Turning the Tide

on Zytiga®-Resistant Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Adding Onvansertib to Daily Zytiga is Increasing the Duration of Response to Treatment and Progression-Free Survival

Zytiga®-Resistant Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Resistance develops to standard-of-care androgen receptor signaling inhibitors (ARSi) therapy, Zytiga® and Xtandi®, within 9-15 months.

ARSi’s offer a median overall survival (mOS) benefit of only ~4 months

Onvansertib + Zytiga® (abiraterone) Demonstrates Synergy in mCRPC Model (C4-2)

Onvansertib + Zytiga® (abiraterone) Significantly Increases Mitotic Arrest

Why onvansertib is a promising option for mCPRC: Overcoming resistance to Zytiga

Onvansertib in combination with Zytiga (abiraterone) demonstrates synergy in mCRPC and significantly increases the arrest of tumor cell division.

Why onvansertib is a promising option for mCRPC with the AR-V7 mutation:

PLK1 inhibitor in combination with Zytiga (abiraterone) blocks tumor growth and PSA increase in AR-V7 positive CRPC preclinical model.

The combination of Zytiga (abiraterone) and onvansertib reduces AR and AR-V7 protein expression in CRPC cell lines.

PLK1 Inhibition Enhances the Efficacy of Androgen Signaling Blockade in Castration-Resistant Prostate Cancer

Onvansertib in Combination with FOLFIRI/Avastin® is Demonstrating Safety and Efficacy in KRAS-Mutated Metastatic Colorectal Cancer

Phase 2 multi-center open-label clinical trial NCT03414034

“This data shows that adding onvansertib to abiraterone in metastatic castration-resistant prostate cancer patients with an early resistance to abiraterone validates pre-clinical studies and shows potential as a new therapeutic option.”

Dr. David Einstein, principal investigator at the Beth Israel Deaconess Medical Center

Efficacy in patients with AR alterations:

Nineteen (53%) patients had at least 1 AR alteration associated with abiraterone-resistance (AR-V7 expression, AR mutation T878A and/or amplification of AR)1:

  • 5 (26%) patients had disease control at 12 weeks

  • 8 (42%) patients had radiographic stable disease at 12 weeks

Onvansertib-Induced CTC Decrease is Associated with Progression-Free Survival

Circulating tumor cell (CTC) count, reported as favorable or unfavorable (<5 versus ≥5 CTC/7.5mL of blood, respectively) is a prognostic factor for survival in CRPC – conversion from unfavorable to favorable is associated with improved survival

10 patients with unfavorable CTC at baseline were re-analyzed after 12 weeks of treatment:

  • 5 (50%) patients had an ≥80% CTC decrease, including 2 AR-V7+ patients (01-024 and 01-025)
  • 4 (40%) patients converted from unfavorable to favorable CTC level, including 3 patients with no detectable CTC
  • Median time on treatment was 9.2 months for patients with CTC decrease (n=5) vs 4.9 months for patients with CTC increase (n=5)