COMPLETED

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

Conditions

Advanced Solid Tumor Metastatic Solid Tumor Non-small Cell Lung Cancers SMARCA4 Gene Mutation Advanced Solid Tumors BRG1 BRM Metastatic Solid Tumors NSCLC PRT3789 SMARCA2 Degrader SMARCA4 Docetaxel

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Phase 1 Open-Label, Multi-Center, Safety and Efficacy Study of PRT3789 as Monotherapy and in Combination With Docetaxel in Participants With Advanced or Metastatic Solid Tumors With a SMARCA4 Mutation

Quick Facts

Study Start:2023-05-02

Study Completion:2025-10-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:COMPLETED

Study ID

NCT05639751

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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)	* 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

Inclusion Criteria

Exclusion 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)

* 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

Contacts and Locations

Study Locations (Sites)

University of California, Davis Comprehensive Cancer Center

Sacramento, California, 95817

United States

UCLA Hematology/Oncology - Santa Monica

Santa Monica, California, 90404

United States

Smilow Cancer Hospital Phase 1 Unit

New Haven, Connecticut, 06511

United States

AdventHealth Medical Group Oncology Research at Celebration

Celebration, Florida, 34747

United States

Mayo Clinic, Jacksonville

Jacksonville, Florida, 32224

United States

Winship Cancer Institute

Atlanta, Georgia, 30322

United States

Northwestern Memorial Hospital

Chicago, Illinois, 60611

United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287

United States

Massachusetts General Hospital

Boston, Massachusetts, 02114

United States

Dana Farber Cancer Institute

Boston, Massachusetts, 02215

United States

Mayo Clinic, Rochester

Rochester, Minnesota, 55905

United States

Washington University School of Medicine - Siteman Cancer Center

St Louis, Missouri, 63110

United States

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, 10016

United States

New York Presbyterian Hospital - Columbia University Medical Center

New York, New York, 10032

United States

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106

United States

Cleveland Clinic

Cleveland, Ohio, 44195

United States

Providence Cancer Institute Franz Clinic

Portland, Oregon, 97213

United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030

United States

NEXT Virginia

Fairfax, Virginia, 22031

United States

Collaborators and Investigators

Sponsor: Prelude Therapeutics

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-05-02

Study Completion Date2025-10-01

Study Record Updates

Study Start Date2023-05-02

Study Completion Date2025-10-01

Terms related to this study

Keywords Provided by Researchers

Advanced Solid Tumors
BRG1
BRM
Metastatic Solid Tumors
Non-Small Cell Lung Cancers
NSCLC
PRT3789
SMARCA2 Degrader
SMARCA4
Docetaxel

Additional Relevant MeSH Terms

Advanced Solid Tumor
Metastatic Solid Tumor
Non-small Cell Lung Cancers
SMARCA4 Gene Mutation