Add-on Onvansertib Overcomes Resistance to Zytiga in mCRPC, Early Data Show

Add-on Onvansertib Overcomes Resistance to Zytiga in mCRPC, Early Data Show
Adding the investigational oral therapy onvansertib to a regimen of Zytiga (abiraterone acetate) and prednisone overcomes resistance to Zytiga in men with metastatic castration-resistant prostate cancer (mCRPC), according to early results of a Phase 2 clinical trial. The study (NCT03414034) is testing whether a once-daily dose of Trovagene’s onvansertib is beneficial in adults with mCRPC who experienced cancer progression on Janssen’s Zytiga and prednisone. Patient enrollment is ongoing, for a planned total of 64 participants. (More information about contacts and the three U.S. locations is available here.) Patients with mCRPC typically develop resistance to standard-of-care medications such as Zytiga — an androgen-receptor signaling (ARS) inhibitor — within nine to 15 months of beginning treatment. In some cases, resistance develops when cells produce a variant of the androgen receptor, called AR-V7, that lacks the domain targeted by current androgen receptor inhibitors. In other cases, cancer cells overproduce the androgen receptor. In the ongoing Phase 2 trial, patients are receiving a blood test to determine if they have the AR-V7 variant. So far, the four patients who tested positive for AR-V7 showed an immediate decrease in serum PSA levels, indicating a positive response to treatment. Two of these patients also achieved disease control, the study’s primary efficacy goal. Interestingly, one of the AR-V7-positive patients had experienced a greater than fivefold increase in his PSA level within two months while on Zytiga. "We have discovered that adding onvansertib to daily ARS inhibitor therapy changes the trajectory of resistance in patients harboring AR-V7," Mark Erlander, PhD, Trovagene’s chief scientific officer, said in a press re
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