Cardiff Oncology, Inc., a clinical-stage oncology therapeutics company developing drugs to treat cancers with the greatest medical need for new treatment options, including KRAS-mutated colorectal cancer, Zytiga®-resistant prostate cancer and leukemia, today announced that the U.S. Food and Drug Administration (FDA) granted Fast Track Designation to onvansertib, its oral and highly-selective Polo-like Kinase 1 (PLK1) inhibitor, for the second-line treatment of patients with KRAS-mutated metastatic colorectal cancer (mCRC).
"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 program, 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.
A drug that receives Fast track Designation is eligible for some, or all, of the following:
- Eligibility for accelerated approval and priority review, if relevant criteria are met
- Rolling review, enabling Cardiff Oncology to submit completed sections of its New Drug Application (NDA) for review by the FDA, rather than waiting until every section of the NDA is completed before the entire application can be reviewed (NDA review usually does not begin until the Company has submitted the entire NDA to the FDA)
- More frequent meetings with the FDA to discuss the drug's development plan and ensure collection of appropriate data to support drug approval
- More frequent written communication from the FDA about such things as the design of the proposed clinical trials and use of biomarkers
About the Phase 1b/2 Clinical Trial of Onvansertib in KRAS-Mutated mCRC
In this 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 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 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, 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. Cardiff Oncology 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. Cardiff Oncology 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.
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).
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