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



Status:Recruiting
Conditions:Lung Cancer, Lung Cancer, Colorectal Cancer, Cancer, Cancer, Cancer, Endocrine, Thyroid Cancer
Therapuetic Areas:Endocrinology, Oncology
Healthy:No
Age Range:18 - Any
Updated:3/21/2019
Start Date:March 17, 2017
End Date:March 2023
Contact:Blueprint Medicines
Email:studydirector@blueprintmedicines.com
Phone:617-714-6707

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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

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.

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.

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
We found this trial at
17
sites
4201 Belfort Road
Jacksonville, Florida 32216
(408) 293-2336
Mayo Clinic Mayo Clinic's campus in Arizona provides medical care for thousands of people from...
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185 Cambridge Street
Boston, Massachusetts 02114
617-724-5200
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Boston, MA
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3181 Southwest Sam Jackson Park Road
Portland, Oregon 97239
503 494-8311
Oregon Health and Science University In 1887, the inaugural class of the University of Oregon...
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Portland, OR
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500 S State St
Ann Arbor, Michigan 48109
(734) 764-1817
University of Michigan The University of Michigan was founded in 1817 as one of the...
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Aurora, Colorado 80045
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Bordeaux,
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Bordeaux,
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1515 Holcombe Blvd
Houston, Texas 77030
 713-792-2121
University of Texas M.D. Anderson Cancer Center The mission of The University of Texas MD...
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New York, New York 10021
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Orange, California 92868
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Philadelphia, Pennsylvania 19104
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Philadelphia, PA
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5777 East Mayo Boulevard
Phoenix, Arizona 85054
(480) 515-6296
Mayo Clinic Mayo Clinic's campus in Arizona provides medical care for thousands of people from...
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Rochester, Minnesota 55905
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Saint Louis, MO
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3800 Reservoir Rd NW
Washington, District of Columbia 20007
(202) 687-7695
Georgetown University Medical Center Georgetown University Medical Center is committed to excellence in research, education...
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