Benzinga | Sep 20, 2020 08:32AM EDT

Blueprint Medicines Presents ARROW Trial Data at ESMO 2020 Demonstrating Durable Clinical Benefits of GAVRETO in Patients with Advanced RET-Mutant Medullary Thyroid Cancer

Blueprint Medicines Corporation (NASDAQ:BPMC) today announced results from the ongoing ARROW clinical trial showing durable responses and a well-tolerated safety profile for GAVRETO(tm) (pralsetinib) in patients with advanced RET-mutant medullary thyroid cancer (MTC). In these registrational data, GAVRETO demonstrated consistent clinical activity in patients across lines of therapy and regardless of RET mutation genotypes, including a high response rate in patients with gatekeeper mutations resistant to multi-kinase inhibitors. The results are being presented today in a proffered paper session during the European Society for Medical Oncology (ESMO) Virtual Congress 2020.

"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 Mimi Hu, M.D., professor in the Department of Endocrine Neoplasia and Hormonal Disorders at The University of Texas MD Anderson Cancer Center. "The reported data highlight the robust clinical activity and safety of GAVRETO, with most patients remaining on treatment for prolonged periods of time. These results are a promising advancement for RET-mutant medullary thyroid cancer across both systemic treatment-nave and previously treated patients."

"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 Andy Boral, M.D., Ph.D., Chief Medical Officer at Blueprint Medicines. "Across first-line and previously treated settings, GAVRETO has shown durable clinical benefits and a well-tolerated safety profile that has remained consistent over time. With the recent FDA approval of GAVRETO in patients with RET fusion-positive metastatic non-small cell lung cancer, these data further support our efforts to bring this once-daily treatment to patients across multiple RET-driven tumor types."

As previously announced, the U.S. Food and Drug Administration (FDA) has accepted a new drug application (NDA) for GAVRETO for the treatment of patients with advanced or metastatic RET-mutant MTC and RET fusion-positive thyroid cancer. This NDA was accepted for priority review under the FDA's Real-Time Oncology Review (RTOR) pilot program, which aims to explore a more efficient review process to ensure safe and effective treatments are available to patients as early as possible.

In addition, Blueprint Medicines today announced that the National Comprehensive Cancer Network has updated its Clinical Practice Guidelines in Oncology (NCCN Guidelines(r)) for Non-Small Cell Lung Cancer (NSCLC) to include GAVRETO as a preferred treatment option (category 2A) for patients with RET fusion-positive NSCLC as a first-line or subsequent therapy. This rating indicates that there is uniform NCCN consensus that the intervention is appropriate. The NCCN Guidelines are the recognized clinical standard for cancer care by U.S. healthcare providers and payers, and are maintained by a committee of expert physicians from leading U.S. cancer centers.

GAVRETO is being jointly commercialized by Genentech, a wholly owned member of the Roche Group, and Blueprint Medicines in the U.S. and will be commercialized by Roche outside of the U.S., excluding Greater China (Mainland China, Hong Kong, Macau and Taiwan).

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 nave 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 February 13, 2020.

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-nave 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-nave 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 ESMO Virtual Congress 2020. A copy of the data presentation is available in the "SciencePublications and Presentations" section of Blueprint Medicines' website at www.BlueprintMedicines.com.