BLU-667 active against RET fusion-positive advanced NSCLC
medwireNews: Phase I data indicate that the selective RET inhibitor BLU-667 elicits durable responses and is well tolerated by individuals with advanced non-small-cell lung cancer (NSCLC) harboring a RET fusion.
The presenting author – Justin Gainor, from Massachusetts General Hospital in Boston, USA – told delegates at the 2019 ASCO Annual Meeting in Chicago, Illinois, USA, that “responses were observed regardless of treatment history, RET fusion partner, or CNS [central nervous system] involvement.”
BLU-667 has been granted breakthrough therapy status by the US FDA for RET fusion-positive NSCLC that has progressed on platinum-based chemotherapy, he added.
Gainor explained that the second part of the phase I ARROW trial includes seven dose expansion cohorts of patients with solid tumors receiving BLU-667 at a starting dose of 400 mg/day, with the two NSCLC cohorts the focus of his presentation.
Among the 120 participants (91 with prior platinum-based treatment) positive for a RET fusion, but with no other driver mutation, treatment-related toxicity was “generally low-grade and reversible,” said the presenter.
The most common treatment-related adverse event of at least grade 3 was neutropenia, occurring at a rate of 13%, followed by hypertension, at 10%. And 7% of patients discontinued the study drug owing to treatment-related toxicity.
The overall response rate (ORR) for the 48 evaluable patients was 58%, with an ORR of 60% for the 35 participants who had previously received platinum-based chemotherapy. The respective disease control rates were 96% and 100%.
Seven of the patients were treatment-naïve and the ORR in this subgroup was 71%.
Of note, 82% of the responders were continuing treatment with BLU-667 at the time of data cutoff, and the median duration of response is unreached.
Responses were observed in patients who had and had not received prior treatment with PD-1 or PD-L1 inhibitors, and among those with and without CNS involvement, including in 78% of the nine patients with measurable intracranial metastases. BLU-667 also appeared to be efficacious irrespective of the RET fusion partner, be it CCDC6, KIF5B, or an unknown or other gene.
Gainor therefore concluded that these “data support expansion of [the] ARROW trial in treatment-naïve NSCLC patients and continued enrollment of other RET-altered solid tumor groups.”
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