A Study of PRT2527 in Participants With Advanced Solid Tumors

Phase 1

Completed

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

• Registration Number: NCT05159518
• Lead Sponsor: Prelude Therapeutics

Brief Summary

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.

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 Timeline

• Study First Submitted: 2021-12-02
• Study First Submitted QC: 2021-12-02
• Study First Posted: 2021-12-16
• Study Start: 2022-02-14
• Status Verified: 2023-12
• Primary Completion: 2023-12-06
• Study Completion: 2023-12-06
• Last Update Submitted: 2023-12-08
• Last Update Posted: 2023-12-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
PRT2527	PRT2527	PRT2527 will be administered by intravenous infusion

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Safety and tolerability of PRT2527: AEs, SAEs, CTCAE assessments	Baseline through approximately 2 years	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)
Pharmacokinetic profile of PRT2527: maximum observed plasma concentration	Baseline through approximately 1 year	PRT2527 pharmacokinetics will be calculated including the maximum observed plasma concentration
Anti-tumor activity of PRT2527: measurement of objective responses	Baseline through approximately 2 years	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
Duration of response to PRT2527: Objective responses	Baseline through approximately 2 years	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

Trial Locations

Locations (8)

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Mary Crowley Cancer Research; 🇺🇸 Dallas, Texas, United States

Sarah Cannon Research Institute at HealthONE; 🇺🇸 Denver, Colorado, United States

Florida Cancer Specialists; 🇺🇸 Sarasota, Florida, United States

Thomas Jefferson University, Sidney Kimmel Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Fox Chase Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

NEXT Virginia; 🇺🇸 Fairfax, Virginia, United States

Investigational Drug Services, AdventHealth Celebration; 🇺🇸 Celebration, Florida, United States