Clinical Trials /

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

NCT03037385

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
  • Thyroid Gland Medullary Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase 1 Study of the Highly-selective RET Inhibitor BLU-667 in Patients With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced 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

Clinical Trial IDs

  • ORG STUDY ID: BLU-667-1101
  • SECONDARY ID: 2016-004390-41
  • NCT ID: NCT03037385

Conditions

  • RET-altered Non Small Cell Lung Cancer
  • Medullary Thyroid Cancer
  • RET-altered Papillary Thyroid Cancer
  • RET-altered Colon Cancer
  • RET-altered Solid Tumors

Interventions

DrugSynonymsArms
BLU-667BLU-667

Purpose

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.

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
BLU-667ExperimentalDose Escalation: Multiple doses of BLU-667 for oral administration. Dose Expansion: Oral dose of BLU-667 as determined during Dose Escalation.
  • BLU-667

Eligibility Criteria

        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:

               1. Platelet count < 75 × 10^9/L.

               2. Absolute neutrophil count <1.0 × 10^9/L.

               3. 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.

               4. 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.

               5. Total bilirubin > 1.5 × ULN; > 3 × ULN with direct bilirubin > 1.5 × ULN in
                  presence of Gilbert's disease.

               6. Estimated (Cockcroft-Gault formula) or measured creatinine clearance <40 mL/min.

               7. 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determination of maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of BLU-667
Time Frame:Cycle 1 (28 days) of treatment for MTD and at the end of every cycle (28 days) for RP2D for approximately 12 months or earlier if patient terminates from the study
Safety Issue:
Description:As assessed by RECIST v1.1 or RANO, as appropriate per tumor type

Secondary Outcome Measures

Measure:DOR, DCR, PFS and OS
Time Frame:Approximately every 8 weeks during treatment, 14 days after the last dose, and every 3 months after the last dose (up to 2 years) in patients without progressive disease
Safety Issue:
Description:
Measure:RET gene status and correlation between RET gene status and ORR, DOR, DCR and other antineoplastic measures
Time Frame:Approximately every 8 weeks during treatment, 14 days after the last dose, and every 3 months after the last dose (up to 2 years) in patients without progressive disease
Safety Issue:
Description:
Measure:Pharmacokinetic parameters
Time Frame:Approximately every 2 weeks in Cycle 1 and monthly through Cycle 4
Safety Issue:
Description:
Measure:Pharmacodynamic parameters
Time Frame:Approximately every 2 weeks in Cycle 1 and monthly through Cycle 3 and every other month through Cycle 12
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Blueprint Medicines Corporation

Trial Keywords

  • 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

Last Updated