Phase 1 Study of JNJ-64619178, a Protein Arginine Methyltransferase 5 Inhibitor, in Advanced Solid Tumors.
Maria VieitoVictor MorenoAnna SpreaficoIrene BranaJudy S WangMeir PreisTatiana HernándezSofia GentaAaron Richard HansenBernard DogerVladimir GalvaoLaurie LenoxRegina J BrownAnna KalotaJaydeep MehtaFriederike PastoreBharvin PatelPankaj MistryJunchen GuJosh D LauringManish R PatelPublished in: Clinical cancer research : an official journal of the American Association for Cancer Research (2023)
JNJ-64619178 demonstrated manageable dose-dependent toxicity and preliminary evidence of antitumor activity in ACC and other tumor types. Plasma exposure was dose dependent, and target inhibition was maintained with intermittent and continuous dosing. Based on safety, clinical activity, PK, and PD findings, two provisional RP2Ds were selected: 1.5 mg intermittently and 1.0 mg once daily. Aside from ACC, clinical benefit was limited, and biomarkers to enrich for responsiveness to PRMT5 inhibition will be needed for further development.