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

NCT05639751
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Phase
Phase 1
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Recruitment status
Completed
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Participants
135
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Lead sponsor
Prelude Therapeutics
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Start date
2023-05-02
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Number of sites
32
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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.
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Short title
PRT3789 Monotherapy and in Combo w/Docetaxel in Participants w/Advanced or Metastatic Solid Tumors w/SMARCA4 Mutation
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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
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Completed
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Phase
Phase 1
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Study type
Interventional
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Completion date
2025-10-01
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First posted
2022-12-06
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Registry last updated
2025-10-16
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Primary completion date
2025-10-01
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Start date
2023-05-02
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Actual participants
135
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Participants
135
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Participant count basis
Actual
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Protocol amendments
5
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Number of sites
32
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
Prelude Therapeutics
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05639751
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ClinicalTrials.gov ID
NCT05639751
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Registry record
Open registry record
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Allocation
Not randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
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  1. Dose limiting toxicity (DLT) of PRT3789 monotherapy and in combination with docetaxel

    Timeframe: 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

    Timeframe: 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

    Timeframe: Baseline through approximately 3 years

    The MTD/RP2D will be established for further investigation in participants with advanced solid tumors

  1. Efficacy of PRT3789 monotherapy and in combination with docetaxel: Objective response rate (ORR)

    Timeframe: 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)

    Timeframe: 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)

    Timeframe: 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)

    Timeframe: 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

    Timeframe: 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

    Timeframe: 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

    Timeframe: 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

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • 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)

  • 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
Sources for eligibility
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  • University of California, Davis Comprehensive Cancer CenterSacramento, United States
  • UCLA Hematology/Oncology - Santa MonicaSanta Monica, United States
  • Smilow Cancer Hospital Phase 1 UnitNew Haven, United States
  • AdventHealth Medical Group Oncology Research at CelebrationCelebration, United States
  • Mayo Clinic, JacksonvilleJacksonville, United States
  • Winship Cancer InstituteAtlanta, United States
  • Northwestern Memorial HospitalChicago, United States
  • Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, United States
  • Massachusetts General HospitalBoston, United States
  • Dana Farber Cancer InstituteBoston, United States
  • Mayo Clinic, RochesterRochester, United States
  • Washington University School of Medicine - Siteman Cancer CenterSt Louis, United States
  • Laura & Isaac Perlmutter Cancer Center at NYU Langone HealthNew York, United States
  • New York Presbyterian Hospital - Columbia University Medical CenterNew York, United States
  • Memorial Sloan Kettering Cancer CenterNew York, United States
  • University Hospitals Cleveland Medical CenterCleveland, United States
  • Cleveland ClinicCleveland, United States
  • Providence Cancer Institute Franz ClinicPortland, United States
  • The University of Texas MD Anderson Cancer CenterHouston, United States
  • NEXT VirginiaFairfax, United States
  • lnstitut Bergonie Centre Regionale de Lutte Contre le cancer, Service Oncologie-MedicaleBordeaux, France
  • Centre Leon BerardLyon, France
  • lnstitut Paoli CalmettesMarseille, France
  • Oncopole Claudius Regaud IUCT ONCOPOLEToulouse, France
  • Institut Gustave RoussyVillejuif, France

And 7 more, listed on the interactive page.

Sources for sites
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Related records

Drugs (1)

Lead sponsors (1)

Conditions (1)

Targets (16)