Summary
Interim results of the first-in-human clinical study of FLYSYN, a novel Fc-optimized antibody, for the treatment of acute myeloid leukemia (AML), were presented at 2019 ASH Annual Meeting (Abstract 3928). The phase I study of FLYSYN is being conducted at multiple centers in Germany (University Hospitals of Tübingen, Ulm, Heidelberg, Hanover and Leipzig) and will enroll up to 31 AML patients that have achieved a complete morphological remission but display minimal residual disease (MRD).
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Original Article
First-in-Human Study of Fc-Optimized Antibody FLYSYN for Acute Myeloid Leukemia
Oncology Times
Interim results of the first-in-human clinical study of FLYSYN, a novel Fc-optimized antibody, for the treatment of acute myeloid leukemia (AML), were presented at 2019 ASH Annual Meeting (Abstract 3928). The phase I study of FLYSYN is being conducted at multiple centers in Germany (University Hospitals of Tübingen, Ulm, Heidelberg, Hanover and Leipzig) and will enroll up to 31 AML patients that have achieved a complete morphological remission but display minimal residual disease (MRD).
The poster reported on an interim analysis of 21 adult patients (median age: 60 years) who were treated in 5 cohorts receiving a single administration of increasing doses of FLYSYN (0.5 to 45 mg/m² body surface area).
FLYSYN was very well-tolerated and only one patient experienced grade 3 neutropenia, which was potentially related to FLYSYN treatment. Other adverse events of grade 1 or 2 included gastrointestinal toxicities and laboratory abnormalities that were manageable with supportive care. No dose-limiting toxicities occurred during the dose-escalation phase and no anti-drug antibodies were detected after treatment.
A total of seven patients (33%) achieved an MRD response defined as a log reduction of expression of an MRD marker gene and one patient achieved an enduring complete molecular remission (MRD-negative) for more than 1 year.
“Our data indicate that FLYSYN is safe and very well-tolerated. The preliminary efficacy data are promising. We are very much looking forward to further test FLYSYN as monotherapy for MRD-positive AML patients,” commented Prof. Helmut Salih, principle investigator of the study and Medical Director of the Clinical Collaboration Unit Translational Immunology at Tübingen University Hospital.
The chimeric and Fc-optimized IgG1 antibody FLYSYN binds specifically and with high avidity to the human fms-like tyrosine kinase 3 (FLT3). An increased expression of this cell surface receptor is measured on myeloid precursor cells in 70-100 percent of AML patients, while only small amounts of FLT3 are expressed on monocytes and progenitor stem cells, thereby avoiding off-target effects and stem cell toxicity. Therefore, FLT3 is a suitable and highly selective target for therapeutic antibodies to treat leukemia patients. FLYSYN contains a genetic optimization of its Fc-part, resulting in optimized binding to natural killer (NK) cells and thus substantially improved antibody-dependent cell-mediated cytotoxicity (ADCC). FLYSYN is a monospecific antibody for the treatment of AML patients at a stage of MRD. Most AML patients achieve complete remission with MRD after regular chemotherapy, but the majority relapses to AML within several months, requiring additional courses of chemotherapy or stem cell transplantation. FLYSYN is intended to delay or prevent such relapse in AML patients with MRD.