Blueprint Medicines Announces Proof-of-Concept Data Showing Combination of BLU-667 and Osimertinib Overcame Treatment Resistance in Two Patients with EGFR-Mutant, Non-Small Cell Lung Cancer and an Acquired RET Fusion
"The combination of two highly selective agents ― BLU-667 and osimertinib ― has the potential to become an important new tool to overcome treatment resistance in a subset of patients with EGFR-mutant, non-small cell lung cancer," said
BLU-667 is an investigational precision therapy designed to potently and selectively inhibit RET alterations including resistance mutations. It is currently being evaluated in the global Phase 1 ARROW clinical trial in patients with RET-altered NSCLC, medullary thyroid cancer (MTC) and other solid tumors.
The WCLC presentation and Cancer Discovery article included preclinical data and two clinical cases highlighting the potential of combining BLU-667 and osimertinib to overcome treatment resistance in EGFR-mutant NSCLC.
The clinical cases included two patients treated with BLU-667 and osimertinib under investigator-sponsored protocols. The patients had advanced EGFR-mutant NSCLC that progressed on standard targeted therapy, with an acquired RET fusion identified via lung biopsy. Radiographic scans after eight weeks showed both patients experienced a partial response (both pending confirmation), with each achieving a 78 percent reduction in target tumors per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The combination was well tolerated, and all reported adverse events were Grade 1 or 2. Both patients continue to receive treatment as of
Based on these data,
The paper, titled, "Landscape of acquired resistance to osimertinib in EGFR-mutant NSCLC and clinical validation of combined EGFR and RET inhibition with osimertinib and BLU-667 for acquired RET fusion," will be published online in Cancer Discovery at
About RET-Altered Solid Tumors
RET activating fusions and mutations are a key disease driver in many cancer types, including NSCLC and MTC. RET fusions are implicated in approximately 1 to 2 percent of patients with NSCLC, while RET mutations are implicated in approximately 60 percent of patients with MTC. In addition, oncogenic RET alterations are observed at low frequencies in colorectal, breast, pancreatic and other cancers, and RET fusions have been observed in patients with treatment-resistant, EGFR-mutant NSCLC.
Currently, there are no approved therapies that selectively target RET-driven cancers, though there are several approved multi-kinase inhibitors with RET activity being evaluated in clinical trials. Thus far, clinical activity attributable to RET inhibition has been uncertain for these inhibitors, likely due to insufficient inhibition of RET and off-target toxicities. There is a need for precision therapies that provide durable clinical benefit by selectively targeting RET alterations and resistance mutations.
BLU-667 is an investigational, once-daily oral precision therapy specifically designed for highly potent and selective targeting of oncogenic RET fusions, mutations and resistance mutations. In preclinical studies, BLU-667 consistently demonstrated sub-nanomolar potency against the most common RET fusions, activating mutations and resistance mutations. In addition, BLU-667 demonstrated markedly improved selectivity for RET compared to approved multi-kinase inhibitors, including more than 80-fold improved potency for RET versus VEGFR2. By suppressing primary and secondary mutants, BLU-667 has the potential to overcome and prevent the emergence of clinical resistance. This approach is expected to enable durable clinical responses across the range of RET alterations, with a favorable safety profile.
Patients and physicians interested in the ARROW clinical trial can contact the
BLU-667 was discovered by Blueprint Medicine's research team based on its proprietary compound library. The company is developing BLU-667 for the treatment of people with RET-altered NSCLC, MTC and other solid tumors.
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 Note 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 and timelines for the clinical development of BLU-667, including plans to explore opportunities to evaluate the combination of BLU-667 and osimertinib in additional patients with treatment-resistant, EGFR-mutant NSCLC harboring a RET fusion; expectations regarding the potential benefits of BLU-667 in treating patients with RET-altered cancers, including patients with treatment-resistant, EGFR-mutant NSCLC; expectations regarding the potential benefits of treatment with BLU-667 in combination with other therapies, including osimertinib; and
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Investor Relations Contact: Kristin Hodous, 617-714-6674, KHodous@blueprintmedicines.com; Media Relations Contact: Andrew Law, 617-844-8205, ALaw@blueprintmedicines.com