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Kura Oncology (Nasdaq: KURA) showcased promising preliminary clinical and preclinical results at ESMO 2025, highlighting the potential of its farnesyl transferase inhibitors (FTIs), darlifarnib (KO-2806) and tipifarnib, both as monotherapies and in combination regimens. The data signal a potential shift in targeted cancer therapies, particularly in addressing resistance mechanisms.
Key findings include: Darlifarnib monotherapy demonstrating a tolerable dosing range of 3–10 mg/day, exhibiting on-target activity in HRAS-mutant tumors. Combination therapy of darlifarnib and cabozantinib yielded an objective response rate (ORR) of 33–50% and a disease control rate (DCR) of 80–100% in patients with clear cell renal cell carcinoma (RCC). Impressively, the combination of tipifarnib and alpelisib produced a 47% ORR when using tipifarnib at 1200 mg and alpelisib at 250 mg in heavily pretreated PIK3CA-altered head and neck squamous cell carcinoma (HNSCC). An investor event was held on October 18, 2025.
Positive
Darlifarnib+cabozantinib ORR 33%–50% in clear cell RCC
Darlifarnib+cabozantinib DCR 80%–100% in clear cell RCC
Tipifarnib+alpelisib ORR 47% at 1200 mg/250 mg in PIK3CA‑altered HNSCC
Darlifarnib monotherapy tolerable at 3–10 mg/day with on‑target activity in HRAS‑mutant tumors
Negative
Alpelisib monotherapy ORR 0% (BOR: SD) in the tested HNSCC population
Tipifarnib monotherapy not expected to provide clinical benefit in this population
Key combination data are preliminary from dose‑escalation and remain subject to ongoing study
Insights
Kura reports promising early combo efficacy for FTIs, notably high response rates in RCC and HNSCC cohorts, supporting further development.
Kura Oncology presented preliminary clinical and preclinical data for its farnesyl transferase inhibitors darlifarnib and tipifarnib showing activity as monotherapy in HRAS‑mutant tumors and as combination partners with TKIs, PI3Kα inhibitors and KRAS inhibitors. The company reports an objective response rate (ORR) of 50% and disease control rate (DCR) of 80% in a renal cell carcinoma cohort treated with darlifarnib plus cabozantinib in a dose‑escalation trial, plus an ORR of 47% for tipifarnib plus alpelisib in heavily pretreated PIK3CA‑altered HNSCC at the specified dose.
The business mechanism is clear in the disclosed data: FTIs are presented as agents that block farnesylation‑dependent pathways, including hyperactivated mTORC1 signaling in tumor endothelial and squamous tumor cells, which the company links to improved activity when combined with targeted agents. Safety is described as manageable across reported dose ranges, including at the full label dose of cabozantinib. Key dependencies and risks are explicit: the findings are preliminary and arise from early phase (dose‑escalation and Phase 1) cohorts, with ongoing dose‑escalation and a planned Phase 1b dose‑expansion noted; durability, broader reproducibility, and formal dose selection remain unresolved in the disclosed material.
Concrete near‑term items to watch are the completion and readout of the ongoing dose‑escalation, the planned Phase 1b dose‑expansion for darlifarnib plus cabozantinib, and additional cohort-level data for HRAS‑mutant monotherapy and darlifarnib+PI3Kα combinations; these are relevant over the next 6–18 months given the ongoing early‑phase work and the virtual investor event on October 18, 2025.
10/18/2025 – 03:23 AM
FTI mechanism addresses innate and adaptive resistance pathways common to targeted oncology therapies
Early clinical and preclinical data support darlifarnib’s potential to enhance clinical benefit of PI3Kα-, KRAS- and tyrosine kinase inhibitors
50% objective response rate and 80% disease control rate in renal cell carcinoma (RCC) cohort of darlifarnib plus cabozantinib in ongoing dose-escalation clinical trial
Kura Oncology recently presented findings at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, Germany. The data, highlighted in a press release, focuses on their Farnesyl Transferase Inhibitor (FTI) programs, darlifarnib (KO-2806) and tipifarnib, and the potential to improve the clinical application of targeted therapies for cancer by addressing resistance mechanisms.
Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology, emphasized the company’s pioneering role in combining FTIs with tyrosine kinase inhibitors (TKIs), PI3Kα inhibitors, and KRAS inhibitors. The goal is to combat mechanisms of innate and adaptive resistance and extend the benefits of single-agent targeted therapies.
#####Key Clinical Data
* **Darlifarnib Monotherapy (FIT-001 Phase 1 Trial):** In patients with advanced solid tumors, HRAS-mutant tumors showed sensitivity to FTIs. The drug exhibited a manageable safety profile at doses from 3 to 10 mg per day, with encouraging antitumor activity. These results support a broader evaluation of KO-2806 in diverse tumor types.
* **Darlifarnib + Cabozantinib in Renal Cell Carcinoma (FIT-001 Phase 1 Trial):** The FTI mechanism blocks hyperactivated mTORC1 signaling in tumor endothelial cells. Preliminary results showed a manageable safety profile in RCC patients, even at the full label dose of cabozantinib. Antitumor activity was observed across all doses in RCC, including in patients previously exposed to cabozantinib, with an ORR of 33%-50% and a DCR of 80%-100% in clear cell RCC. Data from dose-escalation studies will inform the planned Phase 1b dose-expansion trial.
* **Tipifarnib + Alpelisib in *PIK3CA*-altered Head and Neck Squamous Cell Carcinoma (KURRENT-HN Phase 1 Trial):** The FTI mechanism blocks hyperactivated mTORC1 signaling in squamous tumor cells. The combination showed robust antitumor activity in heavily pretreated patients with relapsed or metastatic HNSCC with *PIK3CA* alterations. An ORR of 47% was observed at a daily dose of tipifarnib 1200 mg + alpelisib 250 mg. Alpelisib monotherapy offers limited clinical benefit in this population (ORR: 0%; BOR: SD), and tipifarnib monotherapy is not expected to improve outcomes.
#####Expert Commentary
Glenn Hanna, M.D., Director, Center for Cancer Therapeutic Innovation, at Dana-Farber Cancer Institute, stated that these results emphasize the ability of FTIs to enhance the clinical performance of PI3Kα inhibitors in molecularly selected patients. The activity of darlifarnib in HRAS-mutant solid tumors, which are typically challenging to manage, is particularly encouraging. He also highlighted that combining tipifarnib and alpelisib produced robust antitumor activity in HNSCC patients harboring PIK3CA alterations, where monotherapy alpelisib offers only modest clinical benefit. According to Kura Oncology, the combination sets the stage for partnering darlifarnib with PI3Kα inhibitors.
#####Moving Forward
Kura Oncology is forging ahead with dose-escalation studies and a Phase 1b dose-expansion trial to pinpoint the optimal biologically active dose for the darlifarnib + cabozantinib combination.
#####Financial Implications
While the company acknowledges the need for further research to validate these early findings, the demonstrated capacity of FTIs to improve targeted therapies underscores Kura’s position as a key player in the precision medicine landscape. The advancements could potentially lead to higher valuations and partnership opportunities. Investors are keeping a close eye on ongoing trials, with a focus on the completion and readout of the dose-escalation studies and the Phase 1b dose-expansion for darlifarnib plus cabozantinib. Positive results could trigger significant market response.
FAQ
What preliminary results did KURA report at ESMO 2025 for darlifarnib (KURA)?
Kura reported darlifarnib monotherapy tolerable at 3–10 mg/day with on‑target activity in HRAS‑mutant tumors and combination activity with cabozantinib in RCC.
What response rates did KURA report for darlifarnib plus cabozantinib in RCC (KURA)?
The company reported an ORR of 33%–50% and a DCR of 80%–100% in clear cell RCC, with a 50% ORR noted in an RCC cohort.
What was the clinical activity of tipifarnib plus alpelisib in PIK3CA‑altered HNSCC (KURA)?
Tipifarnib 1200 mg plus alpelisib 250 mg produced an ORR of 47% in heavily pretreated, PIK3CA‑altered HNSCC patients.
Did KURA announce any safety or tolerability findings for the FTI combinations at ESMO 2025 (KURA)?
Kura reported a manageable safety profile for darlifarnib and tipifarnib combinations across multiple doses, including at full label dose of cabozantinib in RCC.
Will KURA provide more detail on these ESMO 2025 data and when (KURA)?
Presentations are available on the company website and a virtual investor webcast and replay were scheduled for October 18, 2025.
What are the near‑term development plans KURA disclosed for darlifarnib combinations (KURA)?
Kura is continuing dose‑escalation studies and plans a Phase 1b dose‑expansion to assess the optimal biologically active dose for the darlifarnib+cabozantinib combination.
