This is a first in human, prospective, multicentric, nonrandomized, open-label study to investigate the safety, tolerability, preliminary efficacy, pharmacokinetics, pharmacodynamics and immunogenicity of the Fc-optimized antibody FLYSYN as monotherapy in adult subjects.
Cohort 1: Patient 1-3: FLYSYN 0.5 mg/m² body surface area (BSA) day 1 Cohort 2: Patient 4-6: FLYSYN 0.5 mg/m² body surface area (BSA) day 1 FLYSYN 1.0 mg/m² BSA day 2 Cohort 3: Patient 7-9: FLYSYN 0.5 mg/m² body surface area (BSA) day 1, FLYSYN 4.5 mg/m² BSA day 2 Cohort 4: Patient 10-12 and 13-18: FLYSYN 0.5 mg/m² body surface area (BSA) day 1, FLYSYN 14.5 mg/m² BSA day 2 Cohort 5: Patient 19-21: FLYSYN 0.5 mg/m² body surface area (BSA) day 1, FLYSYN 44.5 mg/m² BSA day 2 Cohort 6: Patient 22-24 and 25 -31: FLYSYN 0.5 mg/m² body surface area (BSA) day 1, FLYSYN 14.5 mg/m² BSA day 2, FLYSYN 15 mg/m² BSA day 15, FLYSYN 15 mg/m² BSA day 29
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
31
Cohort 1: Patient 1-3: FLYSYN 0.5 mg/m² BSA\* day 1 Cohort 2: Patient 4-6: FLYSYN 0.5 mg/m² BSA day 1 FLYSYN 1.0 mg/m² BSA day 2 Cohort 3: Patient 7-9: FLYSYN 0.5 mg/m² BSA day 1, FLYSYN 4.5 mg/m² BSA day 2 Cohort 4: Patient 10-12 and 13-18: FLYSYN 0.5 mg/m² BSA day 1, FLYSYN 14.5 mg/m² BSA day 2 Cohort 5: Patient 19-21: FLYSYN 0.5 mg/m² BSA day 1, FLYSYN 44.5 mg/m² BSA day 2 Cohort 6: Patient 22-24 and 25-31: FLYSYN 0.5 mg/m² BSA day 1, FLYSYN 14.5 mg/m² BSA day 2, FLYSYN 15 mg/m² BSA day 15, FLYSYN 15 mg/m² BSA day 29 \* The maximum upper limit for calculation of antibody dose is fixed at a body surface of 2.0 m², even if the calculated body surface exceeds this. In this study DLT are defined as the following treatment-related adverse events or laboratory abnormalities, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03.
University Hospital Tuebingen
Tübingen, Baden-Wurttemberg, Germany
University Hospital Ulm
Ulm, Baden-Wurttemberg, Germany
Hannover Medical School
Hanover, Lower Saxony, Germany
University Hospital of Heidelberg
Heidelberg, Germany
Incidence and severity of adverse events (AE) (CTCAE V 4.03)
Time frame: until 28 days (i.e. Visit7, day 29) after last dosing
Incidence and severity of adverse events (AE) (CTCAE V 4.03)
Time frame: until 180 days (i.e.Visit 11, day 180) after last dosing
Pharmacokinetics and pharmacodynamics
Time frame: Visit 1 to 13
Immunogenicity of FLYSYN based on both absolute (number and percentage of subjects who develop HAMA/HAHA) and semi-quantitative (HAMA/HAHA titer determination of confirmed positive samples) assessments
Time frame: BSL; Visits 5-7;9-13
Absolute and percent change from baseline in measurements of B, T, and NK cell populations and activation
For evaluation of the status of the immune system, B, T, and NK cells will be measured frequently throughout the study (immune status). The percentage and absolute numbers as well as the absolute and percent changes from baseline of NK cells will be evaluated (determination of absolute NK cell numbers). If feasible, CD16 and CD69 expression on NK cells will be evaluated at baseline and after antibody exposition (NK cell activation). Pending sample availability, endogenous antibody titers (e.g., tetanus titers) will be measured from remaining PK back-up samples in order to gain information about the influence of FLYSYN treatment on normal plasma cells and immunity.
Time frame: Visits 1;3;4;5;9
Change in cytokines from baseline
Time frame: Visits 1-3;5 +6
Overall response rate, defined as MRD negativity or reduction of at least one log step,
Time frame: BSL; Visits1;4-13
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University of Leipzig Medical Center
Leipzig, Germany
Duration of response, time to MRD progression (log step), time to relapse
Time frame: BSL; Visits1;4-13
Absolute change from baseline in overall quality of life scores (EORTC QLQ C-30)
Time frame: Visit 1, Visit 6,Visit 9,Visit 10, Visit 11, Visit 12, Visit 13