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Onvansertib shows promise in abiraterone-resistant mCRPC


Adding the PLK1 inhibitor to abiraterone acetate and prednisone led to disease control in patients showing initial signs of progression on abiraterone.

Adding onvansertib to abiraterone acetate (Zytiga) and prednisone showed promising clinical activity in patients with metastatic castration-resistant prostate cancer (mCRPC) with initial resistance to abiraterone, according to phase 2 findings shared during the 27th Annual Prostate Cancer Foundation (PCF) Scientific Retreat.1,2

Initial study results for 26 evaluable patients showed that 8 (31%) reached the primary study end point of disease control (no PSA progression) following 12 weeks of treatment. After the same length of treatment, another 14 patients (54%) achieved stable disease (SD), with 8 of these patients having SD for at least 7 months. Also of note, among 8 patients whose tumors had androgen receptor alterations linked to abiraterone resistance, 3 reached disease control and 4 achieved SD at 12 weeks.

"There is a pressing unmet need for therapies that can address resistance to abiraterone and other androgen receptor signaling inhibitors (ARSi) in mCRPC," principal investigator David Einstein, MD, attending physician at Beth Israel Deaconess Medical Center stated in a press release.1 "Data presented at the PCF retreat demonstrate the potential of onvansertib to address this need, as we are seeing clinically meaningful rates of disease control, some quite durable, in patients with known mechanisms of ARSi resistance."

Onvansertib is an oral PLK1 inhibitor. Research has shown that PLK1 is overexpressed in prostate tumors and is associated with higher grade prostate cancers.

The open-label, phase 2 study is exploring onvansertib combined with abiraterone/prednisone in patients with mCRPC receiving abiraterone/prednisone and showing early signs of progressive disease. The study defined initial progressive disease as tests showing 2 rising PSA values separated by ≥1 week of the patients having minimal or no symptoms. As of September 3, 2020, 39 patients had been treated across the study’s 3 dosing schedules, which comprised onvansertib at 24 mg/m2, 18 mg/m2 or 12 mg/m2.

The efficacy results shared during the retreat included 17 patients receiving the 24 mg/m2 schedule and 9 patients receiving the 18 mg/m2 schedule. In the press release, it was separately noted that 2 of the 3 efficacy-evaluable patients receiving the 12 mg/m2 schedule had also achieved disease control at 12 weeks.1

Across all 39 treated patients, the median age was 72 years (range, 54-87), 87% of patients were White, and 87% had an ECOG performance status of 0. The median number of years since diagnosis was 5 (range, 1-18), the median baseline PSA was 12.5 ng/mL (range, 0.6-224), 62% were grade groups 4 and 5, and 33% had de novo metastatic disease. Visceral metastasis was present in 33% of cases, with bone metastasis occurring in 85%.

Safety data across all 39 treated patients showed that the combination of onvansertib and abiraterone was tolerable across the 3 dosing schedules of the PLK1 inhibitor. Grade 3 adverse events (AEs) occurring across the 3 dosing schedules were anemia (n = 1), neutropenia (n = 7), hypophosphatemia (n = 4), white blood cell (WBC) decrease (n = 3), hypokalemia (n = 1). Grade 4 AEs across all doses included thrombocytopenia (n = 1), neutropenia (n = 3), and WBC decrease (n = 2).


1. Cardiff Oncology Presents Positive Efficacy and Biomarker Data from mCRPC Trial Demonstrating Ability of Onvansertib to Overcome Zytiga® Resistance. Cardiff Oncology. https://prn.to/3dHykvg. Published online October 20, 2020. Accessed October 20, 2020.

2. Einstein DJ, Choudhury A, Saylor P, et al.A phase 2 study of the polo-like kinase 1 (PLK1) inhibitor, onvansertib, in combination with abiraterone in patients with abiraterone-resistant metastatic castration-resistant prostate cancer (mCRPC). Presented during the 27th Annual Prostate Cancer Foundation Scientific Retreat. October 20-23, 2020.

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