Trovagene (TROV) Highlights Phase 2 Data Demonstrating the Ability of Onvansertib to Overcome Zytiga-Resistance and Provide Clinical Benefit for mCRPC Patients

Trovagene, Inc. (NASDAQ: TROV) today announced positive data from its ongoing Phase 2 trial of onvansertib in combination with Zytiga® (abiraterone – Johnson & Johnson)/prednisone, all administered orally, for the treatment of patients with Zytiga®-resistant metastatic castration-resistant prostate cancer (mCRPC).

The clinical data, featured in a poster presentation today at the American Society for Clinical Oncology (ASCO) 2020 Genitourinary Cancers Symposium in San Francisco, further demonstrates the efficacy of onvansertib in patients who develop resistance to first-line treatment with Zytiga®. Onvansertib addresses Zytiga® resistance across known androgen receptor (AR) resistance mechanisms. In patients with AR alterations, 86% had decreases in PSA levels with the addition of onvansertib to daily Zytiga®.

"Metastatic castration-resistant prostate cancer is the second leading cause of cancer-related death among men in the United States, and unfortunately many patients are in desperate need of new treatment options," said study principal investigator Dr. David Einstein, Genitourinary Oncology Program, Beth Israel Deaconess Medical Center. "These data show 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."

"We are very encouraged by the significant decreases in circulating tumor cells (CTCs) with the addition of onvansertib, given that these changes in CTCs are an accepted surrogate prognostic factor for efficacy and survival," said Dr. Mark Erlander, Chief Scientific Officer at Trovagene. "In addition, observing efficacy in patients that have tumors exhibiting known mechanisms of resistance to ARS inhibitor, Zytiga®, suggests that onvansertib's activity could extend to overcoming resistance to other ARS inhibitors such as Xtandi® and Erleada®."

Key Presentation Highlights:

Efficacy

• Overall, across both arms (A and B), a 63% (12 of 19) response (Stable Disease – SD and Partial Response – PR) was observed in patients evaluable for efficacy (completed 12 weeks of treatment with onvansertib + Zytiga® (abiraterone)/prednisone); 6 patients have been on treatment for ≥7 months
  • Arm B (onvansertib dosed daily on days 1-5 in a 14-day cycle)
    • 80% (4 of 5) patients had SD at 12 weeks, with 3 patients achieving the efficacy endpoint (PSA stabilization) and 3 patients remain on treatment
    • 60% (3 of 5) patients have or had progression-free survival of >7 months
  • Arm A (onvansertib dosed daily on days 1-5 in a 21-day cycle)
    • 57% (8 of 14) patients had SD or PR at 12 weeks, with 5 patients achieving the efficacy endpoint (PSA stabilization) and 4 patients remain on treatment
    • 21% (3 of 14) patients have or had progression-free survival; 2 patients remain on treatment for >1 year
• Onvansertib-induced circulating tumor cell (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 survival
  • 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 ≥80% CTC decrease, including 2 AR-V7+ patients
    • 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=4) 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
• Efficacy observed in patients with Zytiga®-resistant androgen receptor (AR) alterations
  • AR mechanisms of resistance to abiraterone include the expression of the constitutively active AR splice variant AR-V7 and the AR gain-of function point mutation T878A
  • Among the 19 patients who completed the 12-week treatment (Arm A + B):
    • 5 patients were AR-V7+ at baseline
    • 2 patients had AR T878A mutations at baseline
  • Onvansertib showed efficacy in patients with AR alterations (N=7):
    • 6 (86%) patients had a decrease in PSA levels with the addition of onvansertib
    • 4 (57%) patients had SD or PR at 12 weeks with 3 (43%) patients achieving the primary efficacy endpoint
    • 3 patients have or had progression-free survival of >7 months, 2 patients remain on treatment

Safety

• Safety lead-in cohort was completed in Arm A at 24 mg/m2 and is ongoing in Arm B at 18 mg/m2
• Most frequent G3/G4 AEs were expected, on-target, reversible hematological (anemia, neutropenia, thrombocytopenia and leukopenia), associated with the mechanism of action of onvansertib
  • Hematological AEs were reversible and effectively managed by dose delay, dose reduction and/or growth factor support
• Grade 3 hypophosphatemia was reported in 3 patients, next cycle treatment was delayed for 2 patients to allow recover

Conclusions

• Overall, across both arms (A and B), a 63% (12 of 19) response (SD + PR) was observed in patients evaluable for efficacy (completed 12 weeks of treatment); 6 patients have been on treatment for ≥7 months
• Onvansertib induced profound CTC decreases in patients with unfavorable CTC count (>80% decrease in 5 of 10 patients tested); CTC decrease was associated with prolonged response to treatment and progression-free survival
• 6 of 7 patients with AR alterations (AR-V7+ or AR T878A) had an immediate decrease in PSA following onvansertib treatment; efficacy (SD+PR) was achieved in 57% (4 of 7) patients
• In both arms (A and B) onvansertib in combination with abiraterone was safe and well-tolerated
• A more continuous dosing schedule (Arm C – onvansertib 12 mg/m2 on days 1-14 of a 21-day cycle) is planned to evaluate safety and efficacy
• Adding onvansertib to abiraterone in mCRPC patients resistant to abiraterone (rising PSA) validates pre-clinical studies and shows promise as a new therapeutic option

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