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, a journal of the American Society of Hematology, which
highlights interim results of an ongoing Phase 1/2 clinical trial
of flotetuzumab in patients with acute myeloid leukemia (AML).
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.
As described in the article titled “Flotetuzumab as
Salvage Immunotherapy for Refractory Acute Myeloid
Leukemia,” 88 AML patients were enrolled in the Phase 1/2
trial as of November 1, 2019, including 42 in dose escalation and
46 treated with flotetuzumab at the recommended Phase 2 dose (RP2D)
of 500ng/kg/day. The majority (56%) had adverse risk by ELN 2017
criteria and 36% had secondary AML. Patients were heavily
pretreated, with a median of three lines of prior therapy (range
1-9). Collectively, this group of patients represents a
poor-prognosis population having few effective therapies and an
otherwise limited life expectancy.
The most common treatment-related adverse event (TRAE) was
infusion-related reaction/cytokine release syndrome (IRR/CRS), the
majority reported as grade 1-2. Stepwise dosing during week 1,
pre-treatment with dexamethasone, prompt use of tocilizumab and
temporary dose reductions/interruptions successfully prevented
severe IRR/CRS, resulting in acceptable tolerability.
As described in the publication, of 50 evaluable patients with
relapsed or refractory AML, 30 patients entered the study with no
prior response to induction therapy (primary induction failure AML
or PIF AML) or having relapsed within six months of achieving an
initial remission (early relapsed AML or ER AML), a combined
population with poor prognosis and high unmet medical needs. This
PIF/ER AML subset of patients showed a 16.7% (5/30) complete
remission (CR) rate and a combined CR and complete remission with
partial hematological recovery (CRh) rate of 26.7% (8/30) following
flotetuzumab treatment. In contrast, only one of 20 patients with
late relapsed AML achieved a CR following flotetuzumab treatment.
PIF/ER patients who achieved CR/CRh showed median overall survival
(OS) of 10.2 months (range 1.87-27.27), with 6- and 12-month
survival rates of 75% (95% CI, 0.450-1.05) and 50% (95% CI,
0.154-0.846).
“The response to flotetuzumab in primary induction failure and
early relapsed AML is consistent with our previously published
data1 that an IFN-γ-related inflammatory gene expression signature
in the AML bone marrow correlated with lack of response to
induction chemotherapy but was associated with a greater likelihood
to respond 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, and a co-author on the current paper. “AML is a highly
heterogeneous disease. Our translational studies provided a strong
mechanistic basis for studying flotetuzumab in these AML patients,
who currently have few treatment options.”
“The results recently published in Blood support our decision to
conduct a pivotal study of flotetuzumab in the specific subset of
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. “Moreover, the
translational research provides a strong mechanistic basis for
studying flotetuzumab in these AML patients, who currently have few
treatment options. Our single arm clinical trial is ongoing as an
expansion of the Phase 1/2 study, for which we plan to enroll a
total of up to 200 patients. We plan to present interim results
later this year.”
1 “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 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.
The discovery by the Rutella lab of an immunological gene signature
in the AML tumor microenvironment forms the basis for a potential
predictive biomarker for further clinical validation.
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. Data from the Phase 1/2 clinical study of
flotetuzumab in patients with primary induction failure / early
relapse (PIF/ER) AML were presented in December 2019 at
the American Society of Hematology (ASH) Annual Meeting.
MacroGenics is conducting a single-arm, registration-enabling
clinical study to evaluate flotetuzumab in up to 200 patients with
PIF/ER AML, with complete remission (CR) and CR with partial
hematological recovery (CRh) as the primary endpoint. The study
will be conducted as a continuation of the ongoing Phase 1/2 study
(NCT02152956; to be updated). The FDA has granted orphan drug
designation to flotetuzumab for the treatment of AML.
About MacroGenics, Inc.
MacroGenics is a clinical-stage biopharmaceutical company
focused on discovering and developing innovative monoclonal
antibody-based therapeutics for the treatment of cancer. The
Company generates its pipeline of product candidates primarily from
its proprietary suite of next-generation antibody-based technology
platforms, which have applicability across broad therapeutic
domains. For more information, please see the Company's website
at www.macrogenics.com. MacroGenics and
the MacroGenics logo are trademarks or registered
trademarks of MacroGenics, Inc.
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###
CONTACT:
Jim Karrels, Senior Vice President, CFO
MacroGenics, Inc.
1-301-251-5172, info@macrogenics.com
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