Castrate Resistant Prostate Cancer, Hormone Receptor Positive HER2 Negative Breast Cancer, Non-small Cell Lung Cancer, Sarcoma, Solid Tumors With Known MYC Amplification
Conditions
Keywords
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
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.
Interventions
DRUGPRT2527
PRT2527 will be administered by intravenous infusion
Sponsors
Prelude Therapeutics
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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 |
| 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 |
Countries
United States
Outcome results
None listed