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

NCT06560645 | Terminated Phase 1 FDA Drug

• 1 other identifier: PRT7732-01
• Study Type: interventional
• Target: 42
• Locations: 6 countries
• Sites: 28

Brief Summary

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.

Conditions

Advanced Solid Tumor; Metastatic Solid Tumor; Non-small Cell Lung Carcinoma; SMARCA4 Mutation; Esophageal Adenocarcinoma; Esophageal Squamous Cell Carcinoma; Gastric Adenocarcinoma; Gastric Squamous Cell Carcinoma; Gastroesophageal Junction Adenocarcinoma; Gastroesophageal Junction Squamous Cell Carcinoma

Keywords

Advanced Solid Tumors; BRG1; BRM; Degrader; Metastatic Solid Tumors; Non-Small Cell Lung Cancers; NSCLC; PRT7732; SMARCA2; SMARCA4; Esophageal Adenocarcinoma; Esophageal Squamous Cell Carcinoma; Gastric Adenocarcinoma; Gastric Squamous Cell Carcinoma; Gastroesophageal Junction Adenocarcinoma; Gastroesophageal Junction Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (5)

• Efficacy of PRT7732

  Baseline through study completion, an average of 2 years

• Pharmacokinetic profile of PRT7732 as a single agent: 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

  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)

  Baseline through study completion, an average of 2 years

• Pharmacodynamic effects of PRT7732 as a single agent

  Baseline through study completion, an average of 2 years

Study Arms (1)

PRT7732

EXPERIMENTAL

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

Interventions

PRT7732 DRUG

PRT7732 capsules will be self-administered once daily at the dose-level assigned

PRT7732

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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).

Sponsors & Collaborators

• Prelude Therapeutics: lead

Study Sites (28)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94158, United States

Location

Brigitte Harris Cancer Pavilion

Detroit, Michigan, 48202, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Memorial Sloan Kettering Cancer Center - Main Campus

New York, New York, 10065, United States

Location

UNC Hospitals, The University of North Carolina Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Virginia Comprehensive Cancer Center

Charlottesville, Virginia, 22903, United States

Location

Border Medical Oncology Research Unit

Albury, New South Wales, 2640, Australia

Location

Southern Highlands Cancer Centre

Bowral, New South Wales, 2576, Australia

Location

Scientia Clinical Research Ltd

Randwick, New South Wales, 2031, Australia

Location

Monash Health

Clayton, Victoria, 3168, Australia

Location

Linear Clinical Research Ltd

Nedlands, Western Australia, 6009, Australia

Location

University Clinic Cologne, Clinic for Internal Medicine

Cologne, North Rhine-Westfalia, 50937, Germany

Location

Technische Universitat Dresden, Medizinlsche Fakultat Carl Gustav Carus Nationales Centrum fur Tumorerkrankungen Dresden, Early Clinical Trial Unit (NCT/UCC ECTU)

Dresden, Saxony, 01307, Germany

Location

Kindai University Hospital

Sayama, Osaka, 589-8511, Japan

Location

The Univerity of Osaka Hospital

Suita, Osaka, 565-0871, Japan

Location

National Cancer Center Hospital

Chuo Ku, Tokyo, 104-0045, Japan

Location

Cancer Institute Hospital of JFCR

Koto-ku, Tokyo, 135-8550, Japan

Location

National Cancer Center

Goyang-si, Gyeonggi-do, 10408, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Start Madrid-FJD, Hospital Universitario Fundacion Jimenez Diaz-Servicio de Oncologia

Madrid, 28040, Spain

Location

Hospital Universitario HM Sanchinarro

Madrid, 28050, Spain

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma Of Esophagus; Esophageal Squamous Cell Carcinoma

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2024
• First Posted: August 19, 2024
• Study Start: November 4, 2024
• Primary Completion: January 28, 2026
• Study Completion: January 28, 2026
• Last Updated: February 2, 2026

Record last verified: 2026-01

Locations

US (11); ES (3); KR (3); AU (5); DE (2); JP (4)