TrovaGene, Inc. Announces Positive Data from an Ongoing Phase 1B/2 Clinical Trial of Onvansertib Plus Folfiri and Avastin® for Second-Line Treatment of Kras-Mutated Metastatic Colorectal Cancer
January 27, 2020 at 08:00 am
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Trovagene, Inc. announced positive data from an ongoing Phase 1b/2 clinical trial of onvansertib plus FOLFIRI and Avastin® (bevacizumab) for second-line treatment of KRAS-mutated metastatic colorectal cancer (mCRC). The data demonstrate the pan-KRAS inhibitory effect of onvansertib. All five patients evaluable for efficacy assessment have shown a significant reduction in their KRAS mutational burden as measured by a simple blood test, which was subsequently confirmed by tumor regression visible on radiographic scans. Three patients had a >25% tumor shrinkage and one patient is now eligible for curative surgery, a clinically meaningful achievement, which is considered to be unprecedented in this patient population with only a 5% response to standard-of-care. The data was featured in a poster presentation at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO-GI) in San Francisco on Saturday, January 25th, 2020. Onvansertib is an oral and highly-selective Polo-like Kinase 1 (PLK1) inhibitor and may provide an answer to effectively "drugging" the once thought-to-be "undruggable" KRAS mutation. PLK1 has been identified as having synthetic lethality, which means that KRAS-mutated tumors have a higher sensitivity to PLK1 inhibition compared with KRAS wild-type cells. KRAS, which controls cell proliferation, has long been recognized as a major oncogene, responsible for many cancer types. 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. The other KRAS contenders including Amgen and Mirati, have produced some potentially promising early clinical results in non-small cell lung cancer (NSCLC); however, their drug candidates have shown limited activity in CRC as they only address one specific KRAS mutation, G12C, which accounts for only 8% of CRC, leaving room for drug developer, Trovagene, and its drug candidate onvansertib. Onvansertib KRAS-Mutated mCRC Trial Data Highlights: In the Phase 1b dose escalation, the 1st dose level (onvansertib 12 mg/m2) was cleared for safety; the 2nd dose level (onvansertib 15 mg/m2) is fully enrolled with no DLTs reported in the two patients treated to-date. Radiographic scans performed at 8 weeks showed tumor decrease and clinical benefit in 100% (n=5) of evaluable patients treated with onvansertib 12 mg/m2 (n=5); 1 patient achieved PR, 4 patients achieved SD. Radiographic responses were confirmed at 16 weeks with further tumor shrinkage in all patients; 3 patients had a >25% decrease; 1 patient is proceeding to curative surgery. Five different KRAS mutant variants were detected in 6 patients, which represents >90% of KRAS mutations in CRC; all five KRAS variants decreased within the 1st cycle of treatment (onvansertib dose levels 12 and 15 mg/m2). At dose level 1 (onvansertib 12 mg/m2), 4 patients had detectable KRAS mutant ctDNA at baseline; in all 4 patients KRAS was undetectable within the 1st cycle of treatment; this preceded subsequent tumor shrinkage observed with radiographic scans, supporting the predictive value of liquid biopsy. At dose level 2 (onvansertib 15 mg/m2), the 2 patients treated to-date had detectable KRAS mutant ctDNA at baseline; in 1 patient KRAS was undetectable within the 1st cycle of treatment; radiographic scans will be performed at 8 weeks.
Cardiff Oncology, Inc. is a clinical-stage biotechnology company. It is leveraging PLK1 inhibition, a well-validated oncology drug target, to develop novel therapies across a range of cancers with the unmet medical need. It is focused on clinical programs in indications, such as RAS-mutated metastatic colorectal cancer (mCRC), and in investigator-initiated trials in metastatic pancreatic ductal adenocarcinoma (mPDAC), small cell lung cancer (SCLC), and triple negative breast cancer (TNBC). Its lead drug candidate, Onvansertib, is an oral, small molecule drug candidate that is highly specific for PLK1 inhibition with a 24-hour half-life. It has five ongoing and planned clinical trials of onvansertib: one trial (CRDF-004) in first-line treatment in patients with RAS-mutated mCRC, one trial (CRDF-001) in second-line treatment in patients with mPDAC, and three investigator-initiated trials in first line mPDAC, relapsed SCLC and unresectable locally advanced or metastatic TNBC.
TrovaGene, Inc. Announces Positive Data from an Ongoing Phase 1B/2 Clinical Trial of Onvansertib Plus Folfiri and Avastin® for Second-Line Treatment of Kras-Mutated Metastatic Colorectal Cancer