Benzinga | Dec 6, 2020 04:12PM EST

MacroGenics Presented Flotetuzumab Data Showing Median Duration of Response of 8.13 Months in Patients with Refractory Acute Myeloid Leukemia at ASH 2020

MacroGenics, Inc. (NASDAQ:MGNX) today announced updated results from a single-arm, registrational study of flotetuzumab, an investigational, bispecific CD123 CD3 DART® molecule, in patients with primary induction failure (PIF) and early relapsed (less than six months, or ER6) acute myeloid leukemia (AML). The data were presented at the 62nd Annual Meeting of the American Society of Hematology (ASH) taking place December 5-8, 2020.

In the open label study of flotetuzumab, 44 AML patients had disease classified as either PIF or ER6. Of these patients, 72.7% (32 of 44) had adverse risk cytogenetics by ELN Risk Stratification (2017). Patients were treated with flotetuzumab at the recommended Phase 2 dose (RP2D) of 500 ng/kg/day by continuous infusion. Data were reported as of the cut-off date of November 10, 2020. The study is currently ongoing, with a total of up to 200 patients planned for enrollment for registrational purposes.

The median time to achieve a response to flotetuzumab was one cycle (range of 1-3 cycles). Responses, including complete remission (CR), CRh (CR with partial hematological recovery) and CRi (CR with incomplete hematological improvement) per a modified International Working Group (IWG) Response Criteria for AML, are summarized in the table below.

PIF/ER (n=44) PIF (n=27) ER6 (n=17)CR/CRh 25.0% (11) 33.3% (9) 11.8% (2)CR/CRh/Cri 31.8% (14) 37.0% (10) 23.5% (4)HSCT 57.1% (8/14) 70.0% (7/10) 25.0% (1/4)Median Duration of Response 8.13 mos.(n=14) 15.2 mos.(n=10) 2.4 mos.(n=4)As shown in the table, over 50% of responders (8 of 14) successfully received allogeneic hematopoietic stem cell transplantation (HSCT) as consolidation therapy with durable remission (median not reached). Also, among those PIF/ER6 patients who achieved remission (CR, CRh or CRi), the median duration of response was 8.13 months, with a median overall survival of 10.7 months. Within the PIF/ER6 population, five of ten patients with TP53MUT AML achieved CR/CRh/CRi responses, three of whom went on to receive HSCT. More detailed flotetuzumab clinical data in the TP53MUT AML population is available via a separate poster presentation at ASH (see "TP53 Abnormalities Correlate with Immune Infiltration and Associate with Response to Flotetuzumab Immunotherapy in Acute Myeloid Leukemia", Session 617).

The most common treatment-related adverse event (TRAE) was infusion-related reaction/cytokine release syndrome (IRR/CRS), which occurred in all patients. However, most CRS events observed were of short duration and mild to moderate (Grade 1 or 2) in severity, with only a single Grade 3 event reported.

"For the approximately 50% of AML patients who fail primary induction therapy or relapse within six months of an initial response, there is no standard of care among the available treatment regimens. Historically, these patients have CR/CRh rates to subsequent interventions in the range of only 5-12% with a median overall survival of approximately 3.5 months. A remission rate of 32% with good duration and a manageable safety profile observed to date in the ongoing registrational study of flotetuzumab in this extremely challenging patient population is very encouraging," said Ibrahim Aldoss, M.D., Assistant Professor of Hematology/HCT at City of Hope Comprehensive Cancer Center.

In addition to the above data provided in an oral presentation, five additional presentations related to flotetuzumab and AML have or will be presented at ASH.

"We are very encouraged by the updated results from this study, and continue to enroll patients in this single arm, registrational trial," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "Especially encouraging is the duration of response we've seen to date in this otherwise fragile population of patients for whom no approved therapies exist."