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 updated clinical data and new biomarker analyses from its ongoing Phase 2 trial of onvansertib in combination with abiraterone/prednisone in metastatic castrate-resistant prostate cancer (mCRPC) patients (Press release, Cardiff Oncology, APR 8, 2022, View Source [SID1234611704]). The data 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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"Results from the mCRPC trial demonstrate clinically meaningful disease control rates in patients showing early resistance to abiraterone," said David Einstein, M.D., principal investigator at Beth Israel Deaconess Medical Center. "As the dose density of onvansertib was increased in three consecutive Arms (A, B and C), we observed an increase in disease control rates with both PSA stabilization and radiographic stable disease twelve weeks into treatment and some of these patients have experienced durable stabilization. Pre-clinical data suggest that the synergistic effect is independent of androgen receptor signaling."
The primary efficacy endpoint of the mCRPC trial is disease control rate at 12 weeks (12-week DCR), which is defined by a decline or stabilization of PSA levels (rise of <25% over baseline or less than 2 ng/mL). Each of the trial’s three arms has evaluated a different dosing schedule of onvansertib alongside abiraterone and prednisone administered throughout the respective treatment cycle. Arm A evaluated 24 mg/m2 onvansertib on Days 1-5 of 21-day cycles, Arm B evaluated 18 mg/m2 onvansertib on Days 1-5 of 14-day cycles, and Arm C is evaluating 12 mg/m2 onvansertib on Days 1-14 of 21-day cycles.
"Biomarker correlative studies have revealed significant and positively associated mutations in MTOR, FAT1, PTEN and FOXA1, with tumors harboring these mutations achieving stable disease or a partial response within the initial abiraterone-resistant setting," said Tod Smeal, Ph.D., chief scientific officer of Cardiff Oncology. "In addition, gene expression signatures from patient tumor tissue biopsies correlated with treatment response included those corresponding to the ERG+ and Notch pathways, which are involved in cell-invasion, epithelial-mesenchymal transition and metastasis. We continue to examine these promising biomarker studies with the goal of identifying the genomic alterations most closely associated with response to the combination regimen of onvansertib and abiraterone."
Key data and conclusions from the AACR (Free AACR Whitepaper) poster (cut-off date of February 2, 2022) and ongoing trial include:
Efficacy:
75% (15/20) of evaluable patients in Arm C, which represents the most dose dense treatment schedule, showed disease control by radiographic SD/PR at 12-weeks, compared to 53% (9/17) and 58% (11/19) in the less dose dense Arms A and B, respectively
Biomarker:
Treatment response (SD/PR) was positively associated with mutations in PTEN and MTOR, key genes in the PI3K signaling pathway
Gene signatures correlating with treatment response included those corresponding to the ERG+ and Notch pathways, which are involved in cell-invasion, epithelial-mesenchymal transition and metastasis
Genes related to mitochondrial and immune functions were downregulated in patients achieving SD or a PR compared to those showing progressive disease
Safety:
The treatment regimen of onvansertib in combination with abiraterone/prednisone has been well tolerated
An electronic copy of the poster and corresponding abstract, entitled, Biomarkers of response to abiraterone and the polo-like kinase 1 (PLK1) inhibitor onvansertib in metastatic castration resistant prostate cancer (mCRPC) patients, 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 "Biomarkers Predictive of Therapeutic Benefit 1" poster session on April 11, 2022, from 9:00 AM – 12:30 PM CT. Following the meeting, the poster will be available on the "Scientific Presentations" section of the Cardiff Oncology website at View Source