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

• ClinicalTrials.gov Identifier: NCT05639751
• Recruitment Status: Recruiting
• First Posted: December 6, 2022
• Last Update Posted: April 29, 2024
• Sponsor: Prelude Therapeutics
• Information provided by (Responsible Party): Prelude Therapeutics

Tracking Information

• First Submitted Date: November 11, 2022
• First Posted Date: December 6, 2022
• Last Update Posted Date: April 29, 2024
• Actual Study Start Date: May 2, 2023
• Estimated Primary Completion Date: March 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 15, 2024)

• Dose limiting toxicity (DLT) of PRT3789 monotherapy and in combination with docetaxel [ Time Frame: Baseline through Day 21 ]
  Dose limiting toxicities will be evaluated over the 21-day observation period
• Safety and tolerability of PRT3789 monotherapy and in combination with docetaxel: AEs, CTCAE Assessments [ Time Frame: Baseline through approximately 3 years ]
  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 monotherapy and in combination with docetaxel [ Time Frame: Baseline through approximately 3 years ]
  The MTD/RP2D will be established for further investigation in participants with advanced solid tumors

Original Primary Outcome Measures (submitted: November 28, 2022)

• Dose limiting toxicity (DLT) of PRT3789 [ Time Frame: Baseline through Day 21 ]
  Dose limiting toxicities will be evaluated over the 21-day observation period
• Safety and tolerability of PRT3789: AEs, CTCAE Assessments [ Time Frame: Baseline through approximately 3 years ]
  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 [ Time Frame: Baseline through approximately 3 years ]
  The MTD/RP2D will be established for further investigation in participants with advanced solid tumors

Current Secondary Outcome Measures (submitted: February 15, 2024)

• Efficacy of PRT3789 monotherapy and in combination with docetaxel: Objective response rate (ORR) [ Time Frame: Baseline through approximately 3 years ]
  Best overall response of either complete response (CR) or partial response (PR), as assessed by the investigator per RECIST v1.1
• Efficacy of PRT3789 monotherapy and in combination with docetaxel: Progression-free survival (PFS) [ Time Frame: Baseline through approximately 3 years ]
  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 monotherapy and in combination with docetaxel: Clinical benefit rate (CBR) [ Time Frame: Baseline through approximately 3 years ]
  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 monotherapy and in combination with docetaxel: Duration of response (DOR) [ Time Frame: Baseline through approximately 3 years ]
  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 monotherapy and in combination with docetaxel: Maximum observed plasma concentration [ Time Frame: Baseline through approximately 3 years ]
  Pharmacokinetics will be calculated including the maximum observed plasma concentration
• Pharmacokinetic profile of PRT3789 monotherapy and in combination with docetaxel: Area under the curve [ Time Frame: Baseline through approximately 3 years ]
  Pharmacokinetics will be calculated including the area under the plasma concentration versus time curve (AUC)
• Pharmacodynamic effect of PRT3789 monotherapy and in combination with docetaxel: Target engagement [ Time Frame: Baseline through approximately 3 years ]
  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

Original Secondary Outcome Measures (submitted: November 28, 2022)

• Efficacy of PRT3789: Objective response rate (ORR) [ Time Frame: Baseline through approximately 3 years ]
  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) [ Time Frame: Baseline through approximately 3 years ]
  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) [ Time Frame: Baseline through approximately 3 years ]
  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) [ Time Frame: Baseline through approximately 3 years ]
  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 [ Time Frame: Baseline through approximately 3 years ]
  PRT3789 pharmacokinetics will be calculated including the maximum observed plasma concentration
• Pharmacokinetic profile of PRT3789: Area under the curve [ Time Frame: Baseline through approximately 3 years ]
  PRT3789 pharmacokinetics will be calculated including the area under the plasma concentration versus time curve (AUC)
• Pharmacodynamic effect of PRT3789: Target engagement [ Time Frame: Baseline through approximately 3 years ]
  Pharmacodynamic effect of PRT3789 demonstrating target engagement by assessment of SMARCA2 protein in peripheral blood mononuclear cells (PBMCs)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: PRT3789 Monotherapy and in Combo w/Docetaxel in Participants w/Advanced or Metastatic Solid Tumors w/SMARCA4 Mutation
• 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
• 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.
• Detailed 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.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

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

Study Arms

• Experimental: PRT3789 Monotherapy
  PRT3789 will be administered by intravenous infusion
  Intervention: Drug: PRT3789
• Experimental: PRT3789/Docetaxel Combination
  PRT3789 and Docetaxel will be administered by intravenous infusions
  Interventions:

  • Drug: PRT3789
  • Drug: Docetaxel

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 15, 2024): 118
• Original Estimated Enrollment (submitted: November 28, 2022): 86
• Estimated Study Completion Date: March 2026
• Estimated Primary Completion Date: March 2026 (Final data collection date for primary outcome measure)

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 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Study Contact (Please Do Not Disclose Personal Information); See Email; clinicaltrials@preludetx.com

• Listed Location Countries: France, Netherlands, Singapore, Spain, United States

Administrative Information

• NCT Number: NCT05639751
• Other Study ID Numbers: PRT3789-01
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Prelude Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Prelude Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Prelude Therapeutics
• Verification Date: April 2024