and combination cohorts) and loss of function mutation of SMARCA4 (backfill cohorts) by local testing that have either progress on or ineligible for standard of care therapy * Must have measurable or non-measureable (but evaluable) disease per RECIST v1.1 for dose escalation and combination cohorts * Must have measureable diseases per RECIST v1.1 for backfill cohort * 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 another malignancy within 3 years except for adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive 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 * Concurrent treatment with strong or moderate CYP3A4 inhibitor or inducer

Locations (32)

University of California, Davis Comprehensive Cancer Center

Sacramento, California, United States

UCLA Hematology/Oncology - Santa Monica

Santa Monica, California, United States

Smilow Cancer Hospital Phase 1 Unit

New Haven, Connecticut, United States

AdventHealth Medical Group Oncology Research at Celebration

Celebration, Florida, United States

Mayo Clinic, Jacksonville

Jacksonville, Florida, United States

Outcomes

Primary Outcomes

Dose limiting toxicity (DLT) of PRT3789 monotherapy and in combination with docetaxel

Dose limiting toxicities will be evaluated over the 21-day observation period

Time frame: Baseline through Day 21

Safety and tolerability of PRT3789 monotherapy and in combination with docetaxel: AEs, CTCAE Assessments

Safety and tolerability will be evaluated by incidence of DLTs, laboratory measurements, dose interruption, modification, and discontinuation due to adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)