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

NCT05538572 | Completed Phase 1 FDA Drug

• 1 other identifier: PRT3645-01
• Study Type: interventional
• Target: 22
• Locations: 2 countries
• Sites: 13

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.

Conditions

Breast Cancer; Glioblastoma; Head and Neck Squamous Cell Carcinoma; Malignant Mesothelioma; Non-small Cell Lung Cancers; Sarcoma; Endometrial Cancer

Keywords

Advanced Solid Tumors; Breast Cancer; CDK4/6; Cyclin-dependent Kinase 4; Cyclin-dependent Kinase 6; Glioblastoma; Head and Neck Squamous Cell Carcinoma; HNSCC; Malignant Mesothelioma; Metastatic Solid Tumors; Non-small Cell Lung Cancers; NSCLC; PRT3645; Sarcoma; Endometrial Cancer

Outcome Measures

Primary Outcomes (3)

• Dose limiting toxicity (DLT) of PRT3645

  Dose limiting toxicity will be evaluated over the 28-day observation period

  Baseline through Day 28

• 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

• 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 Outcomes (3)

• Efficacy of PRT3645: Tumor assessment and responses

  Baseline through approximately 2 years

• Pharmacokinetic profile of PRT3645: Minimum and maximum observed plasma concentration

  Baseline through approximately 2 years

• Pharmacodynamic effect of PRT3645: Target engagement

  Baseline through approximately 2 years

Study Arms (1)

PRT3645

EXPERIMENTAL

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

Drug: PRT3645

Interventions

PRT3645 DRUG

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

PRT3645

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed advanced, recurrent, or metastatic solid tumor malignancy that have either progress or ineligible for standard of care therapy:
• HR+ and HER2- or HR+ and HER2+ breast cancer
• Recurrent GBM (IDH wild type) or CDKN2A/B homozygous deleted IDH-mutant astrocytoma
• KRAS-mutant or SMARCA4 loss NSCLC
• 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
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Prelude Therapeutics: lead

Study Sites (13)

Smilow Cancer Hospital Phase 1 Unit

New Haven, Connecticut, 06511, United States

Location

AdventHealth Medical Group Oncology Research at Celebration

Celebration, Florida, 34747, United States

Location

Miami Cancer Institute

Miami, Florida, 33176, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322, United States

Location

Laura and Isaac Perlmutter Cancer Center/ NYU Langone Health

New York, New York, 10016, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University, Sidney Kimmel Cancer Center

Philadelphia, Pennsylvania, 19107, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, 78229, United States

Location

NEXT Virginia

Fairfax, Virginia, 22031, United States

Location

National Cancer Centre Singapore

Singapore, 168583, Singapore

Location

MeSH Terms

Conditions

Breast Neoplasms; Glioblastoma; Squamous Cell Carcinoma of Head and Neck; Mesothelioma, Malignant; Sarcoma; Endometrial Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Carcinoma, Squamous Cell; Carcinoma; Head and Neck Neoplasms; Mesothelioma; Adenoma; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplasms, Connective and Soft Tissue; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2022
• First Posted: September 14, 2022
• Study Start: December 27, 2022
• Primary Completion: June 26, 2024
• Study Completion: June 26, 2024
• Last Updated: July 1, 2024

Record last verified: 2024-06

Locations

US (12); SG (1)