Dr. Gainor on Potential With BLU-667 in RET+ NSCLC

Justin F. Gainor, MD, director of Targeted Immunotherapy, Massachusetts General Hospital, assistant professor of medicine, Harvard Medical School, discusses clinical activity and tolerability of BLU-667 in patients with advanced RET fusion—positive non–small cell lung cancer (NSCLC).

BLU-667 is a highly potent and selective RET inhibitor targeting oncogenic RET alterations, including those that confer resistance to multikinase inhibitors. There are no currently FDA-approved RET inhibitors to date. Patients enrolled in the study had RET-altered advanced solid tumors and received 30 mg to 600 mg of oral BLU-667 daily. The first part of the ARROW study determined 400 mg of BLU-667 daily as the recommended dose.

The second part of the ARROW study sought to identify the overall response rate (ORR) and safety of BLU-667. The study enrolled 120 patients, 91 of them having completed prior platinum-based chemotherapy. Of all patients, 84% had received prior therapy; 77% had chemotherapy, 39% had a PD-1/PD-L1 inhibitor, 34% had the combination of chemotherapy and a checkpoint inhibitor, and 18% received a multikinase inhibitor.

Treatment-related toxicity was generally low-grade, with some adverse events including constipation (17%; grade ≥3, 2%), neutropenia (26; grade ≥3, 13%), aminotransferase increase (20%; grade ≥3, 2%), fatigue (13%; grade ≥3, 3%), and hypertension (13%; grade ≥3, 10%).

The preliminary efficacy of BLU-667 was evaluated in 48 patients. Results showed that the ORR was 58% and the disease control rate (DCR) was 96%. Of those 48 patients, 35 received prior platinum-based chemotherapy. In that subgroup, the ORR was 60% and the DCR was 100%.

These data support the expansion of the ARROW trial in treatment-naïve NSCLC patients and continued enrollment of other RET-altered solid tumor groups.