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

NCT05639751 | Completed Phase 1 FDA Drug

• 1 other identifier: PRT3789-01
• Study Type: interventional
• Target: 135
• Locations: 5 countries
• Sites: 32

Brief Summary

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (3)

• Dose limiting toxicity (DLT) of PRT3789 monotherapy and in combination with docetaxel

  Dose limiting toxicities will be evaluated over the 21-day observation period

  Baseline through Day 21

• Safety and tolerability of PRT3789 monotherapy and in combination with docetaxel: AEs, CTCAE Assessments

  Safety and tolerability will be evaluated by incidence of DLTs, laboratory measurements, 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 approximately 3 years

• Maximum tolerated dose (MTD)/ Recommended phase 2 dose (RP2D) of PRT3789 monotherapy and in combination with docetaxel

  The MTD/RP2D will be established for further investigation in participants with advanced solid tumors

  Baseline through approximately 3 years

Secondary Outcomes (7)

• Efficacy of PRT3789 monotherapy and in combination with docetaxel: Objective response rate (ORR)

  Baseline through approximately 3 years

• Efficacy of PRT3789 monotherapy and in combination with docetaxel: Progression-free survival (PFS)

  Baseline through approximately 3 years

• Efficacy of PRT3789 monotherapy and in combination with docetaxel: Clinical benefit rate (CBR)

  Baseline through approximately 3 years

• Efficacy of PRT3789 monotherapy and in combination with docetaxel: Duration of response (DOR)

  Baseline through approximately 3 years

• Pharmacokinetic profile of PRT3789 monotherapy and in combination with docetaxel: Maximum observed plasma concentration

  Baseline through approximately 3 years

Study Arms (2)

PRT3789 Monotherapy

EXPERIMENTAL

PRT3789 will be administered by intravenous infusion

Drug: PRT3789

PRT3789/Docetaxel Combination

EXPERIMENTAL

PRT3789 and Docetaxel will be administered by intravenous infusions

Drug: PRT3789; Drug: Docetaxel

Interventions

PRT3789 DRUG

PRT3789 will be administered by intravenous infusion

PRT3789 Monotherapy; PRT3789/Docetaxel Combination

Docetaxel DRUG

Docetaxel will be administered by intravenous infusion

PRT3789/Docetaxel Combination

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 (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)

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 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

Sponsors & Collaborators

• Prelude Therapeutics: lead

Study Sites (32)

University of California, Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

UCLA Hematology/Oncology - Santa Monica

Santa Monica, California, 90404, United States

Location

Smilow Cancer Hospital Phase 1 Unit

New Haven, Connecticut, 06511, United States

Location

AdventHealth Medical Group Oncology Research at Celebration

Celebration, Florida, 34747, United States

Location

Mayo Clinic, Jacksonville

Jacksonville, Florida, 32224, United States

Location

Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic, Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine - Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, 10016, United States

Location

New York Presbyterian Hospital - Columbia University Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Providence Cancer Institute Franz Clinic

Portland, Oregon, 97213, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

NEXT Virginia

Fairfax, Virginia, 22031, United States

Location

lnstitut Bergonie Centre Regionale de Lutte Contre le cancer, Service Oncologie-Medicale

Bordeaux, 33000, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

lnstitut Paoli Calmettes

Marseille, 13009, France

Location

Oncopole Claudius Regaud IUCT ONCOPOLE

Toulouse, 31059, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Leids Universitair Medisch Centrum

Leiden, 2333 ZA, Netherlands

Location

National University Hospital

Singapore, Singapore, 119074, Singapore

Location

National Cancer Centre Singapore

Singapore, Singapore, 168583, Singapore

Location

START Barcelona - HM Nou Delfos

Barcelona, Barcelona, 08023, Spain

Location

START MADRID - FJD Hospital Universitario Fundacion Jimenez Diaz

Madrid, Madrid, 28040, Spain

Location

Hospital Universitario HM Sanchinarro

Madrid, Madrid, 28050, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Docetaxel

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Design

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

Study Record Dates

• First Submitted: November 11, 2022
• First Posted: December 6, 2022
• Study Start: May 2, 2023
• Primary Completion: October 1, 2025
• Study Completion: October 1, 2025
• Last Updated: October 16, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5); NL (1); ES (4); SG (2); US (20)