On October 22, 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 data demonstrating positive response to treatment in patients enrolled in its Phase 1b/2 trial of onvansertib in combination with FOLFIRI and Avastin (bevacizumab) for second-line treatment of KRAS-mutated metastatic colorectal cancer (mCRC) (Press release, Trovagene, OCT 22, 2019, View Source [SID1234542425]). Decreases in tumor KRAS mutational burden in response to treatment was observed in all four patients who completed their first cycle of therapy with the combination regimen, as measured by quantitative analysis of circulating tumor DNA (ctDNA).
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!
Colorectal cancer (CRC) is the second leading cause of cancer mortality in the U.S. Despite significant progress in the treatment of mCRC, the majority of patients succumb to the disease. Therefore, improving the effectiveness of treatments is critical to changing the outcomes for this patient population. Approximately 50% of mCRC patients have the KRAS mutation. The efficacy of current second-line therapy in terms of survival prolongation and response remains very limited, especially in this population, where there is only a 5% response rate.
"We are pleased by the early indication of response to treatment with the addition of onvansertib to standard-of care in patients with KRAS-mutated mCRC," said Dr. Thomas Adams, Chief Executive Officer and Chairman of Trovagene. "We believe the combination of onvansertib and FOLFIRI/bevacizumab has the potential to provide a much-needed safe and effective new treatment option for the approximately 50% of patients with KRAS-mutated mCRC."
"Although still early in the trial, we are encouraged by the decreases in KRAS, assessed following initial dosing with onvansertib in combination with FOLFIRI/ bevacizumab, in patients treated in the first cohort," said lead investigator Dr. Afsaneh Barzi, associate professor of clinical medicine at Keck School of Medicine of USC and medical oncologist at USC Norris Comprehensive Cancer Center. "Additionally, these patients have continued on treatment beyond the cycle 1 safety assessment, indicating that the regimen appears to be safe and well tolerated. These initial findings suggest that onvansertib may provide clinical benefit for mCRC patients who have limited therapeutic options and a poor prognosis."
An overview of the mCRC Phase 1b/2 clinical trial (NCT03829410) was also featured in a poster presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Congress in September 2019. The presentation included the supportive preclinical data, demonstrating synergy with the combination of onvansertib and irinotecan, a key component of the FOLFIRI regimen.
About the Phase 1b/2 Clinical Trial of Onvansertib in mCRC
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 Clinic Arizona.
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 2 clinical trial of onvansertib in combination with decitabine in patients with relapsed or refractory AML (NCT03303339).
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.