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FDA grants Fast Track Designation to Onvansertib for second-line treatment of KRAS mCRC

Tue, 06/23/2020 - 14:56
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After reviewing Cardiff Oncology’s request for Fast Track designation for onvansertib, in combination with FOLFIRI/bevacizumab, for second-line treatment of patients with KRAS-mutated metastatic colorectal cancer (mCRC), the FDA has agreed the therapy meets the criteria for a Fast Track development programme.

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 leukaemia’s, lymphomas and solid tumours. 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. Cardiff Oncology believes that targeting only PLK1 and having a favourable 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 acute myeloid leukemia (AML).

"We are very pleased with the FDA's decision to grant Fast Track designation for development of onvansertib to treat patients with KRAS-mutated mCRC," said Dr Mark Erlander, Chief Executive Officer of Cardiff Oncology. "This designation is a significant validation of not only our onvansertib clinical programme, which is now eligible for priority review and accelerated approval, but it also signifies recognition of the medical need for new effective treatment options. The efficacy of current second-line therapy in terms of response and survival prolongation remains very limited, particularly in the KRAS-mutated population, and we are confident that onvansertib, in combination with FOLFIRI/bevacizumab, represents a promising new treatment option."

Fast Track is a designation granted by the FDA that is intended to facilitate development and expedite review of drugs to address an unmet medical need in the treatment of a serious life-threatening condition, and for which nonclinical or clinical data has demonstrated the potential of the drug to address this medical need.

In an open-label, Phase 1b/2 trial, onvansertib in combination with standard-of-care FOLFIRI and Avastin (bevacizumab) is being evaluated for safety and efficacy for second-line treatment of patients with KRAS-mutated 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, will enrol 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 bevacizumab. The trial is being conducted at the USC Norris Comprehensive Cancer Center and The Mayo Clinic Arizona.

Onvansertib has previously demonstrated synergy in preclinical studies with numerous chemotherapies and targeted therapeutics used to treat leukaemia’s, lymphomas and solid tumour cancers, including irinotecan, FLT3 and HDAC inhibitors, taxanes and cytotoxins. Cardiff Oncology believes the combination of onvansertib with other compounds has the potential to improve clinical efficacy in AML, metastatic castration-resistant prostate cancer (mCRPC), non-Hodgkin lymphoma, colorectal cancer and triple-negative breast cancer (TNBC), as well as other types of cancer

Cardiff Oncology 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).

Cardiff Oncology 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.