On September 8, 2021 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage oncology company, developing new precision medicine treatment options for cancer patients in indications with the greatest unmet medical need including KRAS-mutated colorectal cancer, pancreatic cancer, and castrate-resistant prostate cancer, reported new data from its lead clinical program evaluating onvansertib in combination with standard-of-care (SOC) FOLFIRI/bevacizumab for second-line treatment of patients with KRAS-mutated metastatic colorectal cancer (mCRC) (Press release, Cardiff Oncology, SEP 8, 2021, View Source [SID1234587440]).

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"Our Phase 1b/2 trial continues to generate data suggesting that the addition of onvansertib to SOC results in an objective response rate and median progression-free survival that substantially exceed those previously achieved with SOC alone," said Katherine L. Ruffner, M.D., chief medical officer of Cardiff Oncology. "Radiographic responses have been observed across multiple KRAS mutation variants, which speaks to a key advantage of onvansertib over competing agents targeting individual mutations. These impressive results, which have remained consistent across both academic and community trial sites, highlight the potential for onvansertib to address the unmet need for new second-line therapeutic options to treat patients with KRAS-mutated mCRC. I look forward to the trial’s continued advancement and future data readouts."

Highlights from today’s data announcement include:

Efficacy data in patients evaluable for disease response as of data cutoff date (July 2, 2021):

Patients treated per protocol at the recommended Phase 2 dose (RP2D; 15 mg/m2) across both Phase 1b and Phase 2:
8 of 19 (42%) achieved an initial partial response (PR) as of the data cutoff date
7 of 19 (37%) have achieved a confirmed PR (based on further follow-up of patients with an initial PR as of data cutoff date)
Objective response rates observed in historical control trials in similar patient populations treated with standard of care are 5-13%1-4

Patients evaluable for response treated at all dose levels (12 mg/m2, 15 mg/m2, 18 mg/m2) across both phases of the study
12 of 32 (38%) achieved an initial PR as of the data cutoff date
10 of 32 (31%) have achieved a confirmed PR (based on further follow-up of patients with an initial PR as of data cutoff date)
Median progression free survival (mPFS)

mPFS has not yet been reached in patients treated per protocol at the RP2D
mPFS across all response-evaluable patients (n = 32) is 9.4 months (95% confidence interval: 7.8 – not yet reached)
mPFS of ~4.5-5.7 months has been reported in trials used as historical controls1-4
Biomarker data as of data cutoff date across all patients:

Partial responses (PRs) were observed across different KRAS mutation variants, including the 3 most common observed in colorectal cancer (G12D, G12V, G13D)
Patients achieving a best response of PR showed the greatest decreases in plasma KRAS mutant allelic frequency (MAF) after 1 cycle (28 days) of therapy
Safety data as of data cutoff date across all patients:

The combination of onvansertib and FOLFIRI/bevacizumab was shown to be well-tolerated with only 10% (49/490) of reported treatment-emergent adverse events (TEAEs) being G3/G4
Most reported treatment-related adverse events (TRAEs) were manageable and reversible with supportive care
Mark Erlander, Ph.D., chief executive officer of Cardiff Oncology, commented, "The strong signal of efficacy and favorable tolerability profile observed in this trial bodes well not only for our lead mCRC program, but for each of our KRAS-focused clinical programs. The meaningful improvements we are seeing in treatment response relative to historical controls demonstrate the value of combination therapy and support the synergistic effect observed preclinically when onvansertib is added to standard-of-care irinotecan and 5-FU (FOLFIRI). We are also seeing compelling biomarker results that highlight the potential utility of plasma KRAS MAF as a predictive tool that could aid in the design of subsequent trials. Looking forward, we anticipate the ongoing Phase 2 portion of the trial to provide additional data catalysts that will advance the clinical development of onvansertib, generate value for shareholders and, most importantly, provide new treatment options for patients."

Key Opinion Leader Webinar
The newly announced data are being discussed today at 4:00 PM ET as part of a key opinion leader (KOL) webinar being hosted by Cardiff Oncology. The webinar is featuring the clinical trial principal investigator, Heinz-Josef Lenz, M.D., FACP, USC Norris Comprehensive Cancer Center, key clinical advisor Afsaneh Barzi, M.D., Ph.D., City of Hope Comprehensive Cancer Center, and members of the Cardiff Oncology management team.

To attend the webinar, click here. A replay of the webinar will be available by visiting the "Events" section of the Cardiff Oncology website shortly after its conclusion.

About the Phase 1b/2 Trial of Onvansertib in KRAS-mutated mCRC
This is a multi-center, single-arm, 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, is enrolling patients with histologically confirmed metastatic and unresectable colorectal carcinoma harboring a KRAS mutation. Patients must also have failed treatment with, or be intolerant to, FOLFOX (fluoropyrimidine and oxaliplatin) with or without bevacizumab to be eligible. The trial is being conducted at the following cancer centers across the U.S.: USC Norris Comprehensive Cancer Center, The Mayo Clinic (Arizona, Rochester, and Jacksonville), Kansas University Medical Center (KUMC), CARTI Cancer Center and Inova Schar Cancer Institute. For more information on the trial, please visit View Source

References

Giessen et al., Acta Oncologica 2015, 54: 187-193
Cremolini et al., Lancet Oncol 2020, 21: 497–507
Antoniotti et al., Correspondence Lancet Oncol June 2020
Bennouna et al., Lancet Oncol 2013; 14: 29–37