Blueprint Medicines Reports ARROW Trial Data at ESMO Virtual Congress 2020 Demonstrating Durable Clinical Benefits of GAVRETO™ (Pralsetinib) in Patients with Advanced RET-Mutant Medullary Thyroid Cancer
"For patients with RET-mutant medullary thyroid cancer, there is an important need for targeted therapies like pralsetinib (GAVRETO) that are highly active across RET genotypes, including gatekeeper resistance mutations," said
"By selectively inhibiting RET alterations, GAVRETO has broad potential to address the limitations of multi-kinase inhibitors and enable transformative outcomes for patients with RET-mutant medullary thyroid cancer," said
As previously announced, the
In addition,
GAVRETO is being jointly commercialized by
Highlights from the ARROW Trial in Patients with RET-Mutant MTC
The presented data included response-evaluable patients with RET-mutant MTC who were previously treated with cabozantinib or vandetanib, or naïve to systemic treatment. Tumor response was assessed by blinded, independent central review using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. All patients received a GAVRETO starting dose of 400 mg once daily (QD), and results were reported as of a data cutoff date of
GAVRETO demonstrated broad clinical activity in patients with RET-mutant MTC with or without prior systemic therapy. In 53 patients previously treated with cabozantinib or vandetanib, the overall response rate (ORR) was 60 percent (95% CI: 46%, 74%) with one response pending confirmation, and the disease control rate (DCR) was 96 percent (95% CI: 87%, 100%). The median duration of response (DOR) was not reached (95% CI: not reached, not reached), with 94 percent of responders remaining on treatment. The median progression-free survival (PFS) was not reached (95% CI: not reached, not reached) in patients previously treated with cabozantinib or vandetanib.
In 19 systemic treatment-naïve patients who were ineligible for standard therapy per the study protocol, the confirmed ORR was 74 percent (95% CI: 49%, 91%), and the DCR was 100 percent (95% CI: 82%, 100%). The median DOR was not reached (95% CI: 7 months, not reached), with 93 percent of responders remaining on treatment. The median PFS was not reached (95% CI: not reached, not reached) in systemic treatment-naïve patients.
Five of six patients whose tumors had a RET V804M or V804L gatekeeper mutation achieved a clinical response. Three patients previously treated with multi-kinase inhibitors had a RET M918T activating mutation and a RET V804M or V804L gatekeeper resistance mutation at baseline, and all three of these patients had a clinical response following GAVRETO treatment.
The reported safety data included a total of 438 patients enrolled in the ARROW trial at a GAVRETO starting dose of 400 mg QD, regardless of tumor type. GAVRETO was well-tolerated with safety results consistent with previously reported data. Overall, treatment-related adverse events (AEs) were primarily Grade 1 or 2. The most common treatment-related AEs reported by investigators (≥15 percent) were increased aspartate aminotransferase, anemia, increased alanine aminotransferase, hypertension, constipation, decreased white blood cell count, neutropenia, decreased neutrophil count and hyperphosphatemia. Investigator-reported Grade 3 or higher treatment-related AEs (≥5 percent) were hypertension, neutropenia, anemia and decreased neutrophil count. Four percent of patients discontinued GAVRETO due to treatment-related AEs.
These data for GAVRETO are being reported in a proffered paper (Abstract Number: 1913O) at the
About RET-Altered Solid Tumors
RET activating fusions and mutations are key disease drivers in many cancer types, including NSCLC and multiple types of thyroid cancer. RET fusions are implicated in approximately 1 to 2 percent of patients with NSCLC and approximately 10 to 20 percent of patients with papillary thyroid cancer, while RET mutations are implicated in approximately 90 percent of patients with advanced MTC. In addition, oncogenic RET fusions are observed at low frequencies in colorectal, breast, pancreatic and other cancers, as well as in patients with treatment-resistant EGFR-mutant NSCLC.
About the ARROW Trial
The Phase 1/2 ARROW trial (ClinicalTrials.gov Identifier: NCT03037385) is designed to evaluate the safety, tolerability and efficacy of GAVRETO in adults with RET-altered cancers. The trial consists of two parts: a dose escalation portion, which is complete, and an expansion portion in patients treated at 400 mg QD. The study's objectives include assessing response, pharmacokinetics, pharmacodynamics and safety. The trial is enrolling patients at multiple sites in
Patients and physicians interested in the ARROW trial can contact the
About GAVRETO (pralsetinib)
GAVRETO (pralsetinib) is a once-daily oral targeted therapy approved by the FDA for the treatment of adults with metastatic RET fusion-positive NSCLC as detected by an FDA approved test. It is designed to selectively and potently target oncogenic RET alterations. In pre-clinical studies, GAVRETO inhibited RET at lower concentrations than other pharmacologically relevant kinases, including VEGFR2, FGFR2 and JAK2. For more information, visit GAVRETO.com.
GAVRETO is not approved for the treatment of any other indication in the
About
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 development and, if approved, commercialization of GAVRETO for the treatment of patients with RET-mutant MTC, RET fusion-positive thyroid cancer and other RET-altered cancers; the potential benefits of the
Trademarks
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Media Contact: Andrew Law, 617-844-8205, media@blueprintmedicines.com; Investor Relations Contact: Kristin Hodous, 617-714-6674, ir@blueprintmedicines.com