Gene fusion is known as the oncogenic driver across multiple tumor types. The fusion proteins present opportunities for targeted drug development. The FDA has approved targeted drugs for ALK, ROS1, NTRK1/2/3 and FGFR2/3 gene fusion in solid tumors. RET is a receptor‑tyrosine kinase, and the RET rearrangements have been found to promote cell proliferation in cancer. ARROW trial is a phase I study, which evaluated the safety and antitumor activity of BLU-667, a new RET inhibitor, in advanced solid tumors with RET gene alteration. The results of 48 patients with RET fusion-positive NSCLC treated with 400 mg BLU-667 were presented at 2019 ASCO annual meeting. The overall response rate was 58% (95% CI: 43-72; one with complete response; 27 with partial responses). The efficacy of BLU-667 was regardless of RET fusion types, CNS involvement and treatment history. Other cancer types with partial response were also reported in the presentation, including one with metastatic pancreatic cancer, one with intrahepatic bile duct carcinoma and five with advanced papillary thyroid cancer. The safety profile showed BLU-667 was well tolerated. The results showed BLU-667 is tolerable and has antitumor activity in patients with RET fusion-positive tumor.
Gainor Justin F, et al. ASCO annual meeting 2019