Phase 1 Study of Safety and PK With A Combination of Omeprazole and Trimetazidine for Fatty Acid Oxidation Inhibition in Patients With Advanced Solid Tumors.
9 affiliations
- 1Center for Clinical Trials, National Cancer Center, Goyang, Republic of Korea.
- 2Research Institute, National Cancer Center, Goyang, Republic of Korea.
- 3Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Republic of Korea.
- 4Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Republic of Korea.
- 5Center for Breast Cancer, National Cancer Center, Goyang, Republic of Korea.
- 6New Cancer Cure-Bio Co, Goyang, Republic of Korea.
- 7Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
- 8Clinical Trials Center, Seoul National University Hospital, Seoul, Republic of Korea.
- 9Department of Convergence Medicine, Department of Digital Medicine, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Abstract
Fatty acid oxidation (FAO) is a metabolic vulnerability in cancer cells, making pharmacologic FAO inhibition a promising therapeutic strategy. This Phase I, open-label, 3 + 3 dose-escalation study evaluated the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of two oral FAO inhibitors-omeprazole (KN510), a carnitine-acylcarnitine translocase inhibitor, and trimetazidine (KN713), an acetyl-CoA acyltransferase inhibitor-given once daily in combination to patients with advanced solid tumors. Twelve patients were enrolled across four dose cohorts (omeprazole and trimetazidine, each 60-120 mg/day). The maximum tolerated dose was not reached; the recommended Phase 2 dose was set at 120 mg once daily for each agent. Treatment was generally well tolerated, with most adverse events Grade 1-2; the most common were flu-like symptoms (25.0%), constipation (16.7%), nausea (16.7%), and dizziness (16.7%). Omeprazole showed time-dependent pharmacokinetics consistent with auto-inhibition of its own metabolism, whereas trimetazidine showed dose-proportional pharmacokinetics across the studied range. The best response was stable disease in five patients (disease control rate 41.7%). Median progression-free survival was 1.66 months (95% CI, 1.18-3.55) and median overall survival was 9.13 months (95% CI, 3.29-not reached). Dual pharmacologic FAO inhibition with oral omeprazole and trimetazidine was feasible and well tolerated, supporting the mechanistic rationale for combination dosing. Disease stabilization observed in this heavily pretreated population warrants further clinical evaluation, particularly in combination with standard chemotherapy regimens. Trial Registration: ClinicalTrials.gov, NCT06012708; registered August 25, 2023.
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BibTeX
@article{choi2026phase,
title = {{Phase 1 Study of Safety and PK With A Combination of Omeprazole and Trimetazidine for Fatty Acid Oxidation Inhibition in Patients With Advanced Solid Tumors.}},
author = {Wonyoung Choi and Jung W Chun and Sung H Sim and Sung-Sik Han and Woo J Lee and Joon H Kang and Hyun Chul Kim and SeungHwan Lee and Jun H Lee and Hyun J Yoo and Soo-Youl Kim and Sang M Woo},
journal = {Clinical and translational science},
year = {2026},
month = oct,
doi = {10.1111/cts.70752},
url = {https://europepmc.org/article/MED/42951875},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Phase 1 Study of Safety and PK With A Combination of Omeprazole and Trimetazidine for Fatty Acid Oxidation Inhibition in Patients With Advanced Solid Tumors.
AU - Wonyoung Choi
AU - Jung W Chun
AU - Sung H Sim
AU - Sung-Sik Han
AU - Woo J Lee
AU - Joon H Kang
AU - Hyun Chul Kim
AU - SeungHwan Lee
AU - Jun H Lee
AU - Hyun J Yoo
AU - Soo-Youl Kim
AU - Sang M Woo
PY - 2026
DA - 2026/10/28
JO - Clinical and translational science
DO - 10.1111/cts.70752
UR - https://europepmc.org/article/MED/42951875
AB - Fatty acid oxidation (FAO) is a metabolic vulnerability in cancer cells, making pharmacologic FAO inhibition a promising therapeutic strategy. This Phase I, open-label, 3 + 3 dose-escalation study evaluated the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of two oral FAO inhibitors-omeprazole (KN510), a carnitine-acylcarnitine translocase inhibitor, and trimetazidine (KN713), an acetyl-CoA acyltransferase inhibitor-given once daily in combination to patients with advanced solid tumors. Twelve patients were enrolled across four dose cohorts (omeprazole and trimetazidine, each 60-120 mg/day). The maximum tolerated dose was not reached; the recommended Phase 2 dose was set at 120 mg once daily for each agent. Treatment was generally well tolerated, with most adverse events Grade 1-2; the most common were flu-like symptoms (25.0%), constipation (16.7%), nausea (16.7%), and dizziness (16.7%). Omeprazole showed time-dependent pharmacokinetics consistent with auto-inhibition of its own metabolism, whereas trimetazidine showed dose-proportional pharmacokinetics across the studied range. The best response was stable disease in five patients (disease control rate 41.7%). Median progression-free survival was 1.66 months (95% CI, 1.18-3.55) and median overall survival was 9.13 months (95% CI, 3.29-not reached). Dual pharmacologic FAO inhibition with oral omeprazole and trimetazidine was feasible and well tolerated, supporting the mechanistic rationale for combination dosing. Disease stabilization observed in this heavily pretreated population warrants further clinical evaluation, particularly in combination with standard chemotherapy regimens. Trial Registration: ClinicalTrials.gov, NCT06012708; registered August 25, 2023.
SN - 1752-8054
SN - 1752-8062
ER -