On April 17, 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 potential use of farnesyl transferase inhibitors (FTIs) to treat various types of solid tumors in combination with targeted therapies, including KRASG12C inhibitors and anti-angiogenic tyrosine kinase inhibitors (TKIs) (Press release, Kura Oncology, APR 17, 2023, View Source [SID1234630163]). These data were featured in two poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting on Sunday, April 16 in Orlando. Copies of the posters are available on Kura’s website at www.kuraoncology.com/pipeline/publications.
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New preclinical data in the poster titled, ‘Tipifarnib synergizes with a TKI in clear cell renal cell carcinoma models,’ demonstrates the synergistic activity of tipifarnib and axitinib, a TKI approved to treat advanced renal cell carcinoma (RCC), in cell- and patient-derived RCC xenograft models. These data support the potential to administer an FTI in combination with a TKI for the treatment of RCC, and studies are ongoing to further evaluate the mechanistic basis of the synergy observed with the combination.
In addition, new findings were presented in the poster titled, ‘Combination of tipifarnib with KRASG12C inhibitors to prevent adaptive resistance,’ evaluating the effects of tipifarnib in combination with adagrasib and sotorasib in cell line and xenograft models of KRASG12C mutant non-small cell lung cancer (NSCLC). These data reveal that the addition of tipifarnib leads to significant tumor regression in xenograft models and suppresses mTOR signaling reactivation relative to treatment with the KRASG12C inhibitors alone. These results support further preclinical studies to determine the mechanism of action for the combination.
"Although targeted therapies have demonstrated meaningful clinical activity, including objective responses, across a range of solid tumors, over time adaptive resistance almost invariably emerges, limiting the ability of the targeted therapies to drive sustained clinical benefit. Yesterday, we presented encouraging preclinical data that highlight the potential for FTIs to prevent or delay emergence of resistance to certain classes of targeted therapies," said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. "We believe these promising preclinical data strongly support our rationale to combine KO-2806 with KRASG12C mutant inhibitors and TKIs in NSCLC and RCC, respectively."
In parallel to the clinical evaluation of tipifarnib, the Company is advancing KO-2806, a potent inhibitor of farnesyl transferase that was designed to improve upon potency, pharmacokinetic and physicochemical properties of earlier FTI drug candidates. The Company expects to initiate the Phase 1 first-in-human study (FIT-001) later this year to assess safety, tolerability and preliminary antitumor activity of KO-2806 as a monotherapy and in combination with other targeted therapies in adult patients with advanced solid tumors. Following completion of the dose escalation as a monotherapy, Kura plans to evaluate KO-2806 in dose escalation combination cohorts in advanced solid tumors.