A phase I study of the safety and activity of K-001 in patients with advanced pancreatic ductal adenocarcinoma
Open Access
- 7 June 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in BMC Cancer
- Vol. 21 (1), 1-9
- https://doi.org/10.1186/s12885-021-08375-6
Abstract
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. 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). 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%. 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. NCT02720666. Registered 28 Match 2016 - Retrospectively registered.Keywords
Funding Information
- Development Center for Medical Science & Technology National Health Commission of the People’s Republic of China (2018ZX09711001-007-010)
This publication has 36 references indexed in Scilit:
- Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced CancerThe New England Journal of Medicine, 2012
- Gemcitabine Plusnab-Paclitaxel Is an Active Regimen in Patients With Advanced Pancreatic Cancer: A Phase I/II TrialJournal of Clinical Oncology, 2011
- FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic CancerThe New England Journal of Medicine, 2011
- Phase III Study Comparing Gemcitabine Plus Cetuximab Versus Gemcitabine in Patients With Advanced Pancreatic Adenocarcinoma: Southwest Oncology Group–Directed Intergroup Trial S0205Journal of Clinical Oncology, 2010
- Gemcitabine Plus Bevacizumab Compared With Gemcitabine Plus Placebo in Patients With Advanced Pancreatic Cancer: Phase III Trial of the Cancer and Leukemia Group B (CALGB 80303)Journal of Clinical Oncology, 2010
- Dose Escalation Methods in Phase I Cancer Clinical TrialsJNCI Journal of the National Cancer Institute, 2009
- Gemcitabine Plus Capecitabine Compared With Gemcitabine Alone in Advanced Pancreatic Cancer: A Randomized, Multicenter, Phase III Trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology GroupJournal of Clinical Oncology, 2007
- Irinotecan Plus Gemcitabine Results in No Survival Advantage Compared With Gemcitabine Monotherapy in Patients With Locally Advanced or Metastatic Pancreatic Cancer Despite Increased Tumor Response RateJournal of Clinical Oncology, 2004
- New Guidelines to Evaluate the Response to Treatment in Solid TumorsJNCI Journal of the National Cancer Institute, 2000
- The European Organization for Research and Treatment of Cancer QLQ-C30: A Quality-of-Life Instrument for Use in International Clinical Trials in OncologyJNCI Journal of the National Cancer Institute, 1993