- Flotetuzumab demonstrated 29.4% complete response rate in evaluable primary refractory AML patients
- Translational studies suggest potential strategy for biomarker-based patient selection
The Phase 1 dose expansion study of flotetuzumab in relapsed/refractory patients with acute myeloid leukemia (AML) enrolled 31 patients at the recommended Phase 2 dose of 500 ng/kg/day by continuous infusion with a lead-in dosing strategy. The goal of the expansion cohort study was to evaluate the safety and preliminary anti-leukemic activity of flotetuzumab, optimize delivery and supportive care, including the management of cytokine release syndrome (CRS), and to define the pharmacokinetic (PK) and pharmacodynamic (PD) activity of flotetuzumab.
In a companion oral presentation,
In addition to the oral presentations described above, two posters relating to flotetuzumab were presented. The first poster (#2738) was “Management of Cytokine Release Syndrome in AML Patients Treated with Flotetuzumab, a CD123 × CD3 Bispecific DART® Molecule for T-cell Redirected Therapy.” This poster provided further characterization of the experience with IRR/CRS in patients treated with flotetuzumab, approaches to management of IRR/CRS, and evaluation of the association between various clinicopathologic features, potential biomarkers and IRR/CRS. The use of multi-step lead-in dosing as well as early intervention with tocilizumab helped to ameliorate IRR/CRS, and initial translational studies suggest that the frequency of CD4+ (but not CD8+) T cells at baseline could potentially serve as a biomarker to help identify patients who are at increased risk for developing more severe IRR/CRS.
A second poster (#4065) titled “Bone Marrow T Cell Changes by Multiplex IHC after Treatment with Flotetuzumab, a CD123 × CD3 Bispecific DART® Protein, in a Primary Refractory t-AML Patient” presented a case study of an AML patient treated with flotetuzumab in the Phase 1 study who experienced a complete response on flotetuzumab therapy, as well as correlative translational studies. The patient experienced a CR after one cycle of therapy, with an associated increase in CD3+ and CD3+CD8+ T cells in the bone marrow biopsy. After an additional cycle of therapy, the bone marrow continued in CR. An increase in CD8+ T cells persisted beyond the cessation of flotetuzumab dosing. The patient remained in CR with no additional therapy for approximately 7 months.
“The oral presentations and posters related to the Phase 1 expansion cohort of flotetuzumab suggest that patients with refractory AML, a population with very few therapeutic options, may be more likely to respond to flotetuzumab within the cohort of relapse/refractory patients. Further, initial translational studies implicate an IFN-γ gene signature in the bone marrow as a potential biomarker-based approach for patient selection,” said
Flotetuzumab (also known as MGD006 and S80880) is a clinical-stage molecule that recognizes both CD123 and CD3. CD123, the interleukin-3 receptor alpha chain, has been reported to be over-expressed on cancer cells in a wide range of hematological malignancies, including AML and MDS. The primary mechanism of action of flotetuzumab is believed to be its ability to redirect T lymphocytes to kill CD123-expressing cells. To achieve this, the DART molecule combines a portion of an antibody recognizing CD3, an activating molecule expressed by T cells, with an arm that recognizes CD123 on the target cancer cells.
Flotetuzumab is currently being evaluated in the U.S. and
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Jim Karrels, Senior Vice President, CFO MacroGenics, Inc.1-301-251-5172, firstname.lastname@example.org Karen Sharma, Managing Director MacDougall Biomedical Communications1-781-235-3060, email@example.com
Source: MacroGenics, Inc.