Abstract 1473
Background
IGF-1R is over-expressed by neoplastic cells in many human cancers, associated with tumorigenesis, metastasis and treatment resistance. W0101 is a First-in-Class Antibody Drug Conjugate (ADC), designed for treatment of patients with tumors overexpressing membrane IGF-1R. Preclinically, internalization and anti-tumor activity of W0101 was shown in models expressing membrane IGF-1R (AACR 2018). To select potential responders to W0101 we developed a prototype immuno-histochemistry assay using a proprietary monoclonal antibody detecting a specific epitope on human IGF-1R, different from that of W0101. Using this test, we evaluated the membrane expression of IGF-1R in samples of squamous non-small-cell lung cancer (sqNSCLC), head-and-neck cancer and ER+ HER2- invasive breast cancer. This assay is currently used for retrospective assessment of patients included in this study. Here we present the design of a phase I/II international, multicentre, open label dose escalation and dose expansion study of intravenous infusion of W0101 in patients with advanced or metastatic solid tumors.
Trial design
This phase I/II consists of 2 parts: an initial dose escalation phase (I) followed by an expansion cohort (s) phase (II). In the dose escalation phase, 2 schedules of administration in 2 successive cohorts of patients will be assessed: Q2W schedule (A1) and a Q3W or Q4W schedule (A2). The first dose and the schedule of administration in cohort A2 will be determined using all safety and pharmacokinetics data generated in cohort A1 and using a PK/PD model. The phase I will allow to determine the Maximum Tolerated Dose and Schedule (MTDS) and to characterize dose-limiting toxicities (DLTs). The dose-toxicity relationships established via a Bayesian Logistic Regression Model will support the dose escalation process and will be used to assess the MTDS and recommended doses for expansion. Following completion of the dose escalation phase, the expansion phase will enroll up to 4 cohorts of patients prospectively tested for overexpression of IGF-1R to assess preliminary efficacy. A Simon design will be used for futility analysis.
Clinical trial identification
NCT03316638.
Legal entity responsible for the study
Pierre Fabre Medicament Represented by Institut de Recherche Pierre Fabre.
Funding
Has not received any funding.
Editorial Acknowledgement
Disclosure
F. Cruzalegui, F. Ausseil, O. Delfour, J. Besse, B. Akla, S. Gautier, A. Passioukov, R. Roche, M. Pavlyuk: Full-time employee: Institut de Recherche Pierre Fabre. G. Zorza: Pierre-Fabre full-time employee. J. Adam, M. Lacroix-Triki: Funded the immunohistochemistry study performed at Gustave Roussy: Institut de Recherche Pierre Fabre. All other authors have declared no conflicts of interest.
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