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Completed

NCT Number: NCT05639751

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

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.

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Key information

Conditions

Advanced Solid Tumor Metastatic Solid Tumor Neoplasm Metastasis Neoplasms Neoplastic Processes Non-small Cell Lung Cancers Pathologic Processes Pathological Conditions, Signs and Symptoms SMARCA4 Gene Mutation

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

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

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

PRT3789

Drug

PRT3789 will be administered by intravenous infusion

docetaxel

Drug

Docetaxel will be administered by intravenous infusion

Primary outcomes

  1. 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

  2. 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)

  3. 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

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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)

  7. 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

Sponsors and collaborators

Lead sponsor

Prelude Therapeutics

Industry

Registry information

Official study 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

Important dates

Study start
2023
Primary completion
2025
Study completion
2025
First posted
Dec 6, 2022
Registry last updated
Oct 16, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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