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.

  • 50% of patients with mCRC have a KRAS mutation
  • Prognosis is poor with a five-year survival rate of 10%
  • Other drugs currently in development do not address the most prevalent KRAS mutations in mCRC
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
  • 12 of 14 (86%) patients had clinical benefit:
    • 5 (36%) 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:
  • 18 patients were treated in Phase 1b (6 patients at each dose level); 2 patients did not complete cycle 1 (1 at 12 mg/m2 and 1 at 18 mg/m2); 2 patients at 15 mg/m2 completed cycle 1 of treatment, but have not reached their first 8-week scan
  • 14 patients are currently evaluable for efficacy*:
    • 12 of 14 (86%) patients achieved a clinical benefit (SD + PR)
    • 5 (36%) patients have achieved a partial response (PR); 4 patients had a confirmed PR; 1 patient went on to have curative surgery; 1 patient with non-confirmed PR went off study following PR due to treatment-unrelated AE
    • Time to patients on trial achieving a PR ranges from 2 to 6 months
KRAS Mutant Allelic Frequency (MAF) Biomarker Analyses
  • KRAS MAF was measured by digital droplet PCR (ddPCR) at baseline (Cycle 1 Day 1, pre-dose) and on-treatment (Day 1 of Cycles 2 to 9)
  • 12 of 14 patients had a KRAS mutation detected by ddPCR at baseline (all had a KRAS mutation detected by NGS)
  • Clinical responses were observed across different KRAS mutations, including the 3 most common in CRC (G12D, G12V, G13D)
  • The greatest decreases in KRAS MAF after 1 cycle of treatment were observed in patients achieving a PR
    • All 5 patients with a PR had >75% decrease
    • 4 of the 5 patients with SD had reductions >75%
    • the 2 patients who progressed showed a more modest decrease in KRAS MAF (-55% and -26%)