A Study of PRT2527 in Patients With Advanced Solid Tumors

Sponsor

Prelude Therapeutics (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05159518

Collaborator

(none)

Enrollment

Locations

Arm

21.5

Anticipated Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 1 dose-escalation study of PRT2527, a Cyclin-dependent Kinase 9 (CDK9) inhibitor, in patients 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.

Condition or Disease	Intervention/Treatment	Phase
Ewing Sarcoma Myxoid/Round Cell Liposarcoma Synovial Sarcoma Castrate Resistant Prostate Cancer Hormone Positive Breast Cancer HER2-negative Breast Cancer Non-small Cell Lung Cancer Solid Tumors With Known MYC Amplification	Drug: PRT2527	Phase 1

Detailed Description

This is a multicenter, open-label, dose-escalation Phase 1 study of PRT2527, a CDK9 inhibitor, evaluating patients with selected advanced/metastatic sarcomas displaying a gene fusion, castrate resistant prostate cancer, hormone 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 patients per dose level; 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. The total sample size will be approximately 30 patients for MTD and RP2D determination.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 14, 2022

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: PRT2527

PRT2527 will be administered by intravenous infusion

Drug: PRT2527

PRT2527 will be administered by intravenous infusion

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Tumor types under study

Selected Sarcomas (Ewing Sarcoma; Synovial Sarcoma; Myxoid/Round Cell Liposarcoma) with a gene fusion
Castrate Resistant Prostate Cancer
Hormone Positive, HER2 Negative Breast Cancer
Advanced Non-Small Cell Lung Cancer
MYC Amplified Solid Tumors

Must have measurable disease per RECIST 1.1; patients with prostate cancer may have 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
Except for alopecia, all patients must have recovered from the effects of any prior cancer related therapy, radiotherapy, or surgery (toxicity from prior therapy is not greater than 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:

Curatively treated malignancy with no known active disease
Curatively treated non-melanoma skin cancer without evidence of disease
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sarah Cannon Research Institute at HealthONE	Denver	Colorado	United States	80218
2	Investigational Drug Services, AdventHealth Celebration	Celebration	Florida	United States	34747
3	Florida Cancer Specialists	Sarasota	Florida	United States	34232
4	Thomas Jefferson University, Sidney Kimmel Cancer Center	Philadelphia	Pennsylvania	United States	19107
5	Mary Crowley Cancer Research	Dallas	Texas	United States	75230
6	NEXT Virginia	Fairfax	Virginia	United States	22031