agerafenib (RXDX-105)

P1/2 | " TAS0953/HM06 was more effective than RET multi-kinase inhibitors (cabozantinib, RXDX105, vandetanib), and equipotent to selpercatinib and pralsetinib, at inhibiting growth of patient-derived (8) and isogenic (2) cell lines harboring different RET fusions (IC50<0.1µM)... Our data show that TAS0953/HM06 is effective at inhibiting growth in vitro and in vivo of preclinical models driven by RET fusions. TAS0953/HM06 was more effective than selpercatinib at decreasing CNS disease and extending survival, at a dose that produced comparable suppression of tumor growth in extracranial disease models. TAS0953/HM06 represents a promising new therapeutic option for patients with RET fusions including those with brain metastasis and those resistant to first-generation selective RET inhibitors."

Moreover, cabozantinib was effective at reducing growth of a lung cancer PDX that was not responsive to RXDX-105...Notably, we identify MYC as a protein that is upregulated by RET expression and down-regulated by cabozantinib treatment, opening up potentially new therapeutic avenues for combinatorial targeting RET-fusion driven lung cancers. The novel RET fusion-dependent preclinical models described herein represent valuable tools for further refinement of current therapies and the evaluation of novel therapeutic strategies.

P1, N=3, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed

P1; N=143; Completed; Sponsor: Ignyta, Inc.; Active, not recruiting --> Completed; Trial completion date: Jun 2019 --> Feb 2019

P1, N=143, Completed, Ignyta, Inc. | Active, not recruiting --> Completed | Trial completion date: Jun 2019 --> Feb 2019