Cardiff Oncology Presents Data that Continues to Demonstrate the Clinical Benefit of Onvansertib in KRAS-Mutated mCRC and Initial Findings from its Expanded Access Program
Of the 12 Phase 1b patients evaluable for efficacy as of the ASCO-GI data cut-off date (November 1, 2020), 5 (42%) achieved a partial response (PR) and 8 (67%) have shown a durable response ranging from 6.1 to 13.7 months
- Since the ASCO-GI data cut-off date, 2 additional Phase 1b patients have had their initial 8-week scan showing stable disease (SD) and both remain on treatment to-date
- Time to achieving a PR ranges from 2 to 6 months in patients on treatment
- The recommended Phase 2 dose (RP2D) of onvansertib has been established at 15mg/m2 and the Phase 2 segment of the ongoing trial is open to full enrollment of 26 patients across 6 sites in the U.S.
- In the Expanded Access Program (EAP), 6 (66%) of the initial 9 patients treated have shown tumor shrinkage and remain on treatment to-date with durable responses lasting an average of 6 months; 5 different KRAS mutation subtypes are represented (G12A, G12C, G12V, G13D, A146T); all patients had received prior treatment with FOLFIRI
- Decreases in the KRAS mutational burden in patients after the first cycle of treatment have been predictive of subsequent tumor shrinkage in both the clinical trial and EAP
Cardiff Oncology, Inc. (Nasdaq:?CRDF), a clinical-stage biotechnology company developing new treatment options for cancer patients in indications with the greatest medical need, including KRAS-mutated colorectal cancer, castration-resistant prostate cancer and leukemia, today announced the presentation of data from its Phase?1b/2 study in KRAS-mutated metastatic colorectal cancer (mCRC) as part of the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO-GI), and provided an additional data update from its mCRC clinical program and initial findings from its Expanded Access Program. Enrollment of patients in the Phase?1b?segment of the Phase?1b/2 KRAS-mutated mCRC trial is complete and the recommended Phase 2 dose (RP2D) of onvansertib has been confirmed at 15 mg/m2. The Phase 2 segment of the trial is open to full enrollment of approximately 26 patients across 6 trial sites:?USC?Norris Comprehensive Cancer Center, Mayo Clinic Cancer Centers (Arizona, Rochester, Jacksonville),?Kansas University?Medical Center and CARTI Cancer Center. "The Phase?1b?data show that a significant percentage of patients had tumor shrinkage, achieved clinical benefit and, importantly, that the response appears durable with two-thirds of the patients having been on treatment for at least six months," said?Daniel H. Ahn, D.O., lead investigator and medical oncologist, Mayo Clinic Cancer Center,?Arizona. "This highlights the promise of onvansertib plus standard-of-care as an effective second-line treatment for patients with KRAS-mutated mCRC. We look forward to building on these promising data during the Phase 2 portion of the trial." Initial findings from Cardiff Oncology's EAP for onvansertib in KRAS-mutated mCRC are similar to results from the Phase?1b?trial. In the EAP, 6 (66%) of the first 9 patients treated have shown tumor shrinkage?and remain on treatment to-date with durable responses lasting an average of 6 months. Additionally, 5 different KRAS mutation subtypes are represented (G12A, G12C, G12V, G13D, A146T) and all patients had received prior treatment with FOLFIRI. Importantly, decreases in the KRAS mutational burden after the first cycle of treatment have been predictive of subsequent tumor shrinkage. "We are pleased with the continued advancement of our KRAS-mutated mCRC clinical study and are excited to initiate enrollment in the Phase 2 segment of this trial," said Dr.?Mark Erlander, chief executive officer of Cardiff Oncology. "Additionally, our EAP is being very well received by clinicians and patients who would otherwise not have access to onvansertib because they don't meet the strict eligibility criteria for our trial. We are encouraged by the initial observations and, in particular, the duration of response we are seeing, which is consistent with the data from our clinical trial. Of note, the key difference in the patients enrolled in our EAP is that several had received and progressed on prior FOLFIRI-based treatment and with the addition of onvansertib we are seeing tumor shrinkage and durable stable disease." The Phase?1b?data will be featured in a poster,?A phase Ib/II study of the polo-like kinase 1 (PLK1) inhibitor, onvansertib, in combination with FOLFIRI and bevacizumab for second-line treatment of patients with KRAS-mutated metastatic colorectal Cancer (mCRC), presented by Dr.?Daniel Ahn?and streamed virtually at ASCO-GI on?January 15th?from?8:00 am???6:15 pm ET?during the Trials in Progress Poster Session: Colorectal Cancer (Abstract TPS155). Highlights from the Poster Presentation: Efficacy:- Of the 12 evaluable patients as of the ASCO-GI data cut-off date, 5 (42%) achieved a partial response (PR); 4 patients had a confirmed PR; 1 patient went on to curative surgery; 1 patient with a non-confirmed PR went off study due to an unrelated event prior to their 16-week confirmatory scan
- Time to achieving a PR ranges from 2 to 6 months in patients on treatment
- 8 (67%) showed durable responses of >6 months with a range from 6.1 to 13.7 months
- 10 of 12 patients had a KRAS variant detected by ddPCR at baseline (all had a KRAS mutation detected by NGS)
- Clinical responses were observed across different KRAS variants, including the 3 most common in CRC
- The greatest decreases in KRAS mutant allelic frequency (MAF) after 1 cycle of treatment were observed in patients achieving a PR (ranging from -78% to -100%), while the 2 patients who progressed showed a more modest reduction in KRAS MAF (-55% and -26%)
- Patients with PR and stable disease (SD) tended to have lower on-treatment KRAS MAF than patients with early progressive disease (PD)
- Onvansertib in combination with FOLFIRI/bevacizumab is safe and well tolerated with only 9% of all adverse events (AEs) being grade 3 or 4
- Grade 4 adverse events were attributed to the 5-FU bolus component of the combination regimen, which was eliminated in subsequent cycles of treatment per protocol and institutional guidelines
- The only G3/G4 AEs reported in =2 patients were neutropenia (n=8), which were managed by dose delay, growth factor therapy and/or discontinuation of the 5-FU bolus; no patients went off trial due to neutropenia
- No major or unexpected toxicities were attributed to onvansertib