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Drilon A, Fu S, Patel MR, Fakih M, Wang D, Olszanski AJ, Morgensztern D, Liu SV, Cho BC, Bazhenova L, Rodriguez CP, Doebele RC, Wozniak A, Reckamp KL, Seery T, Nikolinakos P, Hu Z, Oliver JW, Trone D, McArthur K, Patel R, Multani PS, Ahn MJ
A Phase I/Ib Trial of the VEGFR-Sparing Multikinase RET Inhibitor RXDX-105
Cancer Discov (2019) 9:384-395.
RET fusions are oncogenic drivers of various tumors, including non-small cell lung cancers (NSCLCs). The safety and antitumor activity of the multikinase RET inhibitor RXDX-105 were explored in a phase I/Ib trial. A recommended phase 2 dose of 275 mg fed daily was identified. The most common treatment-related adverse events were fatigue (25%), diarrhea (24%), hypophosphatemia (18%), maculopapular rash (18%), and non-maculopapular rash (17%). In the phase 1b cohort of RET inhibitor-naive patients with RET fusion-positive NSCLCs, the objective response rate (ORR) was 19% (95% CI 8%-38%, n=6/31). Interestingly, the ORR varied significantly by the gene fusion partner (p<0.001, Fisher's exact test): 0% (95% CI 0% - 17%, n=0/20) with KIF5B (the most common upstream partner for RET fusion-positive NSCLC), and 67% (95% CI 30% - 93%, n=6/9) with non-KIF5B partners. The median duration of response in all RET fusion-positive NSCLCs was not reached (range 5 to 18+ months).
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Publication Date: 2019-03-01.
PMCID: PMC6397691
Last updated on Saturday, August 22, 2020