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

NCT ID: NCT05639751

Last Updated: 2025-10-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

135 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-05-02

Study Completion Date

2025-10-01

Brief Summary

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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.

Detailed Description

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This is an open-label, multi-center, dose-escalation, first in human, Phase 1 study of PRT3789 as monotherapy and in combination with docetaxel, a SMARCA2 degrader, evaluating participants with advanced or metastatic solid tumors with loss of SMARCA4 due to truncating mutation and/or deletion. The study will evaluate escalating doses of PRT3789 until the MTD or RP2D is determined. Taking into account pharmacokinetic and pharmacodynamic data from the preceding dose levels, the dose may be escalated until a dose limiting toxicity is identified. Approximately 186 participants will be enrolled in monotherapy, dose escalation, backfill, and combination cohorts.

Conditions

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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PRT3789 Monotherapy

PRT3789 will be administered by intravenous infusion

Group Type EXPERIMENTAL

PRT3789

Intervention Type DRUG

PRT3789 will be administered by intravenous infusion

PRT3789/Docetaxel Combination

PRT3789 and Docetaxel will be administered by intravenous infusions

Group Type EXPERIMENTAL

PRT3789

Intervention Type DRUG

PRT3789 will be administered by intravenous infusion

Docetaxel

Intervention Type DRUG

Docetaxel will be administered by intravenous infusion

Interventions

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PRT3789

PRT3789 will be administered by intravenous infusion

Intervention Type DRUG

Docetaxel

Docetaxel will be administered by intravenous infusion

Intervention Type DRUG

Eligibility Criteria

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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 (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)

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 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Prelude Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of California, Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status

UCLA Hematology/Oncology - Santa Monica

Santa Monica, California, United States

Site Status

Smilow Cancer Hospital Phase 1 Unit

New Haven, Connecticut, United States

Site Status

AdventHealth Medical Group Oncology Research at Celebration

Celebration, Florida, United States

Site Status

Mayo Clinic, Jacksonville

Jacksonville, Florida, United States

Site Status

Winship Cancer Institute

Atlanta, Georgia, United States

Site Status

Northwestern Memorial Hospital

Chicago, Illinois, United States

Site Status

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Mayo Clinic, Rochester

Rochester, Minnesota, United States

Site Status

Washington University School of Medicine - Siteman Cancer Center

St Louis, Missouri, United States

Site Status

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, United States

Site Status

New York Presbyterian Hospital - Columbia University Medical Center

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Providence Cancer Institute Franz Clinic

Portland, Oregon, United States

Site Status

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

NEXT Virginia

Fairfax, Virginia, United States

Site Status

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

Bordeaux, , France

Site Status

Centre Leon Berard

Lyon, , France

Site Status

lnstitut Paoli Calmettes

Marseille, , France

Site Status

Oncopole Claudius Regaud IUCT ONCOPOLE

Toulouse, , France

Site Status

Institut Gustave Roussy

Villejuif, , France

Site Status

Leids Universitair Medisch Centrum

Leiden, , Netherlands

Site Status

National University Hospital

Singapore, Singapore, Singapore

Site Status

National Cancer Centre Singapore

Singapore, Singapore, Singapore

Site Status

START Barcelona - HM Nou Delfos

Barcelona, Barcelona, Spain

Site Status

START MADRID - FJD Hospital Universitario Fundacion Jimenez Diaz

Madrid, Madrid, Spain

Site Status

Hospital Universitario HM Sanchinarro

Madrid, Madrid, Spain

Site Status

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Site Status

Countries

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United States France Netherlands Singapore Spain

Other Identifiers

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PRT3789-01

Identifier Type: -

Identifier Source: org_study_id

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