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

Breast Cancer Clinical Trial

Official title:

A Phase 1 Open-Label, Multi-Center, Safety and Efficacy Study of PRT3645 in Participants With Select Advanced or Metastatic Solid Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05538572
• Other study ID #: PRT3645-01
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: December 27, 2022
• Est. completion date: December 2024

Study information

• Verified date: January 2024
• Source: Prelude Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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), malignant mesothelioma, and endometrial cancer. 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 22
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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- or HR+ and HER2+ breast cancer

2. Recurrent GBM (IDH wild type) or CDKN2A/B homozygous deleted IDH-mutant astrocytoma

3. KRAS-mutant or SMARCA4 loss 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

5. Estrogen receptor positive with TP53 wild type endometrial cancer

• 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 or Karnofsky Performance Status (KPS) =80% (KPS is for GBM only)
• 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 except for GBM.
• Endometrial cancer patients who had received prior treatment with a CDK 4/6 inhibitor.

Related Conditions & MeSH terms

• Breast Cancer
• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Squamous Cell
• Endometrial Cancer
• Endometrial Neoplasms
• Glioblastoma
• Head and Neck Squamous Cell Carcinoma
• Malignant Mesothelioma
• Mesothelioma
• Mesothelioma, Malignant
• Non-small Cell Lung Cancers
• Sarcoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

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

Locations

Country	Name	City	State
Singapore	National Cancer Centre Singapore	Singapore
United States	Winship Cancer Institute, Emory University	Atlanta	Georgia
United States	AdventHealth Medical Group Oncology Research at Celebration	Celebration	Florida
United States	Cleveland Clinic	Cleveland	Ohio
United States	NEXT Virginia	Fairfax	Virginia
United States	Miami Cancer Institute	Miami	Florida
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Smilow Cancer Hospital Phase 1 Unit	New Haven	Connecticut
United States	Laura and Isaac Perlmutter Cancer Center/ NYU Langone Health	New York	New York
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Thomas Jefferson University, Sidney Kimmel Cancer Center	Philadelphia	Pennsylvania
United States	South Texas Accelerated Research Therapeutics, LLC	San Antonio	Texas
United States	Florida Cancer Specialists	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Prelude Therapeutics

Countries where clinical trial is conducted

United States,  Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose limiting toxicity (DLT) of PRT3645	Dose limiting toxicity will be evaluated over the 28-day observation period	Baseline through Day 28
Primary	Safety and tolerability of PRT3645: AEs, CTCAE Assessments	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.	Baseline through approximately 2 years
Primary	Maximally tolerated dose (MTD)/Recommended phase 2 dose (RP2D) of PRT3645	The MTD/RP2D will be established for further investigation in participants with advanced solid tumors	Baseline through approximately 2 years
Secondary	Efficacy of PRT3645: Tumor assessment and responses	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.	Baseline through approximately 2 years
Secondary	Pharmacokinetic profile of PRT3645: Minimum and maximum observed plasma concentration	PRT3645 pharmacokinetics will be calculated including the minimum and maximum observed plasma concentration.	Baseline through approximately 2 years
Secondary	Pharmacodynamic effect of PRT3645: Target engagement	Pharmacodynamic effect of PRT3645 demonstrating target engagement by assessment of phosphorylation of Rb.	Baseline through approximately 2 years