On November 14, 2019 Trovagene, Inc. (Nasdaq: TROV), a clinical-stage, Precision Cancer Medicine oncology therapeutics company developing drugs that target cell division (mitosis), for the treatment of various cancers including prostate, colorectal and leukemia, reported new positive data from its Phase 2 trial evaluating onvansertib in combination with Zytiga (abiraterone acetate – Johnson & Johnson)/prednisone in patients with metastatic Castration-Resistant Prostate Cancer (mCRPC) (Press release, Trovagene, NOV 14, 2019, View Source [SID1234551282]). The data are being presented today at the European Multidisciplinary Congress on Urological Cancers (EMUC) in Vienna, Austria.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"The new data shared today builds upon the encouraging clinical response seen to date when onvansertib is added to treatment in patients who have developed resistance to androgen receptor signaling inhibitor (ARSi), Zytiga," said Dr. Mark Erlander, Chief Scientific Officer of Trovagene. "Of particular significance are the positive results we are observing in patients who harbor the highly aggressive, resistant variant of the androgen receptor (AR-V7). These patients are resistant to ARS inhibitors including Zytiga and Xtandi (enzalutamide – Pfizer) and their therapeutic options are not only limited, but often ineffective. We believe the addition of onvansertib has the potential to deliver transformative benefit to patients with mCRPC by extending the duration of response to treatment with ARS inhibitors."
Data Summary
The newly reported data include efficacy and safety assessments as of the October 28, 2019 data cut-off date for 15 patients that completed 3 months of treatment and were eligible for evaluation of the primary efficacy endpoint of disease control. Response to treatment was evaluated based on a decrease or stabilization in prostate specific antigen (PSA) values (primary endpoint) and confirmed by radiographic scans.
Efficacy
Overall, across both arms (A and B), a 60% response (SD + PR) was observed in patients who were evaluable for efficacy (completed 3 months of treatment); 72% of patients had a decrease in PSA following one cycle of treatment with onvansertib; 6 patients remain on treatment for ≥4 months.
Trovagene Inc. | 11055 Flintkote Avenue | San Diego | CA 92121 | Tel.: USA [+1] 888-391-7992
All 5 patients who tested positive for the highly-aggressive, resistant AR-V7 variant had decreases in PSA following one cycle of treatment with onvansertib; the primary efficacy endpoint (SD + PR) was achieved in 3 out of 4 evaluable patients (completing 12 weeks of treatment).
Safety
In both arms (A and B) onvansertib in combination with abiraterone was safe and well-tolerated. The most frequent adverse events (AEs) were expected, on-target (based on mechanism of action of onvansertib) hematologic (anemia, neutropenia, thrombocytopenia and white blood cell (WBC) decrease). All hematologic AEs were easily and effectively managed and resolved by delaying or reducing the dose and/or adding growth factor support. No unexpected or off-target AEs have been reported to-date.
About the Phase 2 Trial of Onvansertib in mCRPC
The trial is a Phase 2 open-label multi-center study of onvansertib in combination with Zytiga (abiraterone acetate)/prednisone in patients with mCRPC, showing signs of disease progression and resistance to Zytiga demonstrated by two rising PSA values separated by at least one week, while on Zytiga(NCT03414034). The primary efficacy endpoint is the proportion of patients achieving disease control after 12 weeks of study treatment, as defined by lack of prostate specific antigen (PSA) progression. The trial is being conducted by Beth Israel Deaconess Medical Center (BIDMC), Dana-Farber Cancer Institute (Dana-Farber), and Massachusetts General Hospital Cancer Center (MGH). David Einstein, MD, Genitourinary Oncology Program at BIDMC, is the principal investigator for the trial.
About Onvansertib
Onvansertib is a first-in-class, third-generation, oral and highly-selective adenosine triphosphate (ATP) competitive inhibitor of the serine/threonine polo-like-kinase 1 (PLK1) enzyme, which is over-expressed in multiple cancers including leukemias, lymphomas and solid tumors. Onvansertib targets the PLK1 isoform only (not PLK2 or PLK3), is orally administered and has a 24-hour half-life with only mild-to-moderate side effects reported. Trovagene believes that targeting only PLK1 and having a favorable safety and tolerability profile, along with an improved dose/scheduling regimen will significantly improve on the outcome observed in previous studies with a former panPLK inhibitor in AML.
Onvansertib has demonstrated synergy in preclinical studies with numerous chemotherapies and targeted therapeutics used to treat leukemias, lymphomas and solid tumor cancers, including irinotecan, FLT3 and HDAC inhibitors, taxanes and cytotoxins. Trovagene believes the combination of onvansertib with other compounds has the potential to improve clinical efficacy in acute myeloid leukemia (AML), metastatic castration-resistant prostate cancer (mCRPC), non-Hodgkin lymphoma (NHL), colorectal cancer and triple-negative breast cancer (TNBC), as well as other types of cancer.
Trovagene has three ongoing clinical trials of onvansertib: A Phase 2 trial of onvansertib in combination with Zytiga (abiraterone acetate)/prednisone in patients with mCRPC who are showing signs of early progressive disease (rise in PSA but minimally symptomatic or
asymptomatic) while currently receiving Zytiga (NCT03414034); a Phase 1b/2 Study of onvansertib in combination with FOLFIRI and Avastin for second-line treatment in patients with mCRC with a KRAS mutation (NCT03829410); and a Phase 1b/2 clinical trial of onvansertib in combination with low-dose cytarabine or decitabine in patients with relapsed or refractory AML (NCT03303339). Onvansertib has been granted orphan drug designation by the FDA in the U.S. and by the EC in the European Union for the treatment of patients with AML.
Trovagene licensed onvansertib (also known as NMS-1286937 and PCM-075) from Nerviano Medical Sciences (NMS), the largest oncology-focused research and development company in Italy, and a leader in protein kinase drug development. NMS has an excellent track record of licensing innovative drugs to pharma/biotech companies, including Array (recently acquired by Pfizer), Ignyta (acquired by Roche) and Genentech.