Cardiff Oncology, Inc. 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. 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. 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). 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. 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.