CAMBRIDGE, Mass., June 21, 2018 /PRNewswire/ -- Blueprint Medicines Corporation (NASDAQ: BPMC), a leader in discovering and developing targeted kinase medicines for patients with genomically defined diseases, today announced it has dosed the first patient in the VOYAGER Phase 3 clinical trial, which is evaluating the safety and efficacy of avapritinib compared to regorafenib in patients with advanced gastrointestinal stromal tumors (GIST). The VOYAGER trial is designed to enroll patients previously treated with imatinib and one or two additional tyrosine kinase inhibitors (TKIs).

"The initiation of the VOYAGER Phase 3 trial represents an important milestone for Blueprint Medicines, as we advance efforts to achieve registration of avapritinib in a broad GIST population," said Andy Boral, M.D., Ph.D., Chief Medical Officer of Blueprint Medicines. "With compelling Phase 1 clinical data showing objective responses and prolonged progression free survival in heavily pretreated patients, we believe avapritinib has the potential to offer improved disease control to patients with third-line and later advanced GIST."

Avapritinib is a potent and selective inhibitor of activated KIT and PDGFRA mutant kinases. TKIs currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of advanced GIST only bind to the inactive conformations of KIT and PDGFRA, whereas avapritinib is uniquely designed to bind and inhibit the active conformation of these protein kinases. This allows for potent inhibition of both primary and secondary mutations that shift the kinase towards its active conformation. In patients with relapsed metastatic GIST whose disease has progressed following treatment with imatinib, resistance mutations in the activation loop accumulate with higher frequency, limiting the effectiveness of approved TKIs. 

About the VOYAGER Phase 3 Clinical Trial

The VOYAGER clinical trial is a global, open-label, randomized, Phase 3 trial designed to evaluate the safety and efficacy of avapritinib versus regorafenib in patients with third- or fourth-line advanced GIST. Eligible patients will have previously received imatinib and one or two additional tyrosine kinase inhibitors. The trial is designed to enroll approximately 460 patients randomized 1:1 to receive avapritinib dosed at 300 mg once daily (QD) or regorafenib dosed at 160 mg QD for three weeks, followed by one week off, at multiple sites in the United States, European Union, Australia and Asia. Patients who are randomized to receive regorafenib and experience disease progression confirmed by central radiology review may be offered the opportunity to cross-over to the avapritinib treatment arm. The primary efficacy endpoint is progression free survival determined by central radiologic assessment per modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary endpoints include objective response rate, overall survival and quality of life outcome measures. Regorafenib, also known as Stivarga®, is an oral, multi-kinase inhibitor approved by the U.S. Food and Drug Administration for the treatment of patients with third-line GIST.

Patients and physicians interested in the VOYAGER Phase 3 trial can contact the Blueprint Medicines study director at studydirector@blueprintmedicines.com or 1-617-714-6707. For more information about the VOYAGER trial, please visit www.voyagertrial.com. Additional details are also available on www.clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT03465722).

About Avapritinib

Avapritinib is an orally available, potent and highly selective inhibitor of KIT and PDGFRA. In certain diseases, a spectrum of clinically relevant mutations forces the KIT or PDGFRA protein kinases into an increasingly active state. Avapritinib is uniquely designed to bind and inhibit the active conformation of these proteins, including PDGFRα D842V and KIT D816V at sub-nanomolar potency. Blueprint Medicines is initially developing avapritinib, an investigational medicine, for the treatment of patients with advanced GIST and systemic mastocytosis.

In June 2017, avapritinib received Breakthrough Therapy Designation from the FDA for the treatment of patients with unresectable or metastatic GIST harboring the PDGFRα D842V mutation. Previously, the FDA granted orphan drug designation to avapritinib for GIST and mastocytosis and fast track designation to avapritinib for GIST. In addition, the European Commission has granted orphan drug designation to avapritinib for GIST. In May 2018, Blueprint Medicines announced plans to submit a New Drug Application to the FDA for avapritinib for the treatment of PDGFRα D842V-driven GIST in the first half of 2019. In June 2018, Blueprint Medicines announced an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of avapritinib and certain other drug candidates in Mainland China, Hong Kong, Macau and Taiwan.

About GIST

GIST is a sarcoma, or tumor of bone or connective tissue, of the gastrointestinal (GI) tract. Tumors arise from cells in the wall of the GI tract and occur most often in the stomach or small intestine. Most patients are diagnosed between the ages of 50-80, and diagnosis is typically triggered by GI bleeding, incidental findings during surgery or imaging and, in rare cases, tumor rupture or GI obstruction.

Most GIST cases are caused by a spectrum of clinically relevant mutations that force the KIT or PDGFRA protein kinases into an increasingly active state. In addition, resistance mutations in the activation loop accumulate with higher frequency in heavily pretreated patients. Because currently available therapies only bind to the inactive protein conformations, certain primary and secondary mutations typically lead to treatment resistance and disease progression.

Treatment options for KIT-driven GIST patients whose disease progresses or develops resistance are currently limited, with approved therapies providing a progression free survival of up to six months and a response rate between five percent and seven percent. There are no effective treatment options for patients with PDGFRα D842V-driven GIST, and progression often occurs in as little as three months with available treatment options.

About Blueprint Medicines

Blueprint Medicines is developing a new generation of targeted and potent kinase medicines to improve the lives of patients with genomically defined diseases. Its approach is rooted in a deep understanding of the genetic blueprint of cancer and other disease driven by the abnormal activation of kinases. Blueprint Medicines is advancing multiple programs in clinical development for subsets of patients with gastrointestinal stromal tumors, hepatocellular carcinoma, systemic mastocytosis, non-small cell lung cancer, medullary thyroid cancer and other advanced solid tumors, as well as multiple programs in research and preclinical development. For more information, please visit www.blueprintmedicines.com.

Cautionary Notes Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding plans for achieving registration of avapritinib in a broad GIST population; expectations regarding the potential benefits of avapritinib in treating patients with GIST, including patients with third-line and later advanced GIST; and Blueprint Medicines' strategy, business plans and focus. The words "may," "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," "estimate," "predict," "project," "potential," "continue," "target" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks and uncertainties related to the delay of any current or planned clinical trials or the development of Blueprint Medicines' drug candidates, including avapritinib, BLU-554, BLU-667 and BLU-782; Blueprint Medicines' advancement of multiple early-stage efforts; Blueprint Medicines' ability to successfully demonstrate the safety and efficacy of its drug candidates; the preclinical and clinical results for Blueprint Medicines' drug candidates, which may not support further development of such drug candidates; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials; Blueprint Medicines' ability to develop and commercialize companion diagnostic tests for its current and future drug candidates, including companion diagnostic tests for BLU-554 for FGFR4-driven hepatocellular carcinoma, avapritinib for PDGFRα D842V-driven GIST and BLU-667 for RET-driven non-small cell lung cancer; the success of Blueprint Medicines' current and future collaborations, including its cancer immunotherapy collaboration with F. Hoffmann-La Roche Ltd and Hoffmann-La Roche Inc. and its collaboration with CStone Pharmaceuticals. These and other risks and uncertainties are described in greater detail in the section entitled "Risk Factors" in Blueprint Medicines' Quarterly Report on Form 10-Q for the quarter ended March 31, 2018, as filed with the Securities and Exchange Commission (SEC) on May 2, 2018, and any other filings that Blueprint Medicines has made or may make with the SEC in the future. Any forward-looking statements contained in this press release represent Blueprint Medicines' views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Except as required by law, Blueprint Medicines explicitly disclaims any obligation to update any forward-looking statements.

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SOURCE Blueprint Medicines

Kristin Hodous, 617-714-6674, KHodous@blueprintmedicines.com; Jim Baker, 617-844-8236, JBaker@blueprintmedicines.com