On April 1, 2020 Trovagene, Inc. (Nasdaq: TROV), a clinical-stage, oncology therapeutics company developing onvansertib for the treatment of various cancers including colorectal, prostate and leukemia, reported that its Phase 1b/2 clinical trial of onvansertib in combination with standard-of-care FOLFIRI/Avastin (bevacizumab) for second-line treatment of patients with KRAS-mutated mCRC, will be featured in a presentation at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting to be held from May 29 – June 2 (Press release, Trovagene, APR 1, 2020, View Source [SID1234556073]).
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There is a significant, unmet medical need to develop a safe and effective second-line treatment option for patients with KRAS-mutated mCRC. Currently available treatments have limited efficacy with only a 4% response rate and a median of 5.5 months progression-free survival (PFS). Other compounds currently in clinical development that target KRAS-mutated cancers have shown minimal activity in mCRC.
Data presented at the ASCO (Free ASCO Whitepaper)-GI meeting in late January showed the effectiveness of onvansertib against all prevalent KRAS mutations associated with mCRC by quantitative decreases in the plasma KRAS mutation levels in treated patients within the first cycle of treatment. Subsequent radiographic scans performed at 8 and 16 weeks confirmed efficacy by measurable shrinkage of tumors in all patients.
"We are excited to have our abstract accepted for presentation at the prestigious ASCO (Free ASCO Whitepaper) annual meeting," said Dr. Thomas Adams, Chief Executive Officer and Chairman of Trovagene. "Despite more than 30 years of intensive efforts, anti-KRAS therapies have remained elusive, and currently there are no drugs effectively targeting a broad spectrum of KRAS mutations. We believe onvansertib has the potential to provide a substantially improved treatment option for second-line treatment of patients with KRAS-mutated mCRC."
About the Phase 1b/2 Trial of Onvansertib in Metastatic KRAS-mutated Colorectal Cancer
The trial, A Phase 1b/2 Study of Onvansertib (PCM-075) in Combination with FOLFIRI and Bevacizumab for Second‑Line Treatment of Metastatic Colorectal Cancer in Patients with a KRAS Mutation (NCT03829410), will evaluate the safety and efficacy of onvansertib in combination with standard-of-care FOLFIRI and Avastin (bevacizumab). Up to 44 patients, with a confirmed KRAS mutation, metastatic and unresectable disease, who have failed or are intolerant of treatment with FOLFOX (fluoropyrimidine and oxaliplatin) with or without Avastin (bevacizumab), will be enrolled. The trial is being conducted at two prestigious cancer centers: USC Norris Comprehensive Cancer Center and The Mayo Cancer Center.
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.