Benzinga | Jan 18, 2022 05:02PM EST

Cardiff Oncology Announces New Data From Lead Clinical Program In KRAS-Mutated Metastatic Colorectal Cancer Showing Robust Objective Response Rate And Progression Free Survival

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, today announced 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). A subset of these data will be featured in a poster presented by Dr. Heinz-Josef Lenz, principal investigator, USC Norris Comprehensive Cancer Center, at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCOGI) on Saturday, January 22, 2022.

"As we have increased the number of patients evaluated and the duration of follow-up, our Phase 1b/2 trial has consistently generated data suggesting that onvansertib provides meaningful clinical benefits when added to SOC," said Katherine L. Ruffner, M.D., chief medical officer of Cardiff Oncology. "The objective response rate and median progression free survival observed substantially exceed what would be expected with SOC alone, and five patients receiving onvansertib have been able to pursue potentially curative metastasis-directed treatments. We also observed a confirmed complete response, which is exciting given the difficult-to-treat nature of second line mCRC patients."

The most current data for the trial are shown below and include patient follow up collected after the cutoff dates for both the ASCO-GI abstract and poster (one additional PR was recorded after December 3):

Efficacy data in evaluable patients (represents an update from ASCO-GI abstract/poster):

* Among patients treated per protocol at the recommended Phase 2 dose (RP2D; 15 mg/m2) in combination with FOLFIRI-bev: 12 of 35 (34%) achieved an initial complete response (CR) or partial response (PR) 10 of 35 (29%) achieved a confirmed CR or PR (awaiting confirmatory scan for 1 patient) 33 of 35 (94%) had a best response of disease control (CR + PR + SD) Objective response rates of 5-13% observed in historical control trials in similar patient populations treated with various different drug combinations, including the standard of care chemotherapy of FOLFIRI with bevacizumab1-4

* Patients evaluable for response treated at all dose levels (12 mg/m2, 15 mg/m2, 18 mg/m2) 17 of 48 (35%) achieved an initial CR or PR 13 of 48 (27%) have achieved a confirmed CR or PR (awaiting confirmatory scan for 1 patient) 44 of 48 (92%) had a best response of disease control (CR + PR + SD)

* Status of 4 unconfirmed PRs: 1 patient discontinued from the trial prior to confirmatory scan due to an adverse event that was unrelated to treatment (hepatitis B) 1 patient went from PR to SD at the confirmatory scan and patient subsequently discontinued from the trial to pursue potentially curative metastasis-directed therapy 1 patient went from PR to SD at the confirmatory scan (patient remains on treatment) 1 patient has yet to have their confirmatory scan

* 5 of 48 (10%) evaluable patients discontinued therapy to pursue potentially curative metastasis-directed therapy (surgery or microwave ablation), including 2 patients with SD

Median progression free survival (mPFS; no update from ASCO-GI poster)

* mPFS has not yet been reached in patients treated per protocol at the RP2D

* mPFS across all response-evaluable patients (n = 48) is 9.4 months (95% confidence interval: 7.1 -- not yet reached)

* mPFS of ~4.5-5.7 months has been reported in trials used as historical controls1-4

Biomarker data across all patients (no update from ASCO-GI poster):

* Responses (CRs or PRs) were observed across seven different KRAS mutation variants, including the 3 most commonly observed in colorectal cancer (G12D, G12V, G13D)

* Patients achieving a best response of a CR or PR showed the greatest decreases in plasma KRAS mutant allelic frequency (MAF) measured by droplet digital PCR (ddPCR) after 1 cycle (28 days) of therapy

Safety data across all patients (no update from ASCO-GI poster):

* The combination of onvansertib and FOLFIRI/bevacizumab was shown to be well-tolerated with only 11% (84/788) of reported treatment-emergent adverse events (TEAEs) being G3/G4 The most commonly reported adverse event was neutropenia/neutrophil count decreased Most reported TEAEs were manageable and reversible with supportive care

Baseline characteristics of patients at all dose levels (no update from ASCO-GI poster):

* The patients' median age was 61 years (range 35-83), and 56% were male

* 67% patients had previously received bevacizumab

* 16 of 48 (33%) evaluable patients remain on trial at the data cutoff date

Mark Erlander, Ph.D., chief executive officer of Cardiff Oncology, commented, "These impressive results show radiographic responses across multiple KRAS mutation variants when onvansertib is combined with the standard of care regimen of FOLFIRI-bev and demonstrate a substantial increase in disease response relative to historical controls. We believe the data presented today further validate the potential of onvansertib to provide a meaningful improvement in the treatment outcome of a large patient population that has limited available treatment options. Looking forward, and with our strong cash position, we have the ability to explore the full potential of onvansertib."