Population Pharmacokinetics of Sibrotuzumab, A Novel Therapeutic Monoclonal Antibody, in Cancer Patients

  title={Population Pharmacokinetics of Sibrotuzumab, A Novel Therapeutic Monoclonal Antibody, in Cancer Patients},
  author={Charlotte Kloft and E U Graefe and Paul Tanswell and Andrew Mark Scott and R Hofheinz and Andree Amelsberg and Mats O. Karlsson},
  journal={Investigational New Drugs},
Population pharmacokinetics of sibrotuzumab, a humanized monoclonal antibody directed against fibroblast activation protein, were determined after multiple intravenous infusions of dosages ranging from 5mg/m2 to an absolute dose of 100mg, in patients with advanced or metastatic carcinoma. In total, 1844 serum concentrations from 60 patients in three Phase I and II clinical studies were analyzed. The structural model incorporated two disposition compartments and two parallel elimination pathways… 

Refinement of the Population Pharmacokinetic Model for the Monoclonal Antibody Matuzumab

Simulations revealed that variability in concentration-time profiles for minimum and maximum steady-state concentrations was reduced to a marginal extent by a proposed dose adaptation in the population pharmacokinetic model for matuzumab.

Population Pharmacokinetics of Cetuximab in Patients With Squamous Cell Carcinoma of the Head and Neck

Clinical dose adjustments beyond the approved body surface area‐based dosing of cetuximab may be warranted in patients with extreme deviations of their actual body weight from ideal body weight.

Population Pharmacokinetics of Therapeutic Monoclonal Antibodies

Many features of the population pharmacokinetics of currently used therapeutic mAbs are similar, despite differences in their pharmacological targets and studied patient populations.

Pharmacokinetics, immunogenicity and safety of bivatuzumab mertansine, a novel CD44v6-targeting immunoconjugate, in patients with squamous cell carcinoma of the head and neck.

Dose individualization according to body size (weight or body surface area) was found to be appropriate and is recommended for the novel immunoconjugate and a dose proportional increase in the exposure of BIWI 1 and deconjugated BI WI 1 was observed.

Clinical Pharmacokinetics of Therapeutic Monoclonal Antibodies

The parenteral administration, slow tissue distribution and long elimination half-life are the most pronounced clinical pharmacokinetic characteristics of mAbs.

Infliximab Pharmacokinetics in Inflammatory Bowel Disease Patients

Both body weight and sex were found to influence infliximab pharmacokinetics, and its clearance increased thrice in the presence of ATI, notably with an elimination half-life of approximately 3 weeks.

Population Pharmacokinetics of Humanized Monoclonal Antibody HuCC49ΔCH2 and Murine Antibody CC49 in Colorectal Cancer Patients

Clinical trial designs with at least 3 measurements of antibody disposition were found to be better than an empirical direct observation method for the optimal prediction of surgery time.

Influence of Antigen Mass on the Pharmacokinetics of Therapeutic Antibodies in Humans

This review focuses on the influence of antigen mass on the pharmacokinetics of therapeutic antibodies quantified by pharmacokinetic modelling in humans, which led to non-linear elimination decay in 50 publications.

Pharmacokinetic comparison of a diverse panel of non-targeting human antibodies as matched IgG1 and IgG2 isotypes in rodents and non-human primates

While antibody isotype had no significant impact on the pharmacokinetics, the CDRs do alter the profile, and there is an inverse correlation between the neonatal Fc receptor (FcRn) affinity and pharmacokinetic performance.

Pharmacokinetic characteristics of therapeutic antibodies

  • J. Wohlrab
  • Biology, Medicine
    Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG
  • 2015
Therapeutic antibodies behave differently in terms of absorption, distribution and elimination compared to conventional drugs, and pharmacokinetic conditions can be optimized by coadministration of, for example, methotrexate.



Population pharmacokinetics of antifibroblast activation protein monoclonal antibody F19 in cancer patients.

The pharmacokinetics of antistromal mAbF19 were well defined in these two studies with different solid tumour types, and were comparable with those of other murine monoclonal antibodies that do not bind to normal tissue antigens or blood cells.

A Phase I dose-escalation study of sibrotuzumab in patients with advanced or metastatic fibroblast activation protein-positive cancer.

  • A. ScottG. Wiseman L. Old
  • Medicine, Biology
    Clinical cancer research : an official journal of the American Association for Cancer Research
  • 2003
Repeat infusions of the humanized anti-FAP antibody sibrotuzumab can be administered safely to patients with advanced FAP-positive cancer, and a maximum tolerated dose was not reached.

Pharmacokinetics of indium-111-labeled B72.3 monoclonal antibody in colorectal cancer patients.

Mean time parameters provide a new approach to plasma pharmacokinetics of radiolabeled Mabs that may show important patient differences affecting diagnosis or treatment and may provide an opportunity to select another specific Mab with an increased chance for successful diagnosis and treatment.

Pharmacokinetic model of iodine-131-G250 antibody in renal cell carcinoma patients.

  • A. LohG. Sgouros C. Divgi
  • Biology, Medicine
    Journal of nuclear medicine : official publication, Society of Nuclear Medicine
  • 1998
Parameter sensitivity analysis showed that a change in the transfer rate constant from serum to the rest of the body had the greatest effect on serum cumulative activity and that the rate constant for excretion had the largest effect on whole-body cumulative activity.

Population Pharmacokinetics and Pharmacodynamics of the Anti-CD11a Antibody hu1124 in Human Subjects with Psoriasis

The pharmacokinetics of hu1124, a human anti-CD11a antibody, were investigated in human subjects with psoriasis and one of the receptor-mediated pharmacokinetic/pharmacodynamic models which was developed describes the dynamic interaction of hU1124 binding to CD11a, resulting in the removal of hi1124 from the circulation and reduction of cell surface CD 11a.

Pharmacokinetics of Gemtuzumab Ozogamicin, an Antibody‐Targeted Chemotherapy Agent for the Treatment of Patients with Acute Myeloid Leukemia in First Relapse

The pharmacokinetics of gemtuzumab ozogamicin has been characterized in AML patients receiving doses at the proposed therapeutic level and no relationship was found between plasma concentration and response at the recommended dose.

Stromal Antigen Targeting by a Humanised Monoclonal Antibody: An Early Phase II Trial of Sibrotuzumab in Patients with Metastatic Colorectal Cancer

Unconjugated sibrotuzumab (BIBH 1), which is a humanised version of the murine anti-FAP mAb F19, was investigated for its anti-tumour activity, safety and pharmacokinetics and was well tolerated and safe.

The pharmacokinetics, antigenicity, and fusion-inhibition activity of RSHZ19, a humanized monoclonal antibody to respiratory syncytial virus, in healthy volunteers.

RSHZ19 had low plasma clearance and a half-life of approximately 23 days, similar to native IgG, and the ability of plasma to inhibit virus-induced fusion of VERO cells previously infected with RS Long strain virus was evaluated.

Serological analysis of human anti-human antibody responses in colon cancer patients treated with repeated doses of humanized monoclonal antibody A33.

Using a novel, highly sensitive BIACORE method, this work was able to distinguish these two types of HAHAs in patients while on antibody treatment, allowing patients to be removed from study prior to the onset of severe infusion-related adverse events.