A Study of PRT2527 in Participants With Advanced Solid Tumors

Non-small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05159518
• Other study ID #: PRT2527-01
• Status: Completed
• Phase: Phase 1
• Start date: February 14, 2022
• Est. completion date: December 6, 2023

Study information

• Verified date: December 2023
• Source: Prelude Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 6, 2023
• Est. primary completion date: December 6, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Carcinoma, Non-Small-Cell Lung
• Castrate Resistant Prostate Cancer
• Non-small Cell Lung Cancer
• Prostatic Neoplasms
• Sarcoma

Intervention

Drug:
• PRT2527
PRT2527 will be administered by intravenous infusion

Locations

Country	Name	City	State
United States	Investigational Drug Services, AdventHealth Celebration	Celebration	Florida
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	Sarah Cannon Research Institute at HealthONE	Denver	Colorado
United States	NEXT Virginia	Fairfax	Virginia
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Thomas Jefferson University, Sidney Kimmel Cancer Center	Philadelphia	Pennsylvania
United States	Florida Cancer Specialists	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Prelude Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose limiting toxicities (DLT) of PRT2527	Dose limiting toxicities will be evaluated over the 21-day observation period	Baseline through Day 21
Primary	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
Primary	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	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
Secondary	Pharmacokinetic profile of PRT2527: maximum observed plasma concentration	PRT2527 pharmacokinetics will be calculated including the maximum observed plasma concentration	Baseline through approximately 1 year
Secondary	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
Secondary	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