On January 15, 2021 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, reported 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 (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO-GI), and provided an additional data update from its mCRC clinical program and initial findings from its Expanded Access Program (Press release, Cardiff Oncology, JAN 15, 2021, View Source [SID1234574050]).

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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 (Free ASCO Whitepaper)-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 (Free ASCO Whitepaper)-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
Biomarker Analyses:

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)
Safety:

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
The 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), will be available on the "Scientific Presentations" section of the Cardiff Oncology website at View Source

About the Phase 1b/2 Trial of Onvansertib in KRAS-mutated mCRC

This is a multi-center, open-label Phase 1b/2 trial of onvansertib in combination with standard-of-care FOLFIRI and Avastin (bevacizumab) to evaluate the safety and preliminary efficacy of the combination regimen in the second-line treatment of patients with KRAS-mutated mCRC. The trial, A Phase 1b/2 Study of Onvansertib (PCM-075) in Combination with FOLFIRI and Bevacizumab for Second–Line Treatment of Metastatic Colorectal Cancer in Patients with a KRAS Mutation, will enroll up to 44 patients with a KRAS mutation and histologically confirmed metastatic and unresectable disease. In addition, eligible patients must have failed treatment with, or be intolerant to, FOLFOX (fluoropyrimidine and oxaliplatin) with or without bevacizumab. The trial is being conducted at six cancer centers across the U.S.: USC Norris Comprehensive Cancer Center, The Mayo Clinic (Arizona, Rochester and Jacksonville), Kansas University Medical Center (KUMC) and CARTI Cancer Center. For more information on the trial, please visit View Source

About the Expanded Access Program (EAP) for Onvansertib in KRAS-mutated mCRC

Sometimes called "compassionate use", expanded access is a potential pathway for a patient with a serious or life-threatening disease to gain access to an investigational drug for treatment outside of a clinical trial, particularly when no comparable or satisfactory alternative therapy options are available. The Cardiff Oncology EAP in KRAS-mutated mCRC is using the same combination treatment regimen (onvansertib 15 mg/m2 + FOLFIRI/bevacizumab) and dosing schedule as the ongoing Phase 1b/2 clinical trial and is intended for patients that have progressed on prior therapy and do not meet the eligibility criteria for enrollment in the clinical trial. Requests for expanded access to onvansertib must be made by a U.S. licensed, treating physician. For more information on the expanded access program, please visit View Source