Abstract
2604P Farnesyltransferase inhibitor (FTI) KO-2806 in combination with cabozantinib (cabo) in renal cell carcinoma (RCC): Preliminary results from FIT-001 phase I trial
Annals of oncology, Vol.36(Suppl 2), pp.S1397-S1398
09/2025
DOI: 10.1016/j.annonc.2025.08.3220
Abstract
Background
Limitations in VEGFR-targeted therapy for RCC highlight the need for combination (combo) strategies. Preclinical studies have shown KO-2806, a next-generation FTI, can enhance the antiangiogenic/antitumor activity of cabo, supporting potential for this combo to improve clinical activity in clear cell (cc) and non-cc (ncc) RCC.
Methods
FIT-001 (NCT06026410) is an ongoing, multicenter Ph1a/b study of KO-2806 alone and in combo in patients (pts) with advanced solid tumors. KO-2806 3, 5 or 8 mg D1–7,15–21 + cabo 40 mg in 28-day cycles was evaluated in advanced RCC. Cc: ≥1 prior systemic immunotherapy (IO) based treatment (tx); ncc: tx naïve/any prior systemic tx. Primary objectives: safety/tolerability; secondary objectives: preliminary antitumor activity, pharmacokinetic analyses. Here we present preliminary results of KO-2806 + cabo combo.
Results
As of 21 Mar 2025, 27 pts (21 cc, 6 ncc) received KO-2806 3, 5 or 8 mg + cabo. Median age: 65y; 70% male. Prior IO/TKI: 8 pts (30%) IO only, 18 pts (67%) IO + TKI, 1 pt (4%) other; 13 pts (48%) prior cabo. Most common (≥20%) any Gr KO-2806-related AEs (TRAEs) were neutropenia (33%); fatigue and nausea (26% each); decreased appetite, anemia, diarrhea, and vomiting (22% each). Gr≥3 KO-2806-related neutropenia occurred in 3 (30%) and 5 (56%) pts with KO-2806 5 and 8 mg + cabo, respectively; no KO-2806-related neutropenia occurred with KO-2806 3 mg + cabo. Most common (≥20%) any Gr cabo TRAEs were nausea and fatigue (30% each); decreased appetite (26%); diarrhea, dysgeusia, and vomiting (22% each). One pt discontinued per investigator due to Gr2 neutropenia attributed to KO-2806. Of 20 response-evaluable pts (≥1 postbaseline scan), 5 (25%) receiving KO-2806 + cabo achieved confirmed partial response (n=4 cc; n=1 ncc); 16 (59%) stable disease (SD). Among responders, 2 of 5 were cabo-resistant (best prior response: SD; 1 with 4 prior lines of tx) and 3 of 5 were cabo-naïve. KO-2806 + cabo 60 mg is being assessed. Updated data to be presented.
Conclusions
KO-2806 + cabo combo demonstrates clinical activity in cabo-naïve and -resistant RCC with a manageable safety profile, supporting further investigation of KO-2806 combos in RCC and other advanced cancers.
Details
- Title: Subtitle
- 2604P Farnesyltransferase inhibitor (FTI) KO-2806 in combination with cabozantinib (cabo) in renal cell carcinoma (RCC): Preliminary results from FIT-001 phase I trial
- Creators
- A. AyanambakkamL.S. RosenB. GarmezyM. PelsterG.J. HannaJ. ThomasM.R. PatelD. LauxN. BendrisS. DaleA. SaundersJ. KuanB. BalsaraJ. SerajA. Singer
- Resource Type
- Abstract
- Publication Details
- Annals of oncology, Vol.36(Suppl 2), pp.S1397-S1398
- DOI
- 10.1016/j.annonc.2025.08.3220
- ISSN
- 0923-7534
- eISSN
- 1569-8041
- Publisher
- Elsevier; AMSTERDAM
- Grant note
- Kura Oncology, Inc.
Funding: Kura Oncology, Inc.
- Language
- English
- Date published
- 09/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9985027358002771
Metrics
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