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

NCT06682806 | Terminated Phase 2 FDA Drug

• 4 other identifiers: PRT3789-02KEYNOTE-G02MK-3475-G022024-516889-11-00
• Study Type: interventional
• Target: 6
• Locations: 2 countries
• Sites: 9

Brief Summary

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (4)

• Safety and tolerability of PRT3789 in combination with pembrolizumab as measured by incidence of DLTs (Part 1)

  Safety and tolerability will be evaluated by incidence of dose-limiting toxicities (DLTs)

  Baseline through completion of study, an average of 2 years

• Safety and tolerability of PRT3789 in combination with pembrolizumab as measured by incidence and severity of AEs according to NCI CTCAE (Part 1)

  Safety and tolerability will be evaluated by incidence and severity of 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

• Efficacy of PRT3789 in combination with pembrolizumab in patients with advanced or metastatic esophageal or NSCLC and deleterious SMARCA4 mutation: Objective Response Rate (Part 2)

  Objective response rate defined as the proportion of patients with a confirmed best overall response of either complete response or partial response, as determined per investigator assessment by RECIST v1.1

  Baseline through study completion, an average of 2 years

• Efficacy of PRT3789 in combination with pembrolizumab in patients with advanced or metastatic esophageal or NSCLC and deleterious SMARCA4 mutation: Duration of Response (Part 2)

  Duration of response defined as the time from the date of the first documented response (complete response or partial response) to the earliest date of disease progression, as determined per investigator assessment by RECIST v1.1, or death due to any cause

  Baseline through study completion, an average of 2 years

Secondary Outcomes (11)

• Efficacy of PRT3789 in combination with pembrolizumab: Objective Response Rate (Part 1)

  Baseline through study completion, an average of 2 years

• Efficacy of PRT3789 in combination with pembrolizumab: Duration of Response (Part 1)

  Baseline through study completion, an average of 2 years

• Efficacy of PRT3789 in combination with pembrolizumab (part 1 and part 2): Clinical Benefit Response

  Baseline through study completion, an average of 2 years

• Efficacy of PRT3789 in combination with pembrolizumab (part 1 and part 2): Progression-Free Survival

  Baseline through study completion, an average of 2 years

• Efficacy of PRT3789 in combination with pembrolizumab (part 1 and part 2): Overall Survival

  Baseline through study completion, an average of 2 years

Study Arms (1)

PRT3789/Pembrolizumab combination

EXPERIMENTAL

PRT3789 is administered as an intravenous infusion once weekly for 3 weeks; Pembrolizumab is administered at 200 mg as an intravenous infusion over 30 min every 3 weeks

Drug: PRT3789; Drug: pembrolizumab

Interventions

PRT3789 DRUG

PRT3789 is administered as an intravenous infusion once weekly for 3 weeks

PRT3789/Pembrolizumab combination

pembrolizumab DRUG

Pembrolizumab is administered at 200 mg as an intravenous infusion over 30 min every 3 weeks

Also known as: KEYTRUDA®

PRT3789/Pembrolizumab combination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Prelude Therapeutics: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (9)

Florida Cancer Specialists

West Palm Beach, Florida, 33401, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

Location

Tennessee Oncology, PLLC - Greco-Hainsworth Centers for Research

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

IOB - Next Oncology - Hospital Quironsalud Barcelona

Barcelona, 08023, Spain

Location

START Barcelona - HM Nou Delfos

Barcelona, 08023, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz - Servicio de Oncologia

Madrid, 28040, Spain

Location

MeSH Terms

Conditions

Esophageal Neoplasms; Neoplasm Metastasis

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2024
• First Posted: November 12, 2024
• Study Start: June 3, 2025
• Primary Completion: January 23, 2026
• Study Completion: January 23, 2026
• Last Updated: February 2, 2026

Record last verified: 2026-01

Locations

US (6); ES (3)