A Phase I 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

Study Identifier:
PRT3789-01
CT.gov Identifier:
NCT05639751
EudraCT Identifier:
202250000000
EU Trial (CTIS) Number:
2022-502850-14-00
Study Contact Information:
(210) 593-5651 or [email protected]
Study Complete

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Study Summary

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.

A Bayesian optimal interval method will inform dose escalation, de-escalation, or maintenance based on the number of patients with dose-limiting toxicities (DLTs), until the maximum tolerated dose and recommended phase 2 dose (RP2D) are determined.

To assess clinical activity in a more homogeneous group of patients with high unmet need, at the biologically active dose, to support planned discussions with regulatory agencies

To hypothesize that selective SMARCA2 degradation through synthetic lethality with PRT3789 will be an effective therapy for SMARCA4 mutated cancer.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Solid Tumor
  • Non-Small Cell Lung Cancer
  • Gene Mutations
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Experimental: PRT3789
    • Read More
  • Drug: Experimental: PRT3789/Docetaxel Combination
  • Drug: Drug: Docetaxel
  • Drug: Biomarker selected by local NGS or IHC in tumor tissue or blood
  • Drug: Successive cohorts will receive escalating doses of intravenous PRT3789 once weekly for 3 weeks (1 cycle). PRT3789 treatment will continue until disease progression or unacceptable toxicity, whichever occurs first.
  • Drug: PRT3789 is given intravenously weekly.
  • Drug: EORTC-NCI-AACR 2024:
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Study Complete

    Requirements information
    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

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Barcelona
    Barcelona, Spain, 08023
    Investigator
    Tatiana Hernandez Guerrero
    Status
    Recruiting
    Condition(s) Treated at Site
    Solid Tumor
    Non-Small Cell Lung Cancer
    Gene Mutations