A Study of PRT2527 in Participants With Advanced Solid Tumors

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Sarcoma, Castrate Resistant Prostate Cancer, Hormone Receptor Positive HER2 Negative Breast Cancer, Non-small Cell Lung Cancer, Solid Tumors With Known MYC Amplification

Intervention / Treatment
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* Drug: PRT2527


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Tumor types under study Selected sarcomas with a documented gene fusion Castrate resistant prostate cancer (CRPC) Hormone receptor positive (HR+), HER2 negative (HER2-) breast cancer Non-small cell lung cancer (NSCLC) 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: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRT2527<br>PRT2527 will be administered by intravenous infusion | Drug: PRT2527<br>* PRT2527 will be administered by intravenous infusion<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, Castrate Resistant Prostate Cancer, CDK9 Inhibitor, CRPC, Cyclin-dependent Kinase 9, Hormone Receptor Positive HER2 Negative Breast Cancer, HR+/HER2- Breast Cancer, Non-small Cell Lung Cancer, NSCLC, Prostate Cancer, PRT2527, Refractory Solid Tumors, Relapsed Solid Tumors, Sarcoma