BLU-667 in Patients With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors

Phase 1 Study of BLU-667 in Patients With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors: Conditions:   Lung Cancer, Nonsmall Cell;   Thyroid Cancer;   Solid Tumor

Intervention:   Drug: BLU-667

Sponsor:   Blueprint Medicines Corporation

Not yet recruiting - verified January 2017

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 NSCLC, thyroid cancer and other solid tumors.

Condition	Intervention	Phase
Lung Cancer, Nonsmall Cell Thyroid Cancer Solid Tumor	Drug: BLU-667	Phase 1

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: No masking Primary Purpose: Treatment
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

Resource links provided by NLM:

Genetics Home Reference related topics: lung cancer

MedlinePlus related topics: Cancer Lung Cancer Thyroid Cancer Thyroid Diseases

Drug Information available for: Thyroid

Genetic and Rare Diseases Information Center resources: Papillary Thyroid Carcinoma Thyroid Cancer, Medullary

U.S. FDA Resources 

Further study details as provided by Blueprint Medicines Corporation:

Primary Outcome Measures:

• 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 ]
• Number of patients with adverse events and serious adverse events [ Time Frame: Every cycle (28 days) for approximately 24 months or earlier if patient terminates from the study, and 30 days after the last dose ]
• Changes in clinical laboratory results [ Time Frame: Every cycle (28 days) for approximately 24 months or earlier if patient terminates from the study, and 14 days after the last dose ]
• Changes in ECG findings [ Time Frame: Every cycle (28 days) up to Cycle 4 ]

Secondary Outcome Measures:

• Maximum plasma concentration (Cmax) of BLU-667 [ Time Frame: Every cycle (28 days) up to Cycle 4 ]
• Time to maximum plasma concentration (Tmax) of BLU-667 [ Time Frame: Every cycle (28 days) up to Cycle 4 ]
• Area under the plasma concentration time curve from 0 to 24 hours (AUC0-24) and from 0 to infinity (AUCinf) of BLU-667 [ Time Frame: Every cycle (28 days) up to Cycle 4 ]
• Terminal half-life (t1/2) of BLU-667 [ Time Frame: Every cycle (28 days) up to Cycle 4 ]
• RET gene status in plasma circulating tumor deoxyribonucleic acid (ctDNA) and tumor tissue [ Time Frame: 28-day treatment Cycles 1, 2, and 3, every other cycle thereafter through the first 12 months of treatment, and 14 days after the last dose ]
• Change in blood calcitonin (medullary thyroid cancer patients) [ Time Frame: 28-day treatment Cycles 1, 2, and 3, every other cycle thereafter through the first 12 months of treatment, and 14 days after the last dose ]
• Change in tumor biomarker levels (phosphorylated SHC adaptor protein [p-SHC] and dual specificity phosphatase 6 [DUSP6] [ Time Frame: 28-day treatment Cycles 1, 2, and 3, every other cycle thereafter through the first 12 months of treatment, and 14 days after the last dose ]
• Overall response rate (ORR) [ 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 ]
  ORR is defined as the rate of complete response (CR) and partial response (PR).
• Duration of response (DOR) [ 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 ]
• Clinical benefit rate (CBR) [ 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 ]
  CBR is defined as the rate of CR, PR, and stable disease (SD).

Estimated Enrollment:	115
Anticipated Study Start Date:	March 2017
Estimated Study Completion Date:	March 2023
Estimated Primary Completion Date:	March 2021 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: BLU-667 Dose Escalation: Multiple doses of BLU-667 for oral administration. Dose Expansion: Oral dose of BLU-667 as determined during Dose Escalation.	Drug: BLU-667 BLU-667 is a potent and selective inhibitor of the RET mutations, fusions, and predicted resistant mutants

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 NSCLC, advanced thyroid cancer and other advanced solid tumors that have progressed following standard systemic therapy, have not adequately responded to standard systemic therapy, or in patients who are intolerant to or have declined standard therapy.

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