Trovagene 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 (PLK1) inhibitor in a Phase 1b/2 clinical trial in patients with metastatic Colorectal Cancer (mCRC). Trovagene submitted an Investigational New Drug (IND) application and protocol to the FDA on December 19, 2018, and received a "study may proceed" notification from the FDA, 28-days later, on January 16, 2019. The trial will be conducted at two prestigious cancer centers in the U.S.; USC Norris Comprehensive Cancer Center and The Mayo Clinic.
"We are excited to provide investment to support additional clinical trials for Trovagene's PLK1 inhibitor, Onvansertib," said Daron Evans, Managing Director of PoC Capital. "Patients need as many treatment options as possible to keep cancer in remission. Early data suggests that Onvansertib works synergistically with multiple approved treatments in a number of different cancer types, and that biomarkers may help identify patients most likely to respond to treatment. That lines up as a win-win-win for patients, doctors and payors."
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"Our agreement with PoC Capital is an important milestone achievement and allows us to further the clinical development of Onvansertib in an indication of high unmet medical need in mCRC," said Dr. Thomas Adams, Chief Executive Officer and Chairman of Trovagene. "Approximately half of mCRC patients have a highly aggressive tumor that harbors the deleterious KRAS mutation which has been previously non-druggable and therefore treating this patient population has been challenging. Our preclinical in-vitro and in-vivo data indicates that tumors harboring KRAS mutations are more sensitive to Onvansertib-induced tumor death. Furthermore, Onvansertib has significant synergy in combination with Camptosar (irinotecan), as well as Avastin (bevacizumab), both of which are components of the standard of care treatment regimen that will be used in our trial. We believe Onvansertib in combination with standard of care could yield important clinical benefit to patients who otherwise have limited therapeutic options."
Colorectal cancer (CRC) is the second leading cause of cancer mortality in the U.S. Despite progress in the treatment of mCRC, the majority of patients with metastatic disease succumb to the disease. Therefore, improving the treatment options and effectiveness is critical in changing the outcomes for this patient population. KRAS is a common mutation in the CRC population and approximately 50% of patients with CRC carry RAS mutations. In the U.S., FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) and FOLFIRI (fluorouracil, leucovorin, irinotecan) are standard-of-care options for patients with metastatic CRC in the first-line setting, irrespective of the Kras mutation status. The majority of CRC patients respond to first-line therapy with a response rate of > 50%. The efficacy of second-line therapy in terms of survival prolongation and response remains very limited, particularly in the Kras-mutated population, where treatment options are more restricted. FOLFIRI (a chemotherapy regimen of irinotecan, fluorouracil [5-FU], and leucovorin) + Avastin (bevacizumab) in the second-line setting is the standard treatment in US. The response rate in the second-line setting is less than 5% as reported in a large international trial of bevacizumab in the second-line setting. This is a significant opportunity for Onvansertib to provide clinical benefit for patients who are faced with a poor prognosis and who have limited therapeutic options.
In this open-label, Phase 1b/2 trial, Onvansertib in combination with standard-of-care FOLFIRI and Avastin is being evaluated for safety and efficacy. 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, 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).