Summary

for people ages 18 years and up (full criteria)
at UC Irvine
study started
estimated completion

Description

Summary

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

Official Title

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

Details

The study consists of 2 parts, a dose-escalation part (Part 1) and an expansion part (Part 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.

Keywords

RET-altered Non Small Cell Lung Cancer Medullary Thyroid Cancer RET-altered Papillary Thyroid Cancer RET-altered Colon Cancer RET-altered Solid Tumors RET Lung RET Thyroid RET fusion RET alteration RET mutation RET positive RET inhibitor RET altered RET rearrangement RET NSCLC RET medullary thyroid cancer RET-rearranged NSCLC RET-rearranged thyroid M918T TRIM33-RET RET fusion lung cancer RET fusion thyroid cancer lung cancer mutation BLUE 667 RET tyrosine kinase RET gene mutation RET kinase RET MTC advanced lung cancer advanced non small cell lung cancer metastatic lung cancer KIF5B-RET CCDC6-RET NCOA4-RET advance solid tumor V804L V804M thyroid cancer RET inhibitor lung cancer RET inhibitor RET PTC rearranged during transfection Lung Neoplasms Carcinoma, Non-Small-Cell Lung Thyroid Diseases Thyroid Neoplasms Carcinoma Carcinoma, Neuroendocrine BLU-667

Eligibility

For people ages 18 years and up

Key Inclusion Criteria:

  • Diagnosis during dose escalation (Part 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 (Part 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.
  • 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, definitely 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, definitely 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
  • Patient must have non-resectable disease that has progressed following standard therapy or has 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.

Key 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 × 109/L.

  • Absolute neutrophil count <1.0 × 109/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 (Part 2) previously treated with a selective RET inhibitor

Locations

  • UC Irvine Medical Center accepting new patients
    Orange California 92868 United States
  • Mayo Clinic accepting new patients
    Phoenix Arizona 85054 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Blueprint Medicines Corporation
Links
More information about the study
ID
NCT03037385
Phase
Phase 1
Study Type
Interventional
Last Updated