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

Sponsor
Prelude Therapeutics (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT05538572
Collaborator
(none)
51
1
24

Study Details

Study Description

Brief Summary

This is a Phase 1 dose-escalation study of PRT3645, a Cyclin-dependent Kinase 4/6 (CDK4/6) inhibitor, in patients with advanced or metastatic solid tumors. The purpose of this study is to investigate the safety, tolerability, dose limiting toxicity, and to determine maximally tolerated dose and recommended phase 2 dose to be used in subsequent development of PRT3645.

Detailed Description

This is an open-label, multicenter, dose-escalation Phase 1 study of PRT3645, a CDK4/6 inhibitor, evaluating patients with selected advanced or metastatic solid tumors including breast cancer (BC), glioblastoma (GBM), non-small cell lung cancer (NSCLC), sarcomas, head and neck squamous cell carcinoma (HNSCC), and malignant mesothelioma. The study plan expects to evaluate approximately eight dose levels however additional dose levels may be explored. Taking into account pharmacokinetic and pharmacodynamic data from the preceding dose levels, the dose may be escalated until a dose limiting toxicity is identified. Up to 15 patients may be enrolled at a dose shown to be tolerated for confirmation of the MTD and/or RP2D.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
51 participants
Allocation:
N/A
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1 Open-Label, Multi-Center, Safety and Efficacy Study of PRT3645 in Participants With Select Advanced or Metastatic Solid Tumors
Anticipated Study Start Date :
Dec 1, 2022
Anticipated Primary Completion Date :
Dec 1, 2024
Anticipated Study Completion Date :
Dec 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: PRT3645

PRT3645 capsules will be self-administered once daily, continuously, at the dose-level assigned

Drug: PRT3645
PRT3645 capsules will be self-administered once daily, continuously, at the dose-level assigned

Outcome Measures

Primary Outcome Measures

  1. Dose limiting toxicity (DLT) of PRT3645 [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 [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 [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 [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 [Baseline through approximately 2 years]

    PRT3645 pharmacokinetics will be calculated including the maximum observed plasma concentration.

  3. Pharmacodynamic effect of PRT3645: Target engagement [Baseline through approximately 2 years]

    Pharmacodynamic effect of PRT3645 demonstrating target engagement by assessment of phosphorylation of Rb.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

  • Prelude Therapeutics

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Prelude Therapeutics
ClinicalTrials.gov Identifier:
NCT05538572
Other Study ID Numbers:
  • PRT3645-01
First Posted:
Sep 14, 2022
Last Update Posted:
Sep 14, 2022
Last Verified:
Sep 1, 2022

Study Results

No Results Posted as of Sep 14, 2022