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A Study of PRT3789 in Participants With Select Advanced or Metastatic Solid Tumors With a SMARCA4 Mutation

Primary Purpose

Advanced Solid Tumor, Metastatic Solid Tumor, Non-small Cell Lung Cancers

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
PRT3789
Sponsored by
Prelude Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Solid Tumor focused on measuring Advanced Solid Tumors, BRG1, BRM, Metastatic Solid Tumors, Non-Small Cell Lung Cancers, NSCLC, PRT3789, SMARCA2 Degrader, SMARCA4

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 loss of SMARCA4 due to truncating mutation and/or deletion by local testing that have either progress on or ineligible for standard of care therapy Must have measurable or non-measureable (but evaluable) disease 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

Sites / Locations

  • University of California, Davis Comprehensive Cancer Center
  • UCLA Hematology/Oncology - Santa MonicaRecruiting
  • AdventHealth Medical Group Oncology Research at CelebrationRecruiting
  • Massachusetts General HospitalRecruiting
  • Dana Farber Cancer InstituteRecruiting
  • Laura & Isaac Perlmutter Cancer Center at NYU Langone HealthRecruiting
  • Memorial Sloan Kettering Cancer CenterRecruiting
  • University Hospitals Cleveland Medical CenterRecruiting
  • Cleveland ClinicRecruiting
  • The University of Texas MD Anderson Cancer CenterRecruiting
  • NEXT VirginiaRecruiting
  • START MADRID - FJD Hospital Universitario Fundacion Jimenez DiazRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PRT3789

Arm Description

PRT3789 will be administered by intravenous infusion

Outcomes

Primary Outcome Measures

Dose limiting toxicity (DLT) of PRT3789
Dose limiting toxicities will be evaluated over the 21-day observation period
Safety and tolerability of PRT3789: 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)
Maximum tolerated dose (MTD)/ Recommended phase 2 dose (RP2D) of PRT3789
The MTD/RP2D will be established for further investigation in participants with advanced solid tumors

Secondary Outcome Measures

Efficacy of PRT3789: Objective response rate (ORR)
Best overall response of either complete response (CR) or partial response (PR), as assessed by the investigator per RECIST v1.1
Efficacy of PRT3789: Progression-free survival (PFS)
Duration from Day 1 to the earliest date of first disease progression, as assessed by the investigator per RECIST v1.1, discontinuation because of disease progression, or death due to any cause
Efficacy of PRT3789: Clinical benefit rate (CBR)
Best overall response of CR, PR, or durable stable disease (24 weeks or longer duration), as assessed by the investigator per RECIST v1.1
Efficacy of PRT3789: Duration of response (DOR)
Duration from time of first observed response (CR or PR) to the earliest date of disease progression, as assessed by the investigator per RECIST v1.1, or death due to any cause
Pharmacokinetic profile of PRT3789: Maximum observed plasma concentration
PRT3789 pharmacokinetics will be calculated including the maximum observed plasma concentration
Pharmacokinetic profile of PRT3789: Area under the curve
PRT3789 pharmacokinetics will be calculated including the area under the plasma concentration versus time curve (AUC)
Pharmacodynamic effect of PRT3789: Target engagement
Pharmacodynamic effect of PRT3789 demonstrating target engagement by assessment of SMARCA2 protein in peripheral blood mononuclear cells (PBMCs)

Full Information

First Posted
November 11, 2022
Last Updated
October 3, 2023
Sponsor
Prelude Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT05639751
Brief Title
A Study of PRT3789 in Participants With Select Advanced or Metastatic Solid Tumors With a SMARCA4 Mutation
Official Title
A Phase 1 Open-Label, Multi-Center, Safety and Efficacy Study of PRT3789 in Participants With Select Advanced or Metastatic Solid Tumors With a SMARCA4 Mutation
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 2, 2023 (Actual)
Primary Completion Date
March 2026 (Anticipated)
Study Completion Date
March 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Prelude Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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, 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
This is an open-label, multi-center, dose-escalation, first in human, Phase 1 study of PRT3789, a SMARCA2 degrader, evaluating participants with selected 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 86 participants will be enrolled in dose escalation and backfill cohorts.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
86 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
PRT3789
Arm Type
Experimental
Arm Description
PRT3789 will be administered by intravenous infusion
Intervention Type
Drug
Intervention Name(s)
PRT3789
Intervention Description
PRT3789 will be administered by intravenous infusion
Primary Outcome Measure Information:
Title
Dose limiting toxicity (DLT) of PRT3789
Description
Dose limiting toxicities will be evaluated over the 21-day observation period
Time Frame
Baseline through Day 21
Title
Safety and tolerability of PRT3789: AEs, CTCAE Assessments
Description
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)
Time Frame
Baseline through approximately 3 years
Title
Maximum tolerated dose (MTD)/ Recommended phase 2 dose (RP2D) of PRT3789
Description
The MTD/RP2D will be established for further investigation in participants with advanced solid tumors
Time Frame
Baseline through approximately 3 years
Secondary Outcome Measure Information:
Title
Efficacy of PRT3789: Objective response rate (ORR)
Description
Best overall response of either complete response (CR) or partial response (PR), as assessed by the investigator per RECIST v1.1
Time Frame
Baseline through approximately 3 years
Title
Efficacy of PRT3789: Progression-free survival (PFS)
Description
Duration from Day 1 to the earliest date of first disease progression, as assessed by the investigator per RECIST v1.1, discontinuation because of disease progression, or death due to any cause
Time Frame
Baseline through approximately 3 years
Title
Efficacy of PRT3789: Clinical benefit rate (CBR)
Description
Best overall response of CR, PR, or durable stable disease (24 weeks or longer duration), as assessed by the investigator per RECIST v1.1
Time Frame
Baseline through approximately 3 years
Title
Efficacy of PRT3789: Duration of response (DOR)
Description
Duration from time of first observed response (CR or PR) to the earliest date of disease progression, as assessed by the investigator per RECIST v1.1, or death due to any cause
Time Frame
Baseline through approximately 3 years
Title
Pharmacokinetic profile of PRT3789: Maximum observed plasma concentration
Description
PRT3789 pharmacokinetics will be calculated including the maximum observed plasma concentration
Time Frame
Baseline through approximately 3 years
Title
Pharmacokinetic profile of PRT3789: Area under the curve
Description
PRT3789 pharmacokinetics will be calculated including the area under the plasma concentration versus time curve (AUC)
Time Frame
Baseline through approximately 3 years
Title
Pharmacodynamic effect of PRT3789: Target engagement
Description
Pharmacodynamic effect of PRT3789 demonstrating target engagement by assessment of SMARCA2 protein in peripheral blood mononuclear cells (PBMCs)
Time Frame
Baseline through approximately 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 loss of SMARCA4 due to truncating mutation and/or deletion by local testing that have either progress on or ineligible for standard of care therapy Must have measurable or non-measureable (but evaluable) disease 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Study Contact (Please Do Not Disclose Personal Information)
Phone
See Email
Email
PRT3789-01IV@preludetx.com
Facility Information:
Facility Name
University of California, Davis Comprehensive Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
UCLA Hematology/Oncology - Santa Monica
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Individual Site Status
Recruiting
Facility Name
AdventHealth Medical Group Oncology Research at Celebration
City
Celebration
State/Province
Florida
ZIP/Postal Code
34747
Country
United States
Individual Site Status
Recruiting
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Name
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Name
University Hospitals Cleveland Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Individual Site Status
Recruiting
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Individual Site Status
Recruiting
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Name
NEXT Virginia
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Individual Site Status
Recruiting
Facility Name
START MADRID - FJD Hospital Universitario Fundacion Jimenez Diaz
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Individual Site Status
Recruiting

12. IPD Sharing Statement

Learn more about this trial

A Study of PRT3789 in Participants With Select Advanced or Metastatic Solid Tumors With a SMARCA4 Mutation

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