On April 8, 2022 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, reported the results of preclinical studies evaluating the anti-cancer activity of onvansertib in combination with the PARP inhibitor (PARPi) olaparib in PARPi-resistant patient-derived xenograft (PDX) ovarian cancer models (Press release, Cardiff Oncology, APR 8, 2022, View Source [SID1234611729]). The results are featured in a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, which is taking place both virtually and in-person at the Ernest N. Morial Convention Center in New Orleans, Louisiana from April 8-13, 2022.
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"In these studies, we sought to evaluate how combining onvansertib with PARP inhibition, an approved maintenance treatment for ovarian cancer, might mitigate the known phenomenon of acquired tumor resistance to PARP inhibitors," said Tod Smeal, Ph.D., chief scientific officer at Cardiff Oncology. "We are very pleased with the results, which showed onvansertib and olaparib synergistically combining to generate strong activity against PARPi-resistant patient-derived ovarian cancer models. Given the current lack of effective treatment options for patients showing PARPi resistance, we believe these data are supportive of evaluating this combination within a PARPi-resistant clinical setting."
Preclinical studies featured in the AACR (Free AACR Whitepaper) poster evaluated onvansertib-olaparib combination treatment in three olaparib-resistant patient-derived xenograft (PDX) ovarian cancer models. Two of the three PDX models used (MNHOC22, MNHOC266) were cisplatin-sensitive with a mutated BRCA1 gene, while the third (MNHOC316DDP) was cisplatin-resistant with wild type BRCA1. BRCA1-mutant tumor cells are deficient for homologous recombination (HR)-mediated DNA repair and are initially sensitive to PARPi. This suggests that PARPi resistance was acquired in the MNHOC22 and MNHOC266 tumors due to the restoration of HR-mediated DNA repair, while being naturally conferred in MNHOC316DDP tumors due to continuous HR-proficiency.
Data showed that combining onvansertib with olaparib led to a statistically significant survival benefit compared to treatment with either agent alone in each of the three evaluated PDX models. Results showed the combination was well tolerated.
An electronic copy of the poster and corresponding abstract, entitled, Combining PARP inhibition with the Polo-like kinase 1 (PLK1) inhibitor onvansertib overcomes PARP inhibitor resistance, is available to registered attendees of the AACR (Free AACR Whitepaper) annual meeting on the meeting website. The in-person presentation will take place during the "Drug Resistance and Reversal of Resistance" poster session on April 12, 2022, from 1:30 PM – 5:00 PM CT. Following the meeting, the poster will be available on the "Scientific Presentations" section of the Cardiff Oncology website at View Source