Blueprint Medicines announces updated data from Phase 1 ARROW clinical trial
Blueprint Medicines announced the presentation of updated data from the ongoing Phase 1 ARROW clinical trial of BLU-667, an investigational precision therapy targeting RET alterations, including resistance mutations. The new results showed that BLU-667 was highly active and well-tolerated in patients with advanced RET-altered medullary thyroid cancer and papillary thyroid cancer, with increased activity observed with higher dose levels and longer treatment durations. The reported data showed 90% of evaluable patients with MTC and PTC had radiographic tumor reductions, regardless of RET alteration type or prior multi-kinase inhibitor therapy. In addition, the response rate was 62% in patients with MTC treated once daily with BLU-667 at doses of 300 to 400 mg for at least 24 weeks. In the MTC and PTC populations, all responders across dose levels and all patients treated at 400 mg QD remain on study. Safety results were consistent with prior data, and the majority of adverse events were Grade 1. These results were as of a data cutoff date of September 14, 2018 and were reported in an oral presentation at The 88th Annual Meeting of the American Thyroid Association. Based on the encouraging data reported to date, Blueprint Medicines has expanded enrollment targets for the ARROW trial to further evaluate the safety and efficacy of BLU-667 in a broader patient population and, ultimately, to support potential registration. The data presented included all patients enrolled in the Phase 1 ARROW clinical trial as of May 9, 2018 and included follow-up on these patients through the data cutoff date of September 14, 2018. Of the 69 patients who had been treated with BLU-667 in the dose escalation and expansion portions of the trial, 42 had RET-altered thyroid cancer, including 37 with MTC and five with PTC. In the dose escalation portion, patients were treated at dose levels ranging from 30 mg to 600 mg QD or up to 300 mg twice daily. In the expansion portion, patients were treated at the recommended phase 2 dose of 400 mg QD. As of the data cutoff date, 35 patients with MTC and four patients with PTC were evaluable for response assessment by Response Evaluation Criteria in Solid Tumors version 1.1. Overall, 90% of MTC and PTC patients with measurable target lesions had radiographic tumor reductions. In patients with MTC, response assessments showed increased clinical activity with higher dose levels and longer treatment durations. Across all evaluable MTC patients, the overall response rate was 49%, including one patient with a confirmed complete response and 16 patients with a partial response. In patients with MTC treated with 300 to 400 mg QD for at least 24 weeks, the response rate was 62%, including one patient with a confirmed CR and seven patients with a confirmed PR. In patients with PTC, two of four evaluable patients had a confirmed PR, and all evaluable patients with PTC had radiographic tumor shrinkage. The data also showed encouraging evidence of durable activity. All patients with MTC and PTC who responded to BLU-667 remain on treatment as of the data cutoff date. In addition, all patients treated at 400 mg QD are continuing on therapy. Patients with the longest treatment durations remain on therapy for more than 15 months. Anti-tumor activity was observed regardless of prior MKI therapy or RET alteration. The reported data showed that across 69 patients, BLU-667 was well-tolerated as of the data cutoff date. Most AEs were Grade 1, and only two patients discontinued therapy due to a treatment-related AE - Grade 3 increased alanine aminotransferase in a patient with liver metastases and Grade 2 pneumonitis.