(UroToday.com) Rucaparib is an inhibitor of poly (ADP-ribose) polymerase – PARP – that is approved for the treatment of BRCA1 and BRCA2 mutated metastatic castration-resistant prostate cancer (mCRPC) based on the recently published TRITON2 study. Enzalutamide is an androgen receptor antagonist that is approved for the treatment of mCRPC as well as metastatic castration sensitive prostate cancer (mHSPC). Preclinical studies have demonstrated potential synthetic lethality between androgen receptor signaling inhibition and PARP inhibition, which led to the investigation of these two drugs in combination. As enzalutamide strongly induces CYP3A4, which may contribute to the processing of rucaparib into its oxidative metabolite, the phase 1 RAMP study (NCT04179396) was designed to investigate potential drug-drug interactions and pharmacokinetics in genomically unselected patients as well as safety with the combination of enzalutamide and rucaparib. In this abstract, Arpit Rao presented pharmacokinetic, safety, and preliminary efficacy data for this drug combination in eight patients.

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