Kura Oncology (KURA) Study update summary

Study Background and Rationale

• FIT-001 is a phase I study evaluating darlifarnib plus cabozantinib in advanced/metastatic RCC, including both clear cell and non-clear cell subtypes, with a focus on heavily pretreated and immunotherapy-refractory patients.

• Darlifarnib is a next-generation farnesyl transferase inhibitor that selectively blocks mTORC1 via Rheb inhibition, aiming to enhance targeted therapy efficacy.

• The combination is designed to provide dual pathway blockade, potentially overcoming resistance and improving outcomes compared to monotherapy.

Patient Population and Study Design

• 72 RCC patients enrolled as of May 8, 2026, median age 67, 80–81% with clear cell RCC; most had prior IO and/or TKI exposure, with 38% having prior cabozantinib.

• Dose escalation and expansion included multiple darlifarnib and cabozantinib dose levels; efficacy focus on cabozantinib-naive clear cell RCC.

• Phase I-B expansion randomizes patients to darlifarnib 5 mg + cabo 60 mg, darlifarnib 8 mg + cabo 60 mg, or cabo 60 mg monotherapy, with crossover allowed.

• Median follow-up was 8.8 months (range 0.9–20.6); 27 patients remained on treatment at data cutoff.

• The global Phase 1b study is ongoing in the U.S. and E.U., enrolling cabozantinib-naive, refractory ccRCC patients.

Efficacy and Clinical Activity

• In cabozantinib-naive ccRCC, objective response rates ranged from 33% to 50% across dose levels; the 5 mg darlifarnib + 60 mg cabo cohort achieved a 50% ORR.

• Disease control rates reached up to 100% in some cohorts; clinical benefit rate exceeded 70% in the 5 mg cohort.

• Median progression-free survival was 13 months, with 74% six-month and 60% nine-month PFS probabilities.

• Durable responses observed, with over half of patients remaining on treatment at data cutoff; some partial responses maintained for up to 48 weeks.

• The combination outperformed historical cabozantinib monotherapy benchmarks in 2L/3L RCC.