MULTOMAB

Rationale

In oncology, monoclonal antibodies (mABs) have become key players. Still, their pharmacokinetics (PK) are largely unexplained. Since PK might predict for treatment outcome or toxicity, we aim to map the PK of mABs and factors that influence it.

Objective

To set up a bank of prospectively collected blood samples for pharmacokinetic analyses of monoclonal antibodies.
Study design: Prior to every cycle and until the next treatment line a blood sample for pharmacokinetic analyses will be withdrawn. Optionally, additional blood samples will be withdrawn in the first week after the first treatment cycle.

Study population

Adult patients planned to receive a monoclonal antibody as anti-cancer treatment.

Main study parameters/endpoints

The primary study endpoint is the trough level of different monoclonal antibodies over time. Secondary endpoints include the quantity of antibodies against the therapeutic monoclonal antibody and intrinsic characteristics of peripheral blood immune cells (in PBMC).

Study objectives

• To set up a bank of prospectively collected blood samples from patients treated with monoclonal antibodies. 

Secondary Objectives: 

• To correlate pharmacokinetic (PK) parameters with effectiveness and toxicity of monoclonal antibodies. 
• To determine the influence of immunogenicity on PK. 
• To determine the influence of peripheral blood immune cell characteristics on PK and effectiveness and toxicity of monoclonal antibodies. 
• Explore the characteristics of exosomes before start of treatment, during treatment, and after disease progression. 
• To assess the course of PK and peripheral mononuclear blood cells characteristics shortly after the first treatment cycle, i.e. within 1 week.
• To validate an assay that can determine serum concentrations of monoclonal antibodies.

Collaboration within Erasmus MC:

• Dr. J.E.M.A. Debets, PhD, laboratory of Tumor Immunology
• Prof. J.G.J.V. Aerts, department of Pulmonary Diseases

Collaboration outside Erasmus MC:

Amphia Ziekenhuis Breda:
Dr. C.H. van der Leest, MD/PhD
Department of Pulmonology
Molengracht 21, 4818 CK Breda, the Netherlands

Elisabeth-TweeSteden ziekenhuis, Tilburg :
Dr. J.S. Kloover, MD/PhD
Department of Pulmonology
Elisabeth-TweeSteden hospital, Tilburg :
Doctor Deelenlaan 5, 5042 AD Tilburg, the Netherlands

Kantonsspital St. Gallen:
M. Joerger, MD/PhD
Department of Medical Oncology & Hematology
Cantonal Hospital, 9007 St.Gallen, Switzerland

Hurkmans, DP et al. A prospective cohort study on the pharmacokinetics of nivolumab in metastatic non-small cell lung cancer, melanoma, and renal cell cancer patients. J Immunotherap Cancer. 2019 Jul 19;7(1):192

Basak, EA et al. Correlation between nivolumab exposure and treatment outcomes in non-small-cell lung cancer. Eur J Cancer. 2019 Mar; 109:12-20.

Kunert, A et al. CD45RA+CCR7- CD8 T cells lacking co-stimulatory receptors demonstrate enhanced frequency in peripheral blood of NSCLC patients responding to nivolumab. J Immunother Cancer. 2019 Jun 8;7(1):149

Prof A.H.J. Mathijssen, MD/PhD, principal investigator

Coordinating Investigators

• Karlijn de Joode, MD
• Daan P. Hurkmans, MD, MSc. Biomedicine
• Edwin Basak, BSc
• Stijn L.W. Koolen, PharmD, PhD

Writing commitee

• Prof. J.G.J.V. Aerts, MD/PhD
• Dr. J.E.M.A. Debets, PhD 
• Dr. S. Bins, MD/ PhD

Contact us:

• multomab@erasmusmc.nl
• a.mathijssen@erasmusmc.nl
• k.dejoode@erasmusmc.nl