Phase 1 / 2 Study of the Highly-selective RET Inhibitor, Pralsetinib (BLU-667), in Patients With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors

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Status: Active

Description

This is a Phase 1 / 2, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antineoplastic activity of pralsetinib (BLU-667) administered orally in patients with medullary thyroid cancer, RET-altered NSCLC and other RET-altered solid tumors.

Eligibility Criteria

Inclusion Criteria

  • Diagnosis during dose escalation (Phase 1) - Pathologically documented, definitively diagnosed non-resectable advanced solid tumor.
  • All patients treated at doses > 120 mg per day must have medullary thyroid cancer (MTC), or a RET-altered solid tumor per local assessment of tumor tissue and/or blood.
  • Diagnosis during dose expansion (Phase 2) - All patients (with the exception of Groups 3 and 4) must have an oncogenic RET-rearrangement/fusion or mutation (excluding synonymous, frameshift, and nonsense mutations) solid tumor, as determined by local or central testing of tumor or circulating tumor nucleic acid in blood; as detailed below.
  • Group 1 - patients must have pathologically documented, definitively diagnosed locally advanced or metastatic NSCLC with a RET fusion previously treated with a platinum-based chemotherapy.
  • Group 2 - patients must have pathologically documented, definitively diagnosed locally advanced or metastatic NSCLC with a RET fusion not previously treated with a platinum-based chemotherapy, including those who have not had any systemic therapy. Prior platinum chemotherapy in the neoadjuvant and adjuvant setting is permitted if the last dose of platinum was 4 months or more before the first dose of study drug.
  • Group 3 - patients must have pathologically documented, definitively diagnosed advanced MTC that has progressed within 14 months prior to the Screening Visit and was previously treated with cabozantinib and/or vandetanib.
  • Group 4 - patient must have pathologically documented, definitively diagnosed advanced MTC that has progressed within 14 months prior to the Screening Visit and was not previously treat with cabozantinib and/or vandetanib.
  • Group 5 -patients must have a pathologically documented, definitively diagnosed advanced solid tumor with an oncogenic RET fusion previously treated with SOC appropriate for the tumor type and not eligible for any of the other groups.
  • Group 6 - patients must have a pathologically documented, definitively diagnosed advanced solid tumor with an oncogenic RET fusion or mutation that was previously treated with a selective TKI that inhibits RET
  • Group 7 - patients must have a pathologically documented, definitively diagnosed advanced solid tumor with an oncogenic RET mutation previously treated with SOC appropriate for the tumor type and not eligible for any of the other groups
  • Patients must have non-resectable disease. Phase 1 only patients must have progressed following standard therapy or have not adequately responded to standard therapy, or the patient must be intolerant to, or the Investigator has determined that treatment with standard therapy is not appropriate, or there must be no accepted standard therapy for their disease.
  • Patient has Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1.

Exclusion Criteria

  • Patient's cancer has a known primary driver alteration other than RET. For example, NSCLC with a targetable mutation in EGFR, ALK, ROS1 or BRAF; colorectal with an oncogenic KRAS, NRAS, or BRAF mutation.
  • Patient has any of the following within 14 days prior to the first dose of study drug:
  • Platelet count < 75 × 10^9/L.
  • Absolute neutrophil count <1.0 × 10^9/L.
  • Hemoglobin < 9.0 g/dL (red blood cell transfusion and erythropoietin may be used to reach at least 9.0 g/dL, but must have been administered at least 2 weeks prior to the first dose of study drug.
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 × the upper limit of normal (ULN) if no hepatic metastases are present; >5 × ULN if hepatic metastases are present.
  • Total bilirubin > 1.5 × ULN; > 3 × ULN with direct bilirubin > 1.5 × ULN in presence of Gilbert's disease.
  • Estimated (Cockcroft-Gault formula) or measured creatinine clearance <40 mL/min.
  • Total serum phosphorus >5.5 mg/dL
  • QT interval corrected using Fridericia's formula (QTcF) >470 msec or history of prolonged QT syndrome or Torsades de pointes, or familial history of prolonged QT syndrome.
  • Clinically significant, uncontrolled, cardiovascular disease.
  • Central nervous system (CNS) metastases or a primary CNS tumor that is associated with progressive neurological symptoms.
  • Clinically symptomatic interstitial lung disease or interstitial pneumonitis including radiation pneumonitis
  • Patients in Groups 1-5 and 7 (Phase 2) previously treated with a selective RET inhibitor

Locations & Contacts

Arizona

Phoenix
Mayo Clinic Hospital
Status: Active
Name Not Available
Scottsdale
Mayo Clinic in Arizona
Status: Active
Name Not Available

California

Orange
UC Irvine Health / Chao Family Comprehensive Cancer Center
Status: Active
Name Not Available

Colorado

Aurora
University of Colorado Hospital
Status: Active
Name Not Available

District of Columbia

Washington
MedStar Georgetown University Hospital
Status: Active
Name Not Available

Florida

Jacksonville
Mayo Clinic in Florida
Status: Active
Name Not Available
Miami
University of Miami Miller School of Medicine-Sylvester Cancer Center
Status: Active
Name Not Available

Massachusetts

Boston
Beth Israel Deaconess Medical Center
Status: Approved
Name Not Available
Massachusetts General Hospital Cancer Center
Status: Active
Name Not Available

Michigan

Ann Arbor
University of Michigan Comprehensive Cancer Center
Status: Approved
Name Not Available

Minnesota

Rochester
Mayo Clinic
Status: Active
Name Not Available

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: Active
Name Not Available

Oregon

Portland
OHSU Knight Cancer Institute
Status: Active
Name Not Available

Pennsylvania

Philadelphia
University of Pennsylvania / Abramson Cancer Center
Status: Active
Name Not Available

Texas

Houston
M D Anderson Cancer Center
Status: Active
Name Not Available

Washington

Seattle
Fred Hutch / University of Washington Cancer Consortium
Status: Active
Name Not Available

Trial Objectives and Outline

The study consists of 2 parts, a dose-escalation part (Phase 1) and an expansion part (Phase 2). Both parts will enroll patients with advanced non-resectable NSCLC, advanced non-resectable thyroid cancer and other advanced solid tumors that have progressed following standard systemic therapy, have not adequately responded to standard systemic therapy, or the patients must be intolerant to or the Investigator has determined that treatment with standard therapy is not appropriate, or there must be no accepted standard therapy for their disease.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
Blueprint Medicines Corporation

Trial IDs

Primary ID BLU-667-1101
Secondary IDs NCI-2017-00300, 2016-004390-41
Clinicaltrials.gov ID NCT03037385