Abstract
Aim: Preclinical evidence suggests that oxidized macrophage migration inhibitory factor (oxMIF) may be involved in carcinogenesis. This phase 1 study (NCT01765790) assessed the safety, tolerability, pharmacokinetics and antitumour activity of imalumab, an oxMIF inhibitor, in patients with advanced cancer using ‘3 + 3’ dose escalation. Methods: In Schedule 1, patients with solid tumours received doses from 1 to 50 mg/kg IV every 2 weeks. In Schedule 2, patients with metastatic colorectal adenocarcinoma, non-small-cell lung, or ovarian cancer received weekly doses of 10 or 25 mg/kg IV (1 cycle = 28 days). Treatment continued until disease progression, unacceptable toxicity, dose-limiting toxicity, or withdrawal of consent. Results: Fifty of 68 enrolled patients received imalumab. The most common treatment-related adverse events (TRAEs) included fatigue (10%) and vomiting (6%); four grade 3 serious TRAEs (two patients) occurred. The dose-limiting toxicity was allergic alveolitis (one patient, 50 mg/kg every 2 weeks). The maximum tolerated and biologically active doses were 37.5 mg/kg every 2 weeks and 10 mg/kg weekly, respectively. Of 39 assessed patients, 13 had stable disease (≥4 months in 8 patients). Conclusions: Imalumab had a maximum tolerated dose of 37.5 mg/kg every 2 weeks in patients with advanced solid tumours, with a biologically active dose of 10 mg/kg weekly. Further investigation will help define the role of oxMIF as a cancer treatment target.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1836-1848 |
| Number of pages | 13 |
| Journal | British Journal of Clinical Pharmacology |
| Volume | 86 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 1 2020 |
Funding
R.J. Kerschbaumer, M. Thiele and A. Schinagl were employees of Baxalta Innovations GmbH, a Takeda company, Vienna, Austria at the time that the study was conducted and were responsible for planning, analysing and evaluating biomarker and target occupancy studies. G.C. Manzur was an employee of Baxalta US Inc., a Takeda company, Cambridge, MA, USA, at the time of the study, and was involved in the clinical development of imalumab. M. Yoon of Baxalta US Inc., a Takeda company, Cambridge, MA, USA, performed the statistical analyses, was involved in the preparation of the clinical study report and reviewed the manuscript. A. Adefuye of Baxalta US Inc., a Takeda company, Cambridge, MA, USA, was involved with acquisition, analysis and interpretation of the safety data included and reviewed the manuscript. S. Sheth, P. Douillard, F. Scheiflinger, M. Azadeh and H. Glantschnig are employees of Baxalta Innovations GmbH, a Takeda company, Vienna, Austria, and reviewed the manuscript or provided additional information on the study background and methods. Medical writing support was provided by Laura McMahon of Physicians World Europe GmbH (Mannheim, Germany) and was funded by Baxalta US Inc. (a member of the Takeda group of companies, Lexington, MA, USA). R.J. Kerschbaumer, M. Thiele and A. Schinagl were employees of Baxalta Innovations GmbH, a Takeda company, Vienna, Austria at the time that the study was conducted and were responsible for planning, analysing and evaluating biomarker and target occupancy studies. G.C. Manzur was an employee of Baxalta US Inc., a Takeda company, Cambridge, MA, USA, at the time of the study, and was involved in the clinical development of imalumab. M. Yoon of Baxalta US Inc., a Takeda company, Cambridge, MA, USA, performed the statistical analyses, was involved in the preparation of the clinical study report and reviewed the manuscript. A. Adefuye of Baxalta US Inc., a Takeda company, Cambridge, MA, USA, was involved with acquisition, analysis and interpretation of the safety data included and reviewed the manuscript. S. Sheth, P. Douillard, F. Scheiflinger, M. Azadeh and H. Glantschnig are employees of Baxalta Innovations GmbH, a Takeda company, Vienna, Austria, and reviewed the manuscript or provided additional information on the study background and methods. Medical writing support was provided by Laura McMahon of Physicians World Europe GmbH (Mannheim, Germany) and was funded by Baxalta US Inc. (a member of the Takeda group of companies, Lexington, MA, USA). The study was sponsored by Baxalta US Inc. (a member of the Takeda group of companies, Lexington, MA, USA) and Baxalta Innovations GmbH, a Takeda company, Vienna, Austria. Support was also provided by a Cancer Center Support Grant (Institute for Drug Development, Cancer Therapy and Research Center at University of Texas Health Science Center San Antonio; San Antonio, TX) P30CA054174 and a grant from the National Institutes of Health/National Cancer Institute to the University of Texas MD Anderson Cancer Center, award number P30 CA016672. The study was sponsored by Baxalta US Inc. (a member of the Takeda group of companies, Lexington, MA, USA) and Baxalta Innovations GmbH, a Takeda company, Vienna, Austria. Support was also provided by a Cancer Center Support Grant (Institute for Drug Development, Cancer Therapy and Research Center at University of Texas Health Science Center San Antonio; San Antonio, TX) P30CA054174 and a grant from the National Institutes of Health/National Cancer Institute to the University of Texas MD Anderson Cancer Center, award number P30 CA016672.
Keywords
- clinical trials
- pharmacokinetics
- phase I
ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)
