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.
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.
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.
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”
Efficacy for 8 evaluable patients treated with onvansertib 12 mg/m2 and 15 mg/m2:
- 7 of 8 (88%) patients had clinical benefit: 3 partial response (PR) and 4 stable disease (SD)
- 1 patient proceeded to successful curative surgery
- Responses appear durable:
- Median PFS of 6.5 months to-date
- 6 patients remain on treatment
Changes in Plasma KRAS Mutant are Predictive of Tumor Regression
- 6 of the 8 patients evaluable for efficacy showed tumor regression at 8 weeks
- Decreases in plasma KRAS mutation level has been demonstrated to be an early marker for therapeutic response
- 7 of the 8 patients had a KRAS mutation detected by ctDNA analysis at baseline (ddPCR and NGS)
- Changes in KRAS mutant during cycle 1 of treatment were highly predictive of tumor regression:
- 5 patients had a decrease in KRAS mutant to non-detectable level in cycle 1 (28 days) and subsequent tumor regression at 8 weeks (cycle 3 day 1)
- 2 patients had detectable KRAS mutant at end of cycle 1 and showed tumor growth at cycle 3 day 1