Clinical trial NCT05159518: A Study of PRT2527 in Participants With Advanced Solid Tumors
Official title: A Phase 1, Open-Label, Multicenter, Dose Escalation and Confirmation Study of PRT2527 in Participants With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Sarcoma
Castrate Resistant Prostate Cancer
Hormone Receptor Positive HER2 Negative Breast Cancer
Non-small Cell Lung Cancer
Solid Tumors With Known MYC Amplification
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
Lead sponsor: Prelude Therapeutics
Sponsor class: INDUSTRY
First posted: 2021-12-16
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Dose limiting toxicities (DLT) of PRT2527
timeFrame: Baseline through Day 21
measure: Maximally tolerated dose (MTD) of PRT2527
timeFrame: Baseline through approximately 1 year
measure: Recommended phase 2 dose (RP2D) and schedule of PRT2527
timeFrame: Baseline through approximately 1 year
Secondary outcomes:
measure: Safety and tolerability of PRT2527: AEs, SAEs, CTCAE assessments
timeFrame: Baseline through approximately 2 years
measure: Pharmacokinetic profile of PRT2527: maximum observed plasma concentration
timeFrame: Baseline through approximately 1 year
measure: Anti-tumor activity of PRT2527: measurement of objective responses
timeFrame: Baseline through approximately 2 years
measure: Duration of response to PRT2527: Objective responses
timeFrame: Baseline through approximately 2 years
Other outcomes:
Locations:
city: Denver
country: United States
facility: Sarah Cannon Research Institute at HealthONE
state: Colorado
city: Celebration
country: United States
facility: Investigational Drug Services, AdventHealth Celebration
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Philadelphia
country: United States
facility: Thomas Jefferson University, Sidney Kimmel Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Fairfax
country: United States
facility: NEXT Virginia
state: Virginia
Study officials:
References: