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

Advanced Solid Tumor Clinical Trial

Official title:

A Phase 1 Open-Label, Multi-Center, Safety and Efficacy Study of PRT3789 as Monotherapy and in Combination With Docetaxel in Participants With Advanced or Metastatic Solid Tumors With a SMARCA4 Mutation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05639751
• Other study ID #: PRT3789-01
• Status: Recruiting
• Phase: Phase 1
• Start date: May 2, 2023
• Est. completion date: March 2026

Study information

• Verified date: April 2024
• Source: Prelude Therapeutics
• Contact: Study Contact (Please Do Not Disclose Personal Information)
• Phone: See Email
• Email: clinicaltrials[@]preludetx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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 118 participants will be enrolled in monotherapy, dose escalation, backfill, and combination cohorts.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 118
• Est. completion date: March 2026
• Est. primary completion date: March 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Carcinoma, Non-Small-Cell Lung
• Metastatic Solid Tumor
• Neoplasms
• Non-small Cell Lung Cancers
• SMARCA4 Gene Mutation

Intervention

Drug:
• PRT3789
PRT3789 will be administered by intravenous infusion
• Docetaxel
Docetaxel will be administered by intravenous infusion

Locations

Country	Name	City	State
France	lnstitut Bergonie Centre Regionale de Lutte Contre le cancer, Service Oncologie-Medicale	Bordeaux
France	Centre Leon Berard	Lyon Cedex 08
France	Institut Gustave Roussy	Villejuif Cedex
Netherlands	Leids Universitair Medisch Centrum	Leiden
Singapore	National Cancer Centre Singapore	Singapore
Singapore	National University Hospital	Singapore
Spain	START Barcelona - HM Nou Delfos	Barcelona
Spain	Hospital Universitario HM Sanchinarro	Madrid
Spain	START MADRID - FJD Hospital Universitario Fundacion Jimenez Diaz	Madrid
United States	Winship Cancer Institute	Atlanta	Georgia
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	AdventHealth Medical Group Oncology Research at Celebration	Celebration	Florida
United States	Cleveland Clinic	Cleveland	Ohio
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	NEXT Virginia	Fairfax	Virginia
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Smilow Cancer Hospital Phase 1 Unit	New Haven	Connecticut
United States	Laura & Isaac Perlmutter Cancer Center at NYU Langone Health	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	New York Presbyterian Hospital - Columbia University Medical Center	New York	New York
United States	University of California, Davis Comprehensive Cancer Center	Sacramento	California
United States	Washington University School of Medicine - Siteman Cancer Center	Saint Louis	Missouri
United States	UCLA Hematology/Oncology - Santa Monica	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
Prelude Therapeutics

Countries where clinical trial is conducted

United States,  France,  Netherlands,  Singapore,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	Efficacy of PRT3789 monotherapy and in combination with docetaxel: 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	Baseline through approximately 3 years
Secondary	Efficacy of PRT3789 monotherapy and in combination with docetaxel: 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	Baseline through approximately 3 years
Secondary	Efficacy of PRT3789 monotherapy and in combination with docetaxel: 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	Baseline through approximately 3 years
Secondary	Efficacy of PRT3789 monotherapy and in combination with docetaxel: 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	Baseline through approximately 3 years
Secondary	Pharmacokinetic profile of PRT3789 monotherapy and in combination with docetaxel: Maximum observed plasma concentration	Pharmacokinetics will be calculated including the maximum observed plasma concentration	Baseline through approximately 3 years
Secondary	Pharmacokinetic profile of PRT3789 monotherapy and in combination with docetaxel: Area under the curve	Pharmacokinetics will be calculated including the area under the plasma concentration versus time curve (AUC)	Baseline through approximately 3 years
Secondary	Pharmacodynamic effect of PRT3789 monotherapy and in combination with docetaxel: Target engagement	Pharmacodynamic effect of PRT3789 monotherapy and in combination with docetaxel demonstrating target engagement by assessment of SMARCA2 protein in peripheral blood mononuclear cells (PBMCs) and tumor tissue	Baseline through approximately 3 years