A Study of PRT2527 in Participants With Advanced Solid Tumors

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

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.

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.

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.