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.

Up to 40% of patients have the highly aggressive androgen receptor variant 7 (AR-V7), which is resistant to ARSi therapy.

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 Demonstrated in Zytiga®-Resistant Patients Treated with Onvansertib
  • Overall, 63% (12 of 19) of evaluable patients achieved partial response (PR) or stable disease (SD) following 12 weeks of treatment with onvansertib + abiraterone
  • Response to treatment was evaluated based on PSA values (primary endpoint) and radiographic scans

Evaluation of PSA and Radiographic Response At 12-Weeks

Treatment Duration

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

CTC count, reported as favorable or unfavorable (<5 versus ≥5 CTC/7.5mL of blood, respectively) is a prognostic factor for survival in CRPC and the conversion from unfavorable to favorable is associated with improved survival7

  • At baseline, 25 (78%) patients had unfavorable CTC count with median of 19 CTC/7.5mL
  • 10 of the unfavorable patients were re-analyzed after 12 weeks of treatment
    • 5 (50%) patients had a of 80% CTC decrease, including 2 AR-V7+ patients (01-024 and 01-025)
    • 4 (40%) patients converted from unfavorable to favorable CTC level (<5 CTC/7.5mL)
    • 3 (30%) patients had no detectable CTC
    • Median time on treatment for patients with decrease CTC (n=5) is 7 months to-date, with 4 patients remaining on treatment
  • Conversely, median time on treatment for patients with increase CTC (n=5) was 5 months, and none of these patients remain on treatment

% Change in CTC at 12-Weeks vs Baseline in Patients with Unfavorable CTC Level at Baseline