PMID- 34098895 OWN - NLM STAT- MEDLINE DCOM- 20211018 LR - 20211018 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 21 IP - 1 DP - 2021 Jun 7 TI - A phase I study of the safety and activity of K-001 in patients with advanced pancreatic ductal adenocarcinoma. PG - 672 LID - 10.1186/s12885-021-08375-6 [doi] LID - 672 AB - 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. FAU - Cui, Jiujie AU - Cui J AD - Department of Medical Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. AD - State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. AD - Department of Oncology, First People's Hospital, Shanghai Jiaotong University, Shanghai, China. FAU - Yang, Haiyan AU - Yang H AD - Department of Medical Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. AD - State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. AD - Department of Oncology, First People's Hospital, Shanghai Jiaotong University, Shanghai, China. FAU - Liu, Jue AU - Liu J AD - Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China. FAU - Chen, Donghui AU - Chen D AD - Department of Oncology, First People's Hospital, Shanghai Jiaotong University, Shanghai, China. FAU - Hu, Jiong AU - Hu J AD - Department of Medical Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. AD - State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. AD - Department of Oncology, First People's Hospital, Shanghai Jiaotong University, Shanghai, China. FAU - Zhang, Haiyan AU - Zhang H AD - Department of Oncology, First People's Hospital, Shanghai Jiaotong University, Shanghai, China. FAU - Wang, Yu AU - Wang Y AD - Department of Medical Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. AD - State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. AD - Department of Oncology, First People's Hospital, Shanghai Jiaotong University, Shanghai, China. FAU - Han, Ting AU - Han T AD - Department of Medical Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. AD - State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. AD - Department of Oncology, First People's Hospital, Shanghai Jiaotong University, Shanghai, China. FAU - Mao, Tiebo AU - Mao T AD - Department of Medical Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. AD - State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. FAU - Jiao, Feng AU - Jiao F AD - Department of Medical Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. AD - State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. AD - Department of Oncology, First People's Hospital, Shanghai Jiaotong University, Shanghai, China. FAU - Biskup, Ewelina AU - Biskup E AD - College of Fundamental Medicine, Shanghai University of Medicine and Health Sciences, Shanghai, China. FAU - Pan, Yaotian AU - Pan Y AD - Institute of Psychology Chinese Academy of Sciences, Beijing, China. panyt@psych.ac.cn. FAU - Liu, Min AU - Liu M AD - Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China. liumin@bjmu.edu.cn. FAU - Wang, Liwei AU - Wang L AUID- ORCID: 0000-0002-0031-4363 AD - Department of Medical Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. liweiwang@shsmu.edu.cn. AD - 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. AD - Department of Oncology, First People's Hospital, Shanghai Jiaotong University, Shanghai, China. liweiwang@shsmu.edu.cn. LA - eng SI - ClinicalTrials.gov/NCT02720666 GR - 2018ZX09711001-007-010/Development Center for Medical Science & Technology National Health Commission of the People's Republic of China/ PT - Clinical Trial, Phase I PT - Journal Article DEP - 20210607 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 RN - 0 (Biological Products) RN - 0 (Peptidoglycan) SB - IM MH - Aged MH - Aquatic Organisms/*chemistry MH - Biological Products/administration & dosage/*adverse effects MH - Carcinoma, Pancreatic Ductal/diagnosis/*drug therapy/pathology MH - Dose-Response Relationship, Drug MH - Female MH - Humans MH - Male MH - Maximum Tolerated Dose MH - Middle Aged MH - Pancreatic Neoplasms/diagnosis/*drug therapy/pathology MH - Peptidoglycan/administration & dosage/*adverse effects MH - Response Evaluation Criteria in Solid Tumors MH - Treatment Outcome PMC - PMC8183060 OTO - NOTNLM OT - Clinical trial OT - K-001 OT - Pancreatic ductal adenocarcinoma OT - Phase I study OT - Safety COIS- The authors declare that they have no competing interests. EDAT- 2021/06/09 06:00 MHDA- 2021/10/21 06:00 PMCR- 2021/06/07 CRDT- 2021/06/08 05:34 PHST- 2020/12/06 00:00 [received] PHST- 2021/05/18 00:00 [accepted] PHST- 2021/06/08 05:34 [entrez] PHST- 2021/06/09 06:00 [pubmed] PHST- 2021/10/21 06:00 [medline] PHST- 2021/06/07 00:00 [pmc-release] AID - 10.1186/s12885-021-08375-6 [pii] AID - 8375 [pii] AID - 10.1186/s12885-021-08375-6 [doi] PST - epublish SO - BMC Cancer. 2021 Jun 7;21(1):672. doi: 10.1186/s12885-021-08375-6.