Turning the Tide
on KRAS-Mutated Metastatic Colorectal Cancer (mCRC)
Onvansertib in Combination with Second-Line Standard-of-Care is Reducing Tumor Growth and Increasing Progression-Free Survival
Improving response to second-line treatment and increasing progression-free survival
There is currently only a 4% response rate to second-line standard-of-care (SOC) FOLFIRI/Avastin® and median progression-free survival (PFS) of 5.5 months.
Onvansertib in combination with standard-of-care is a promising new second-line therapy to improve response to treatment and increase progression-free survival.
KRAS Mutations In Colorectal Cancer
Onvansertib targets the major KRAS mutations associated with mCRC
Onvansertib is the only PLK1 inhibitor and targeted therapy in clinical development that has demonstrated activity against aggressive and difficult-to-drug KRAS mutations in metastatic colorectal cancer.
Tumor cells harboring KRAS mutations are more vulnerable to onvansertib
Colorectal cancer tumor cells harboring a KRAS mutation are more vulnerable to cell death with PLK1 inhibition (onvansertib). KRAS-mutated cells are more sensitive to onvansertib than KRAS wild-type cells.
Onvansertib is synergistic in combination with 5-FU and irinotecan (FOLFIRI)
The combinations have demonstrated significantly greater tumor growth inhibition than either drug alone.
Why onvansertib is a promising new treatment option for KRAS-mutated mCRC: Targeting the once ‘undruggable’ KRAS mutations
Approximately 50% of mCRC is associated with the difficult-to-treat KRAS mutation which is believed to drive aggressive tumor growth and resistance to currently available treatment. Despite decades of attempts, until recently there had not been any therapeutic options that specifically and effectively target KRAS mutations.
Patient Jorge Rivera’s Journey
Onvansertib in Combination with FOLFIRI/Avastin® is Demonstrating Safety and Efficacy in KRAS-Mutated Metastatic Colorectal Cancer
Phase 1b/2 multi-center, open-label clinical trial NCT03829410
“So far everything we hoped for has happened - no toxicity and signs of efficacy. We are very optimistic because we are seeing the anti-tumor effects and opening the opportunity for a new treatment designed to attack KRAS-mutant tumors that acts synergistically with standard-of-care chemotherapy”
Dr. Heinz-Josef Lenz, Principal Investigator, USC Norris Comprehensive Cancer Center
Compelling Preliminary Efficacy Data
- 10 of 11 (91%) patients had clinical benefit:
- 5 (45%) patients achieved a partial response (PR)
- 4 patients had a confirmed PR (≥ 30% tumor shrinkage) with 1 patient going on to curative surgery
- 1 patient with an initial PR went off study prior to confirmatory scan due to non-treatment related event
Responses Appear Durable:
8 (73%) patients had durable responses of >6 months (range 6 to >12 months); 4 patients remain on treatment; median PFS has not yet been reached
Only 1 patient progressed in <6 months while on treatment
Monitoring KRAS mutations in plasma ctDNA may enable rapid predictions of therapeutic response
- KRAS mutant allelic frequency (MAF) was measured by digital droplet PCR (ddPCR) at baseline and at the end of Cycle 1
- 9 of 11 patients had a KRAS variant detected by ddPCR at baseline*
- All patients showed a decrease in KRAS MAF after the 1st cycle of treatment
The greatest changes in KRAS were observed in patients achieving a PR (ranging from -78% to -100%)
The patient with disease progression had only a 55% decrease in KRAS mutant allelic frequency
