On September 28, 2023 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported preclinical data supporting the development of its next-generation farnesyl transferase inhibitor (FTI) KO-2806 in combination with KRASG12C inhibitors to drive tumor regressions and durable responses in KRASG12C-mutant non-small cell lung cancer (NSCLC) (Press release, Kura Oncology, SEP 28, 2023, View Source [SID1234635501]).
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The new findings are being presented in an oral session today at the 5th RAS-Targeted Drug Development Summit in Boston. A copy of the presentation, entitled "Farnesyl Transferase Inhibitors – Evolution from Targeting HRAS to Overcoming Adaptive Resistance to Targeted Therapies," is available in the Posters and Presentations section on Kura’s website.
KRASG12C inhibitors have previously been shown to activate RTK signaling, leading to ERK-RSK and/or mTOR-S6 pathway reactivation. The Company’s new preclinical data show that co-treatment of preclinical models of KRASG12C-mutant NSCLC with KO-2806 and adagrasib deepens signaling inhibition at multiple nodes, including the MAPK and mTOR pathways, while decreasing cell proliferation. In both cell-derived (CDX) and patient-derived (PDX) xenograft models originating from NSCLC tumors, the combination of KO-2806 with adagrasib induced tumor regressions. In addition, the CDX and PDX models demonstrated enhanced duration and depth of antitumor response compared to adagrasib as a single-agent therapy.
"Despite advances with KRAS-targeted therapies, a significant unmet need remains for patients with KRASG12C-mutant NSCLC as acquired resistance occurs early and often," said Francis Burrows, Ph.D., Senior Vice President, Translational Research. "We are highly encouraged by these first preclinical data for KO-2806, which demonstrate the potential for FTIs as a mechanism-based combination agent to enhance antitumor activity of targeted therapies, such as KRASG12C inhibitors."
Kura is on track to dose the first patient in its Phase 1 dose-escalation trial of KO-2806 (FIT-001) in the second half of 2023. Concurrent with the monotherapy dose escalation, the Company plans to evaluate KO-2806 in dose-escalation combination cohorts with other targeted therapies in advanced solid tumors, including clear cell renal cell carcinoma (ccRCC) and KRASG12C NSCLC.