Abstract CT069: A phase I study of the first-in-class anti-fatty acid oxidation agent, KN510713, in patients with advanced solid cancers

Abstract Purpose: We discovered that cancer cells rely heavily on fatty acid oxidation (FAO) for ATP production, unlike normal cells. This led to the development of the FAO inhibitor KN510713. This study explored the effects of KN510713 on mitochondria and evaluated its safety, tolerability, and pharmacokinetics in patients with relapsed or refractory solid tumors, mainly focusing on advanced pancreatic cancer. Experimental Design: Patients were enrolled in escalating dose cohorts to receive the combination of KN510 and KN713 for 4 weeks per cycle in a 3 + 3 design. Patients continued treatment until disease progression. Adverse effects (AEs) and dose-limiting toxicities (DLTs) were monitored. Pharmacokinetics were assessed after the 1st and 21st doses. Results: Among the 12 subjects who received the investigational product at least once, 39 AEs occurred in 11 subjects. Of these, 16 AEs were assessed to have a relationship with the KN510713. Among the AEs that occurred in the subjects, except for 2 severe cases (Hypersensitivity, Constipation), all others were mild to moderate, and no subjects dropped out of the clinical trial due to the AEs. There was 1 serious adverse event (Constipation), and the most common AEs were Influenza-like illness with 6 events in 5 subjects, followed by Diarrhoea with 4 events in 3 subjects. Since no DLTs occurred, the highest tested dose of KN510 120 mg/day + KN713 120 mg/day was well-tolerated. Pharmacokinetic analysis showed dose-proportional increases in plasma concentrations of KN510 and KN713 across all cohorts with proper pharmacokinetic profiles allowing for once-daily dosing. No significant drug-drug interactions were observed between KN510 and KN713. Of the 12 evaluable, heavily pretreated patients, 4 achieved stable disease, and one patient with pancreatic cancer achieved prolonged stabilization for 6 months. Conclusion: Our findings indicate that KN510713 was well-tolerated up to the highest dose tested, with no DLTs observed.(ClinicalTrials.gov identifier: NCT06012708) Citation Format: Sang Myung Woo, Wonyoung Choi, Jung Won Chun, Sung Hoon Sim, Ho Lee, Woo Jin Lee, Joon Hee Kang, Hyun Chul Kim, Sungyeun Bae, SeungHwan Lee, Soo-Youl Kim. A phase I study of the first-in-class anti-fatty acid oxidation agent, KN510713, in patients with advanced solid cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT069.