On February 11, 2021 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company developing drugs to treat cancers with the greatest medical need for new treatment options, including KRAS-mutated colorectal cancer, pancreatic cancer, castrate-resistant prostate cancer and leukemias, reported that updated data from its Phase 2 metastatic castrate-resistant prostate cancer (mCRPC) trial were featured in a virtual oral poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO-GU) (Press release, Cardiff Oncology, FEB 11, 2021, View Source [SID1234574914]). The ongoing Phase 2 trial evaluates the all-oral combination of onvansertib, abiraterone and prednisone in patients showing initial abiraterone resistance, as defined by two consecutive rises in prostate-specific antigen (PSA) levels.

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Newly presented data from the Phase 2 mCRPC trial showed that increasing the number of days of treatment with onvansertib from 5 to 14 in a 21-day cycle was associated with a greater than two-fold increase (29% to 63%) in disease control rate (DCR; defined by lack of PSA progression) at 12 weeks, the trial’s primary efficacy endpoint. Six of eight (75%) evaluable patients receiving onvansertib for 14 of 21 days per cycle had stable disease upon radiographic scan at 12 weeks and five of these patients remain on treatment to-date. Across all cohorts, the DCR at 12 weeks is 35% (13/37), indicating the trial is on track to meet the stated criteria for success on its primary efficacy endpoint (30% DCR at 12 weeks).

"The preliminary data presented at ASCO (Free ASCO Whitepaper)-GU support a clinically meaningful onvansertib exposure effect," said David Einstein, M.D., attending physician at Beth Israel Deaconess Medical Center and principal investigator of the onvansertib mCRPC Phase 2 trial. "In the first eight patients treated to-date on Arm C, we are excited to see an increase in DCR with greater time on onvansertib, without excessive toxicity. Together with the clinically meaningful rates of disease control, and duration of disease control, we are seeing across all cohorts, these data demonstrate onvansertib’s potential to address a critical unmet need for patients with abiraterone-resistant mCRPC."

"As data from this trial continue to emerge, we are very pleased to see increased efficacy with an optimized dosing schedule that is both well tolerated and increases the number of days a patient receives onvansertib in combination with abiraterone by nearly 3-fold" said Mark Erlander, Ph.D., chief executive officer of Cardiff Oncology. "These data suggest that the synergy demonstrated between onvansertib and abiraterone in pre-clinical models is being observed clinically. The trial’s biomarker analyses are also promising, as the identification of mutations associated with response to the combination of onvansertib and abiraterone may enable more efficient design of future clinical studies and the identification of patients most likely to benefit from this combination."

Key data and conclusions from the ASCO (Free ASCO Whitepaper)-GU presentation include:

Efficacy:

The optimized dosing schedule of cohort C shows a greater than two-fold improvement in disease control rate compared to cohorts A and B
63% (5/8) of cohort C patients achieved the primary efficacy endpoint compared to 29% (5/17) and 25% (3/12) of cohort A and B patients, respectively
75% (6/8) of evaluable patients in cohort C had radiographic SD at 12 weeks, compared to 53% (9/17) in cohort A, 42% (5/12) in cohort B and 54% (20/37) across all cohorts
All cohort C patients achieving the primary efficacy endpoint remain on treatment
35% (13/37) of evaluable patients across all cohorts (A-C) achieved the primary efficacy endpoint of disease control at 12 weeks
Efficacy was observed in patients harboring androgen receptor (AR) alterations associated with abiraterone resistance across all 3 arms
Biomarker:

Circulating tumor DNA (ctDNA) analysis revealed differences in baseline genomic profiles of patients achieving SD at 12 weeks vs. those progressing at or before 12 weeks
Mutations present exclusively in patients with SD at 12 weeks were associated with cell cycle and DNA repair pathways that may result in increased efficacy of the onvansertib-abiraterone combination
Safety:

Data show that the combination of onvansertib and abiraterone is well tolerated across the three different dosing schedules of cohorts A-C:
Cohort A: 24 mg/m2 onvansertib on Days 1-5 of 21-day cycles, plus abiraterone and prednisone beginning on Day 1 and continuing uninterrupted throughout each cycle
Cohort B: 18 mg/m2 onvansertib on Days 1-5 of 14-day cycles, plus abiraterone and prednisone beginning on Day 1 and continuing uninterrupted throughout each cycle
Cohort C: 12 mg/m2 onvansertib on Days 1-14 of 21-day cycles, plus abiraterone and prednisone beginning on Day 1 and continuing uninterrupted throughout each cycle
The virtual poster, A Phase 2 Study of the Polo-like Kinase 1 (PLK1) Inhibitor Onvansertib in Combination with Abiraterone and Prednisone in Patients with Metastatic Castration-Resistant Prostate Cancer (mCRPC), is available on the "Scientific Presentations" section of the Cardiff Oncology website at View Source

About the Phase 2 Trial of Onvansertib in Metastatic Castration-Resistant Prostate Cancer
This trial is a Phase 2 open-label study of onvansertib in combination with abiraterone and prednisone, all administered orally, in patients with metastatic castration-resistant prostate cancer showing signs of early progressive disease (demonstrated by two rising prostate-specific antigen values separated by at least one week with no or minimal symptoms) while on Zytiga/prednisone therapy. The primary efficacy endpoint is the proportion of patients achieving disease control after 12 weeks of study treatment, as defined by a lack of prostate-specific antigen (PSA), radiographic, or symptomatic progression. The trial is being conducted by Beth Israel Deaconess Medical Center (BIDMC), Dana-Farber Cancer Institute (Dana-Farber), and Massachusetts General Hospital Cancer Center (MGH). David Einstein, M.D., Genitourinary Oncology Program at BIDMC, is the principal investigator for the trial. For more information on the trial, please visit View Source