MacroGenics Announces Flotetuzumab Publication in Blood Advances

— Role of TP53 abnormalities in immunotherapy response in AML highlighted

ROCKVILLE, MD, Oct. 15, 2020 (GLOBE NEWSWIRE) --  

MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, today announced the publication of a manuscript in Blood Advances, a journal of the American Society of Hematology.  This represents the third publication of flotetuzumab data in 2020. Flotetuzumab (also known as MGD006), is an investigational, clinical-stage bispecific DART® molecule that recognizes both CD123 on leukemic cells and CD3 on T cells, with the intended result of T-cell-mediated killing of leukemic blasts. This most recent publication reports on the role of flotetuzumab in the immunotherapy of TP53-positive acute myeloid leukemia (AML).

It has previously been shown1 that an inflammatory (IFN-γ-related) gene expression signature in patients with AML correlated with a lack of response to induction chemotherapy. The same gene signature was shown to be associated with an increased probability of this subset of patients to respond to flotetuzumab. As further described in the article titled “TP53 Abnormalities Correlate with Immune Infiltration and Associate with Response to Flotetuzumab Immunotherapy in AML,” AML with TP53 abnormalities was also associated with immune infiltration in the tumor microenvironment (TME); moreover, patients with TP53 abnormalities derived benefit from flotetuzumab immunotherapy.

“Previous translational studies demonstrated that patients who failed to respond to induction therapy (primary induction failure, or PIF, AML) or those who relapsed within six months of achieving an initial remission (early relapsed, or ER, AML) had an immune-infiltrated TME that not only associated with resistance to standard-of-care chemotherapy regimens, but also with response to flotetuzumab,” said Sergio Rutella, M.D., Ph.D., FRCPath, John van Geest Cancer Research Centre, College of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom. “Included in this PIF/ER AML population are patients harboring TP53 abnormalities, a particularly difficult to treat subset of AML associated with poor prognosis. Interestingly, these patients who responded poorly when treated with standard-of-care chemotherapy regimens appeared to benefit from flotetuzumab therapy.” 

“The results published today in Blood Advances, combined with data from previous articles published in Blood and Science Translational Medicine, further support our decision to conduct a pivotal study of flotetuzumab in AML patients who have previously experienced either a primary induction failure or an early relapse when treated with standard-of-care chemotherapy regimens. These individuals represent approximately 40-50% of all AML patients,” said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. “Our single arm clinical trial is ongoing as an expansion of the Phase 1/2 study, for which we plan to enroll up to 200 patients. We plan to present interim results at a medical conference later this year.” 1 “Flotetuzumab as Salvage Immunotherapy for Refractory Acute Myeloid Leukemia,” Blood, 2020; and “Immune Landscapes Predict Chemotherapy Resistance and Immunotherapy Response in Acute Myeloid Leukemia,” Science Translational Medicine, 2020.

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 PIF) or experience disease recurrence after a short remission duration (