TERMINATED

A Study of PRT3789 in Combination With Pembrolizumab in Patients With Advanced or Metastatic Solid Tumors With a SMARCA4 Mutation

Conditions

Advanced Solid Tumor Esophageal Cancer Metastatic Solid Tumor Non-small Cell Lung Cancers SMARCA4 Gene Mutation Advanced Solid Tumors BRG1 BRM Metastatic Solid Tumors NSCLC PRT3789 Pembrolizumab Keytruda®SMARCA2 Degrader SMARCA4

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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 2 an open-label, multi-center study to determine the safety, tolerability, efficacy, pharmacokinetics, pharmacodynamics, and anti-tumor activity of PRT3789 in combination with pembrolizumab in patients with advanced, recurrent or metastatic solid tumors with a SMARCA4 mutation.

Official Title

A Phase 2, Safety and Efficacy Study of PRT3789 in Combination With Pembrolizumab in Patients With Advanced or Metastatic Solid Tumors With a SMARCA4 Mutation

Quick Facts

Study Start:2025-06-03

Study Completion:2026-01-23

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:TERMINATED

Study ID

NCT06682806

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
* Patients who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations and other study procedures, including providing informed consent. * Patients must either progress on standard of care therapy or be ineligible for standard of care therapy in order to be eligible for enrollment on the study. * Part 1 Safety Run-in: Patients with advanced, recurrent, or metastatic histologically or cytologically confirmed solid tumor malignancy and any mutation of SMARCA4 detected by next generation sequencing in tumor tissue or blood, or absence of SMARCA4 protein (BRG1). Part 2 Main Study: Patients with advanced, recurrent, or metastatic histologically confirmed esophageal cancer or NSCLC and have a deleterious SMARCA4 mutation, or absence of SMARCA4 protein (BRG1) detected by immunohistochemistry in tumor tissue using a clinically validated laboratory test. * Part 1 Run-in: Measurable or non-measurable (but evaluable) disease per RECIST v1.1 as assessed by the local site investigator/radiologist. Part 2 Main Study: Measurable disease per RECIST v1.1 as assessed by the local site investigator/radiologist. Lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions. * Willingness and ability to provide tumor tissue (i.e., archived or fresh tumor biopsy if archived tumor tissue is unavailable) * Adequately controlled blood pressure with or without antihypertensive medications. * Patients with HIV must have well-controlled HIV on antiretroviral therapy. * Adequate organ function	* Patients who have adverse events due to previous anticancer therapies and/or complications from prior surgical intervention must have recovered to ≤ Grade 1 or baseline before starting study treatment. Patients with endocrine-related AEs who are adequately treated with hormone replacement or patients who have ≤ Grade 2 neuropathy are eligible. * Other acute or chronic medical or psychiatric conditions that would make the patient inappropriate for entry into this study. * Patients with solid tumors with a known concomitant SMARCA2 mutation or loss of protein expression. * Uncontrolled or symptomatic central nervous system (CNS) metastases or leptomeningeal disease and/or carcinomatous meningitis). * History of or current (noninfectious) pneumonitis/interstitial lung disease * Diagnosis of immunodeficiency disease/disorder. * Known additional malignancy that is progressing or has required active treatment within the past 3 years. * Patients who received prior treatment with an agent directed to a stimulatory or co-inhibitory T-cell receptor. * Currently taking a strong or moderate CYP3A4 inhibitor or inducer and St. John's Wort and are unable to discontinue use within 15 days of the first dose of study treatment. * Receipt of any targeted therapy directed against BRM/BRG1 (SMARCA2/SMARCA4). * Pregnant or breastfeeding or plan to become pregnant during the duration of the study.

Inclusion Criteria

Exclusion Criteria

* Patients who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations and other study procedures, including providing informed consent.
* Patients must either progress on standard of care therapy or be ineligible for standard of care therapy in order to be eligible for enrollment on the study.
* Part 1 Safety Run-in: Patients with advanced, recurrent, or metastatic histologically or cytologically confirmed solid tumor malignancy and any mutation of SMARCA4 detected by next generation sequencing in tumor tissue or blood, or absence of SMARCA4 protein (BRG1). Part 2 Main Study: Patients with advanced, recurrent, or metastatic histologically confirmed esophageal cancer or NSCLC and have a deleterious SMARCA4 mutation, or absence of SMARCA4 protein (BRG1) detected by immunohistochemistry in tumor tissue using a clinically validated laboratory test.
* Part 1 Run-in: Measurable or non-measurable (but evaluable) disease per RECIST v1.1 as assessed by the local site investigator/radiologist. Part 2 Main Study: Measurable disease per RECIST v1.1 as assessed by the local site investigator/radiologist. Lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions.
* Willingness and ability to provide tumor tissue (i.e., archived or fresh tumor biopsy if archived tumor tissue is unavailable)
* Adequately controlled blood pressure with or without antihypertensive medications.
* Patients with HIV must have well-controlled HIV on antiretroviral therapy.
* Adequate organ function

* Patients who have adverse events due to previous anticancer therapies and/or complications from prior surgical intervention must have recovered to ≤ Grade 1 or baseline before starting study treatment. Patients with endocrine-related AEs who are adequately treated with hormone replacement or patients who have ≤ Grade 2 neuropathy are eligible.
* Other acute or chronic medical or psychiatric conditions that would make the patient inappropriate for entry into this study.
* Patients with solid tumors with a known concomitant SMARCA2 mutation or loss of protein expression.
* Uncontrolled or symptomatic central nervous system (CNS) metastases or leptomeningeal disease and/or carcinomatous meningitis).
* History of or current (noninfectious) pneumonitis/interstitial lung disease
* Diagnosis of immunodeficiency disease/disorder.
* Known additional malignancy that is progressing or has required active treatment within the past 3 years.
* Patients who received prior treatment with an agent directed to a stimulatory or co-inhibitory T-cell receptor.
* Currently taking a strong or moderate CYP3A4 inhibitor or inducer and St. John's Wort and are unable to discontinue use within 15 days of the first dose of study treatment.
* Receipt of any targeted therapy directed against BRM/BRG1 (SMARCA2/SMARCA4).
* Pregnant or breastfeeding or plan to become pregnant during the duration of the study.

Contacts and Locations

Study Locations (Sites)

Florida Cancer Specialists

West Palm Beach, Florida, 33401

United States

Karmanos Cancer Institute

Detroit, Michigan, 48201

United States

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601

United States

SCRI Oncology Partners

Nashville, Tennessee, 37203

United States

Tennessee Oncology, PLLC - Greco-Hainsworth Centers for Research

Nashville, Tennessee, 37203

United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030

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 Date2025-06-03

Study Completion Date2026-01-23

Study Record Updates

Study Start Date2025-06-03

Study Completion Date2026-01-23

Terms related to this study

Keywords Provided by Researchers

Advanced Solid Tumors
BRG1
BRM
Esophageal Cancer
Metastatic Solid Tumors
Non-Small Cell Lung Cancers
NSCLC
PRT3789
Pembrolizumab
Keytruda®
SMARCA2 Degrader
SMARCA4

Additional Relevant MeSH Terms

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