Blueprint reports promising phase 1 data in RET-altered tumors: AACR

The biotech is waiting on confirmation of partial response in a handful of patients, but if verified, about 50% of NSCLC patients and 40% of medullary thyroid cancer patients experienced enough tumor shrinkage to have a partial response. (PDPics)

Blueprint Medicines presented proof-of-concept data from a phase 1 trial of its BLU-667, which targets RET mutations and fusions, a key driver in some cancers. The trial tested the drug against patients with lung or thyroid cancer and the data showed that tumors shrank in 84% of evaluable patients.

BLU-667, an RET inhibitor, is among four kinase inhibitors that the Cambridge, Massachusetts, biotech has in phase 1. The data comes from the dose escalation part of the study, which involved 53 patients, of whom 40 were evaluable. The patients had advanced disease and many had received prior treatments, including immunotherapy, multi-kinase therapy and chemotherapy, and received a daily dose of BLU-667 ranging from 30 mg to 600 mg.

Of the 14 patients with non-small cell lung cancer (NSCLC), 13 had evaluable lesions, with 11 showing tumor shrinkage and five showing a partial response, the company said. The treatment posted a similar rate of tumor reduction in the 24 evaluable patients with medullary thyroid cancer (83%).

One patient had a complete response, while five had a partial response. The company is still waiting on confirmation of partial response for two NSCLC patients and four MTC patients, which would boost the response rate for both patient groups.

“The BLU-667 data show robust antitumor activity across multiple tumor and RET alteration types with a favorable tolerability profile, which is a highly encouraging outcome for the dose escalation portion of this Phase 1 clinical trial. With this solid foundation, we are rapidly advancing the global expansion portion of the ongoing ARROW trial with the goal of further defining the safety and efficacy of BLU-667 in patients with RET-altered cancers.”

It’s still early days, of course, said CEO Jeff Albers, and the company will be moving forward with the optimized dose. It will ramp up enrollment of the trial to investigate the drug’s activity in different tumor types—RET mutations are found in 60% of patients with MTC and 1 to 2% of patients with NSCLC, and are also implicated in breast and colon cancers, the company said.

“It’s important to remember that although RET is relatively rare in terms of cancer-causing mutations, it does affect 10,000 lung cancer patients worldwide every year,” Boral said. “These patients are not yet benefiting from targeted cancer therapies that other patient populations are benefiting from.”

Blueprint isn’t the only player targeting RET—Loxo Oncology is also working on an RET inhibitor, which is currently in phase 1. It inked a companion diagnostics deal with Illumina last week, under which the diagnostics maker will use its next-generation sequencing technology TruSight Tumor 170 as the basis for a test that identifies the NTRK fusions and RET gene alterations targeted by Loxo’s drugs.