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A Phase 1 Study of PRT3645 in Participants With Select Advanced or Metastatic Solid Tumors

Published: September 30, 2022

Primary Outcome Measures

  1. Dose limiting toxicity (DLT) of PRT3645 [ Time Frame: Baseline through Day 28 ]
    Dose limiting toxicity will be evaluated over the 28-day observation period
  2. Safety and tolerability of PRT3645: AEs, CTCAE Assessments [ Time Frame: Baseline through approximately 2 years ]
    Safety and tolerability will be evaluated by incidence of DLTs, laboratory measurements, severity of adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.
  3. Maximally tolerated dose (MTD)/Recommended phase 2 dose (RP2D) of PRT3645 [ Time Frame: Baseline through approximately 2 years ]
    The MTD/RP2D will be established for further investigation in participants with advanced solid tumors

Secondary Outcome Measures

  1. Efficacy of PRT3645: Tumor assessment and responses [ Time Frame: Baseline through approximately 2 years ]
    Objective response rate (ORR), Progression-free survival (PFS), Disease control rate (DCR) and Duration of response (DOR) will use RECIST v1.1, mRECIST v1.1, and/or RANO as primary measure for tumor assessment and response.
  2. Pharmacokinetic profile of PRT3645: Maximum observed plasma concentration [ Time Frame: Baseline through approximately 2 years ]
    PRT3645 pharmacokinetics will be calculated including the maximum observed plasma concentration.
  3. Pharmacodynamic effect of PRT3645: Target engagement [ Time Frame: Baseline through approximately 2 years ]
    Pharmacodynamic effect of PRT3645 demonstrating target engagement by assessment of phosphorylation of Rb.

Inclusion Criteria

  • Histologically confirmed advanced, recurrent, or metastatic solid tumor malignancy that have either progress or ineligible for standard of care therapy:
    1. HR+ and HER2-negative or HR+ and HER2+breast cancer
    2. Recurrent GBM (IDH wild type) or CDKN2A/B homozygous deleted IDH-mutant astrocytoma
    3. KRAS-mutant NSCLC
    4. CDK pathway alternation in any of the following tumor types: malignant mesothelioma, HPV-negative HNSCC (including oral cavity, oropharynx, hypopharynx, and larynx), sarcoma, or NSCLC
  • Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures
  • Must have measurable or non-measureable (but evaluable) disease
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 and Karnofsky Performance Status (KPS) ≥80%.
  • Adequate organ function.
  • Able to swallow and retain oral medication.
  • Must provide either archival or fresh tumor tissue sample during screening.

Exclusion Criteria

  • Participants with advanced, symptomatic, extensive visceral disease.
  • Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, any upper gastrointestinal surgery including gastric resection, known malabsorption syndrome, or other condition that may impair absorption of PRT3645.
  • Treatment with strong inhibitors of CYP3A4.
  • 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.
  • Clinically significant or uncontrolled cardiac disease, uncontrolled electrolyte disorders, uncontrolled or symptomatic CNS metastases or leptomeningeal disease.
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