On May 27, 2020 MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, reported plans for a clinical study intended to support registration in the U.S. of flotetuzumab, an investigational, bispecific CD123 x CD3 DART molecule for patients with acute myeloid leukemia (AML) who are refractory to induction therapy (Press release, MacroGenics, MAY 27, 2020, View Source [SID1234558531]).
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Informed by recent discussions with the U.S. Food and Drug Administration (FDA), the Company plans a single-arm, registration-enabling clinical study to evaluate flotetuzumab in up to 200 patients with primary induction failure (PIF) or early relapse (ER) AML. The study will be conducted as a continuation of the ongoing Phase 1/2 study (NCT02152956; to be updated). Complete remission (CR) and CR with partial hematological recovery (CRh) will be the primary endpoint of the pivotal study. Key secondary endpoints will include durability of response and other supportive clinical endpoints.
"Patients with AML who are refractory to induction therapy or relapse early after an initial response have limited treatment options," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "Clinical and translational data suggest that such refractory AML patients may be responsive to immunotherapy with flotetuzumab. We are very pleased to advance our first DART molecule into a pivotal study with an opportunity to address a significant unmet need."
Data from the Phase 1/2 clinical study of flotetuzumab in patients with PIF/ER AML were presented in December 2019 at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. A CR/CRh rate of 27% (8 of 30) was observed in the intent-to-treat population. The most common treatment-related adverse event was infusion-related reaction/cytokine release syndrome that occurred in all patients and was mostly of short duration and mild to moderate (grade 1 or 2) in severity.
About Acute Myeloid Leukemia
AML is a hematological malignancy characterized by differentiation arrest and uncontrolled clonal proliferation of neoplastic precursors that prevent normal bone marrow hematopoiesis. Nearly 20,000 new cases of AML are diagnosed in the U.S. each year, with a median age of 69 years at diagnosis. Approximately 40-50% of newly diagnosed patients fail to achieve a complete remission with intensive induction therapy (primary induction failure) or experience disease recurrence after a short remission duration (<6 months; early relapsed). A very small number of these patients are expected to respond to salvage therapy. Although new targeted agents have been approved for the treatment of frontline or relapsed/refractory AML in recent years, approximately 50% of patients have no known targetable mutations.
About Flotetuzumab
Flotetuzumab (also known as MGD006) is a clinical-stage bispecific DART molecule that recognizes both CD123 and CD3. CD123, the interleukin-3 receptor alpha chain, has been reported to be over-expressed on malignant cells in AML and other hematologic malignancies. 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 cells. The FDA has granted orphan drug designation to flotetuzumab for the treatment of AML.