A Study of PRT2527 in Participants With Advanced Solid Tumors

A Phase 1, Open-Label, Multicenter, Dose Escalation and Confirmation Study of PRT2527 in Participants With Advanced Solid Tumors

This is a Phase 1 dose-escalation and confirmation study of PRT2527, a Cyclin-dependent Kinase 9 (CDK9) inhibitor, in participants with advanced solid tumors. The purpose of this study is to define the dosing schedule, and maximally tolerated dose to be used in subsequent development of PRT2527.

Study Overview

• Status: Completed
• Conditions: Sarcoma; Non-small Cell Lung Cancer; Castrate Resistant Prostate Cancer; Solid Tumors With Known MYC Amplification; Hormone Receptor Positive HER2 Negative Breast Cancer
• Intervention / Treatment: Drug: PRT2527

Detailed Description

This is a multicenter, open-label, dose-escalation and confirmation Phase 1 study of PRT2527, a CDK9 inhibitor, evaluating participants with selected advanced/metastatic sarcomas displaying a documented gene fusion, castrate resistant prostate cancer, hormone receptor positive HER2-negative breast cancer, advanced/metastatic non-small cell lung cancer, and solid tumors displaying MYC amplification. The study plan expects to evaluate approximately six dose levels of approximately 1-6 participants per dose level; however additional and/or intermediate 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. The total sample size will be approximately 30 patients for MTD and RP2D determination.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Sarah Cannon Research Institute at HealthONE
  • Florida
    • Celebration, Florida, United States, 34747
      • Investigational Drug Services, AdventHealth Celebration
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Specialists
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University, Sidney Kimmel Cancer Center
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • NEXT Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Tumor types under study

  1. Selected sarcomas with a documented gene fusion
  2. Castrate resistant prostate cancer (CRPC)
  3. Hormone receptor positive (HR+), HER2 negative (HER2-) breast cancer
  4. Non-small cell lung cancer (NSCLC)
  5. MYC amplified solid tumors
• Must have measurable disease per RECIST 1.1; participants with CRPC or sarcoma may have nonmeasurable but evaluable disease
• Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1
• Adequate organ function
• Must provide tumor tissue sample to the central laboratory for biomarker analysis
• Participants must have recovered from the effects of prior cancer-related therapy, radiotherapy, or surgery to ≤ Grade 1

Exclusion Criteria:

• Primary malignancies of the CNS, or uncontrolled CNS metastases, including impending spinal cord compression
• have a corrected QT interval >480 msec from prior or baseline
• have impaired cardiac function or clinically significant cardiac disease
• Treatment with strong inhibitors or inducers of CYP3A4
• Prior exposure to a CDK9 inhibitor

• History of another malignancy except for:

  1. Curatively treated malignancy with no known active disease
  2. Curatively treated non-melanoma skin cancer without evidence of disease
  3. Curatively treated carcinoma in situ without evidence of disease
• have undergone major surgery within 2 weeks prior to Week 1 Day 1
• have had chemotherapy, biologic therapy, targeted therapy, immunotherapy, extended-field radiotherapy, or investigational agents within 5 half-lives or 28 days (whichever is shorter) prior to administration of the first dose of study drug on Week 1 Day 1.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PRT2527; PRT2527 will be administered by intravenous infusion	Drug: PRT2527; PRT2527 will be administered by intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose limiting toxicities (DLT) of PRT2527	Dose limiting toxicities will be evaluated over the 21-day observation period	Baseline through Day 21
Maximally tolerated dose (MTD) of PRT2527	The MTD will be established for further investigation in participants with advanced solid tumors	Baseline through approximately 1 year
Recommended phase 2 dose (RP2D) and schedule of PRT2527	The RP2D will be established for further investigation in participants with advanced solid tumors	Baseline through approximately 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of PRT2527: AEs, SAEs, CTCAE assessments	Safety and tolerability will be assessed by recording adverse events (AEs) and serious adverse events (SAEs) according to Common Terminology Criteria for Adverse Events (CTCAE)	Baseline through approximately 2 years
Pharmacokinetic profile of PRT2527: maximum observed plasma concentration	PRT2527 pharmacokinetics will be calculated including the maximum observed plasma concentration	Baseline through approximately 1 year
Anti-tumor activity of PRT2527: measurement of objective responses	Anti-tumor activity of PRT2527 based on the measurement of objective responses to PRT2527 according to the disease-specific response criteria for patients with advanced solid tumors	Baseline through approximately 2 years
Duration of response to PRT2527: Objective responses	Duration of response will be calculated for all patients eligible for response determination from the time that a response is first observed until progression or death, whichever occurs first	Baseline through approximately 2 years

Collaborators and Investigators

• Sponsor: Prelude Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2022
• Primary Completion (Actual): December 6, 2023
• Study Completion (Actual): December 6, 2023

Study Registration Dates

• First Submitted: December 2, 2021
• First Submitted That Met QC Criteria: December 2, 2021
• First Posted (Actual): December 16, 2021

Study Record Updates

• Last Update Posted (Estimated): December 11, 2023
• Last Update Submitted That Met QC Criteria: December 8, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Breast Cancer; NSCLC; Prostate Cancer; Sarcoma; Non-small Cell Lung Cancer; CRPC; Refractory Solid Tumors; Castrate Resistant Prostate Cancer; Cyclin-dependent Kinase 9; CDK9 Inhibitor; PRT2527; Relapsed Solid Tumors; HR+/HER2- Breast Cancer; Hormone Receptor Positive HER2 Negative Breast Cancer
• Additional Relevant MeSH Terms: Skin Diseases; Respiratory Tract Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Breast Diseases; Prostatic Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Sarcoma; Breast Neoplasms; Prostatic Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: PRT2527-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No