Trovagene Inc. announced an agreement with PoC Capital to fund clinical development of onvansertib, Trovagene’s first-in-class, 3rd generation oral and highly selective Polo-like Kinase 1 inhibitor in a phase Ib/II clinical trial in patients with metastatic colorectal cancer.
Trovagene submitted an Investigational New Drug application and protocol to the FDA on Dec.19, 2018, and received a “study may proceed” notification from the FDA, 28-days later, on Jan. 16, 2019.
The trial will be conducted at two prestigious cancer centers in the U.S.; USC Norris Comprehensive Cancer Center and Mayo Clinic. Onvansertib, its lead drug candidate, is a first-in-class, 3rd generation, highly-selective oral Polo-like Kinase 1 Inhibitor. The company currently has two ongoing open-label clinical trials: a phase Ib/II trial in acute myeloid leukemia and a phase II trial in metastatic castration-resistant prostate cancer.
In this open-label, phase Ib/II trial, onvansertib in combination with standard-of-care FOLFIRI and Avastin is being evaluated for safety and efficacy. The trial, “A phase Ib/II 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”, will enroll up to 44 patients with a Kras mutation and histologically confirmed metastatic and unresectable disease.
In addition, patients must have failed treatment or be intolerant of FOLFOX (fluoropyrimidine and oxaliplatin) with or without Avastin (bevacizumab). The trial is being conducted at two prestigious cancer centers: USC Norris Comprehensive Cancer Center and The Mayo Clinic Arizona.
Onvansertib is a first-in-class, 3rd generation, oral and highly-selective adenosine triphosphate competitive inhibitor of the serine/threonine polo-like-kinase 1 enzyme, which is over-expressed in multiple cancers, including leukemias, lymphomas and solid tumors.
Separate studies with other PLK inhibitors have shown that inhibition of polo-like-kinases can lead to tumor cell death, including a phase II study in AML where response rates of up to 31% were observed when combined with a standard therapy for AML (low-dose cytarabine-LDAC) versus treatment with LDAC alone with a 13.3% response rate.
A phase I open-label, dose escalation safety study of onvansertib has been completed in patients with advanced metastatic solid tumor cancers and published in Investigational New Drugs. The maximum tolerated dose or recommended phase II dose in this trial was 24 mg/m2.
Onvansertib targets the PLK1 isoform only, is orally administered, has a 24-hour drug 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 FLT3 and HDAC inhibitors, taxanes, and cytotoxins.
Trovagene believes the combination of its targeted PLK1 inhibitor, onvansertib, with other compounds has the potential to improve clinical efficacy in AML, metastatic castration-resistant prostate cancer, non-Hodgkin lymphoma, triple negative breast cancer, as well as other types of cancer.
Trovagene has an ongoing phase Ib/II clinical trial of onvansertib in combination with low-dose cytarabine or decitabine in patients with relapsed or refractory AML that was accepted by the National Library of Medicine and is now publicly viewable on www.clinicaltrials.gov.
The NCT number assigned by clinicaltrials.gov for this study is 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 has an ongoing phase II clinical trial of onvansertib in combination with Zytiga (abiraterone acetate)/prednisone in patients with metastatic castrationrresistant prostate cancer who are showing signs of early progressive disease (rise in PSA but minimally symptomatic or asymptomatic) while currently receiving Zytiga.
The trial was accepted by the National Library of Medicine and is now publicly viewable on www.clinicaltrials.gov. The NCT number assigned by clinicaltrials.gov for this study is (NCT03414034).
