Kura Oncology (NASDAQ:KURA) presented updated results from its Phase 1 FIT-001 trial evaluating darlifarnib in combination with cabozantinib for locally advanced or metastatic renal cell carcinoma (RCC) that had progressed after prior treatment, including immunotherapy.
The company’s investor call followed a presentation at the KCRS symposium in Boston. The updated analysis focused on cabozantinib-naive patients with clear cell RCC, while safety findings included all RCC patients enrolled in the study.
Response and Progression-Free Survival Results
Among the overall study population, 67% had previously received an immunotherapy-plus-TKI regimen, 38% had prior cabozantinib exposure and 17% had received a prior HIF-2 alpha inhibitor, according to the presentation.
In cabozantinib-naive clear cell RCC patients, objective response rates across dose cohorts ranged from 33% to 50%. The cohort receiving 5 milligrams of darlifarnib plus 60 milligrams of cabozantinib reported a 50% objective response rate. Disease control rates ranged from 83% to 100% across the evaluated groups.
The company reported a median progression-free survival of 13 months in cabozantinib-naive clear cell RCC patients, with a six-month progression-free survival probability of 74% and a nine-month probability of 60%. More than half of patients remained on treatment at the data cutoff, Ayanambakkam said.
Earlier data in cabozantinib-exposed patients showed a 44% objective response rate and a 94% disease control rate, according to Kura. Troy Wilson, Kura’s president and chief executive officer, said the results supported the company’s view that darlifarnib may enhance the activity of targeted therapies, including TKIs.
Safety Profile and Neutropenia Management
The combination was described as manageable, with adverse events generally consistent with those associated with cabozantinib and the TKI class, including diarrhea, nausea, stomatitis and hand-foot syndrome. Ayanambakkam said these events were predominantly below Grade 3.
Treatment-emergent adverse events of any grade were reported in 90% of patients in association with darlifarnib and 96% in association with cabozantinib. Grade 3 or higher treatment-emergent adverse events were reported in 58% and 57% of patients, respectively, while serious treatment-emergent adverse events were reported in fewer than 20% of patients in each group.
Neutropenia was the most notable treatment-related safety finding, occurring at any grade in 47% of patients and at Grade 3 in 38% of patients. During the dose-limiting toxicity period, growth-factor support was not permitted. In the ongoing expansion phase, granulocyte colony-stimulating factor support is allowed to help manage neutropenia and potentially avoid darlifarnib dose modifications.
Ayanambakkam said neutropenia appeared early in treatment rather than as a cumulative toxicity. He added that dose interruptions, rechallenge and, when appropriate, growth-factor support had enabled continued treatment for some patients.
Ongoing Expansion Study and Development Plans
The Phase 1B expansion portion of FIT-001 is enrolling patients in a randomized 1:1:1 design. The study is comparing darlifarnib at 5 mg plus cabozantinib at 60 mg, darlifarnib at 8 mg plus cabozantinib at 60 mg, and cabozantinib monotherapy at 60 mg. Patients initially assigned to cabozantinib alone may subsequently enroll in a combination cohort after progression.
Mollie Leoni, Kura’s chief medical officer, said the dose-optimization study is intended to support future registrational trials. Kura expects to share data from the Phase 1B trial in the second half of 2027.
Leoni said the company sees a potential initial registration opportunity in second- or third-line advanced RCC, while a planned platform-trial approach could evaluate darlifarnib in broader and potentially earlier-line combinations. Management has not yet finalized the design of a registration-enabling trial.
Wilson said Kura believes darlifarnib could potentially be combined with multiple TKIs rather than only cabozantinib. He also cited development plans involving daraxonrasib in second-line pancreatic ductal adenocarcinoma. The company said it had $580 million in cash and expected $180 million in collaboration payments from Kyowa Kirin in the relatively near term.
About Kura Oncology (NASDAQ:KURA)
Kura Oncology, Inc (NASDAQ: KURA) is a clinical-stage biopharmaceutical company focused on the discovery and development of targeted oncology therapies. Headquartered in La Jolla, California, the company leverages expertise in molecular biology and precision medicine to identify key drivers of cancer growth and design small-molecule inhibitors that block those pathways. Kura’s research platform integrates genomic insights with medicinal chemistry to advance candidates against well-validated targets in solid tumors and hematologic malignancies.
The company’s lead clinical candidate, tipifarnib, is a farnesyltransferase inhibitor being evaluated for the treatment of HRAS-mutant head and neck squamous cell carcinoma and various non-small cell lung cancers.
