Jiujie Cui1,2,3, Haiyan Yang1,2,3, Jue Liu4, Donghui Chen3, Jiong Hu1,2,3, Haiyan Zhang3, Yu Wang1,2,3, Ting Han1,2,3, Tiebo Mao1,2, Feng Jiao1,2,3, Ewelina Biskup5, Yaotian Pan6, Min Liu7, Liwei Wang8,9,10. 1. Department of Medical Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 2. State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 3. Department of Oncology, First People's Hospital, Shanghai Jiaotong University, Shanghai, China. 4. Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China. 5. College of Fundamental Medicine, Shanghai University of Medicine and Health Sciences, Shanghai, China. 6. Institute of Psychology Chinese Academy of Sciences, Beijing, China. panyt@psych.ac.cn. 7. Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China. liumin@bjmu.edu.cn. 8. Department of Medical Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. liweiwang@shsmu.edu.cn. 9. State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. liweiwang@shsmu.edu.cn. 10. Department of Oncology, First People's Hospital, Shanghai Jiaotong University, Shanghai, China. liweiwang@shsmu.edu.cn.
Abstract
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease that lack of effective therapeutic drugs. K-001 is an oral antitumor drug made from active ingredients of marine microorganisms. The current study aimed to evaluate safety and antitumor activity of K-001 in patients with advanced PDAC. METHODS: In this phase I, open-label trial, patients with advanced PDAC were recruited to a dose-escalation study in a standard 3 + 3 design. K-001 was administered twice daily in four-week cycles, and dose escalation from 1350 mg to 2160 mg was evaluated twice daily. Physical examination and laboratory tests were done at screening and then weekly. The safety, dose-limiting toxicity (DLT), and maximum tolerated dose (MTD) of K-001 were assessed while tumor response was estimated by Response Evaluation Criteria in Solid Tumor (RECIST). RESULTS: Eighteen patients with advanced PDAC were screened, and twelve eligible patients were analyzed in the study. No DLT was observed. Totally, 47 adverse events (AEs) presented, and 14 drug-related AEs were reported in 7 patients, including 8 grade 1 events (57.1%) and 6 grade 2 events (42.9%). There was no grade 3 or 4 drug-related AE. In these 14 drug-related AEs, the most frequent ones were dyspepsia (21.4%), followed by flatulence, constipation, and hemorrhoid bleeding (above 10% of each). Among all 12 patients, 10 patients (83.3%) maintained stable disease (SD), and 2 patients (16.7%) had progressive disease (PD). The objective response rate (ORR) was 0% and the disease control rate (DCR) was 83.3%. CONCLUSIONS: K-001 manifests satisfactory safety and tolerability, as well as meaningful antitumor activity in advanced PDAC patients. Further evaluation of K-001 in phase II/III appears warranted. TRIAL REGISTRATION: NCT02720666 . Registered 28 Match 2016 - Retrospectively registered.
BACKGROUND:Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease that lack of effective therapeutic drugs. K-001 is an oral antitumor drug made from active ingredients of marine microorganisms. The current study aimed to evaluate safety and antitumor activity of K-001 in patients with advanced PDAC. METHODS: In this phase I, open-label trial, patients with advanced PDAC were recruited to a dose-escalation study in a standard 3 + 3 design. K-001 was administered twice daily in four-week cycles, and dose escalation from 1350 mg to 2160 mg was evaluated twice daily. Physical examination and laboratory tests were done at screening and then weekly. The safety, dose-limiting toxicity (DLT), and maximum tolerated dose (MTD) of K-001 were assessed while tumor response was estimated by Response Evaluation Criteria in Solid Tumor (RECIST). RESULTS: Eighteen patients with advanced PDAC were screened, and twelve eligible patients were analyzed in the study. No DLT was observed. Totally, 47 adverse events (AEs) presented, and 14 drug-related AEs were reported in 7 patients, including 8 grade 1 events (57.1%) and 6 grade 2 events (42.9%). There was no grade 3 or 4 drug-related AE. In these 14 drug-related AEs, the most frequent ones were dyspepsia (21.4%), followed by flatulence, constipation, and hemorrhoid bleeding (above 10% of each). Among all 12 patients, 10 patients (83.3%) maintained stable disease (SD), and 2 patients (16.7%) had progressive disease (PD). The objective response rate (ORR) was 0% and the disease control rate (DCR) was 83.3%. CONCLUSIONS:K-001 manifests satisfactory safety and tolerability, as well as meaningful antitumor activity in advanced PDACpatients. Further evaluation of K-001 in phase II/III appears warranted. TRIAL REGISTRATION: NCT02720666 . Registered 28 Match 2016 - Retrospectively registered.
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