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

A Phase 1 Open-Label, Multi-Center, Safety and Efficacy Study of PRT7732, an Oral SMARCA2 Degrader, in Patients With Advanced or Metastatic Solid Tumors With a SMARCA4

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.

Study Overview

• Status: Terminated
• Conditions: Gastric Adenocarcinoma; Non-small Cell Lung Carcinoma; Advanced Solid Tumor; Metastatic Solid Tumor; Esophageal Adenocarcinoma; Esophageal Squamous Cell Carcinoma; Gastric Squamous Cell Carcinoma; Gastroesophageal Junction Adenocarcinoma; Gastroesophageal Junction Squamous Cell Carcinoma; SMARCA4 Mutation
• Intervention / Treatment: Drug: PRT7732

Detailed Description

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
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Albury, New South Wales, Australia, 2640
      • Border Medical Oncology Research Unit
    • Bowral, New South Wales, Australia, 2576
      • Southern Highlands Cancer Centre
    • Randwick, New South Wales, Australia, 2031
      • Scientia Clinical Research Ltd
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Linear Clinical Research Ltd
• Germany
  • North Rhine-Westfalia
    • Cologne, North Rhine-Westfalia, Germany, 50937
      • University Clinic Cologne, Clinic for Internal Medicine
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Technische Universitat Dresden, Medizinlsche Fakultat Carl Gustav Carus Nationales Centrum fur Tumorerkrankungen Dresden, Early Clinical Trial Unit (NCT/UCC ECTU)
• Japan
  • Osaka
    • Sayama, Osaka, Japan, 589-8511
      • Kindai University Hospital
    • Suita, Osaka, Japan, 565-0871
      • The Univerity of Osaka Hospital
  • Tokyo
    • Chuo Ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital
    • Koto-ku, Tokyo, Japan, 135-8550
      • Cancer Institute Hospital of JFCR
• South Korea
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University Health System
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, South Korea, 10408
      • National Cancer Center
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro
  • Madrid, Spain, 28040
    • Start Madrid-FJD, Hospital Universitario Fundacion Jimenez Diaz-Servicio de Oncologia
• United States
  • California
    • San Francisco, California, United States, 94158
      • UCSF Helen Diller Family Comprehensive Cancer Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Brigitte Harris Cancer Pavilion
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center - Main Campus
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • UNC Hospitals, The University of North Carolina Chapel Hill
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • SCRI Oncology Partners
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PRT7732; PRT7732 is administered as an oral capsule once daily. Dose escalation/de-escalation decisions will be guided by the BLRM method until the RDE is determined.	Drug: PRT7732; PRT7732 capsules will be self-administered once daily at the dose-level assigned

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limiting toxicity (DLT) of PRT7732	Incidence of dose limiting toxicities for patients in the dose escalation phase	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	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	Baseline through study completion, an average of 2 years
Safety and tolerability as measured by rates of dose modification due to AEs according to NCI CTCAE	Safety and tolerability will be evaluated by dose interruption, modification, and discontinuation due to 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
Maximum tolerated dose (MTD) of PRT7732	Maximum tolerated dose will be determined by the sponsor based on the Safety Review Committee's recommendation considering the totality of the available clinical safety, clinical efficacy, pharmacokinetics (PK), and pharmacodynamic data	Baseline through study completion, an average of 2 years
Recommended dose for expansion (RDE) of PRT7732	The RDE will be determined by the sponsor based on the Safety Review Committee's recommendation considering the totality of the available clinical safety, clinical efficacy, pharmacokinetics (PK), and pharmacodynamic data	Baseline through study completion, an average of 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of PRT7732	Best overall response of either complete response (CR) or partial response (PR), as assessed by the investigator per RECIST v1.1	Baseline through study completion, an average of 2 years
Pharmacokinetic profile of PRT7732 as a single agent: Maximum observed plasma concentration	Pharmacokinetics will be calculated including the maximum observed plasma concentration	Baseline through study completion, an average of 2 years
Pharmacokinetic profile of PRT7732 as a single agent: Area under the curve	Pharmacokinetics will be calculated including the area under the plasma concentration versus time curve (AUC)	Baseline through study completion, an average of 2 years
Pharmacokinetic profile of PRT7732 as a single agent: Time of maximum concentration (Tmax) and half-life (T1/2)	Pharmacokinetic parameters will be calculated using standard non-compartmental techniques	Baseline through study completion, an average of 2 years
Pharmacodynamic effects of PRT7732 as a single agent	The pharmacodynamic effect of PRT7732 demonstrating target engagement by assessment of SMARCA2 protein in peripheral blood mononuclear cells and tumor tissue as assessed by reduction in protein levels of SMARCA2 in peripheral blood mononuclear cells and/or tumor tissue	Baseline through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: Prelude Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2024
• Primary Completion (Actual): January 28, 2026
• Study Completion (Actual): January 28, 2026

Study Registration Dates

• First Submitted: August 6, 2024
• First Submitted That Met QC Criteria: August 16, 2024
• First Posted (Actual): August 19, 2024

Study Record Updates

• Last Update Posted (Actual): February 2, 2026
• Last Update Submitted That Met QC Criteria: January 29, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC; Advanced Solid Tumors; BRG1; BRM; Metastatic Solid Tumors; Non-Small Cell Lung Cancers; SMARCA4; Esophageal Squamous Cell Carcinoma; Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma; Esophageal Adenocarcinoma; Degrader; PRT7732; SMARCA2; Gastric Squamous Cell Carcinoma; Gastroesophageal Junction Squamous Cell Carcinoma
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Lung Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplastic Processes; Esophageal Diseases; Lung Neoplasms; Carcinoma; Neoplasms, Squamous Cell; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Squamous Cell; Esophageal Neoplasms; Pathological Conditions, Signs and Symptoms; Esophageal Squamous Cell Carcinoma; Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma Of Esophagus
• Other Study ID Numbers: PRT7732-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No