MacroGenics Announces Publication of Flotetuzumab Interim Phase 1/2 Clinical Trial Results in Blood

Rhea-AI Summary

MacroGenics, Inc. (NASDAQ: MGNX) announced the publication of interim results from a Phase 1/2 trial of flotetuzumab, aimed at treating acute myeloid leukemia (AML). The trial enrolled 88 patients, revealing a 16.7% complete remission rate in those with primary induction failure or early relapse. Flotetuzumab, a bispecific DART molecule, effectively targets CD123 on leukemic cells and CD3 on T cells, leading to significant T-cell mediated responses. The company plans to expand its trial to 200 patients, with interim results expected later this year, highlighting potential for a pivotal study in this high-unmet-need population.

Positive

• Flotetuzumab shows a 16.7% complete remission rate in primary induction failure/early relapse AML patients.
• Ongoing trial expansion to include up to 200 patients, indicating confidence in drug's efficacy.
• Interim results to be presented later this year, potentially boosting investor sentiment.

Negative

• Most common adverse events include infusion-related reactions, though manageable.
• Only one patient with late relapsed AML achieved complete remission, indicating limited effectiveness for that subgroup.

ROCKVILLE, MD, Sept. 22, 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, 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.

Cautionary Note on Forward-Looking Statements

Any statements in this press release about future expectations, plans and prospects for the Company, including statements about the Company's strategy, future operations, clinical development of the Company's therapeutic candidates, milestone or opt-in payments from the Company's collaborators, the Company's anticipated milestones and future expectations and plans and prospects for the Company and other statements containing the words "subject to", "believe", "anticipate", "plan", "expect", "intend", "estimate", "project", "may", "will", "should", "would", "could", "can", the negatives thereof, variations thereon and similar expressions, or by discussions of strategy constitute forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the uncertainties inherent in the initiation and enrollment of future clinical trials, expectations of expanding ongoing clinical trials, availability and timing of data from ongoing clinical trials, expectations for the timing and steps required in the regulatory review process, expectations for regulatory approvals, the impact of competitive products, our ability to enter into agreements with strategic partners and other matters that could affect the availability or commercial potential of the Company's product candidates, business or economic disruptions due to catastrophes or other events, including natural disasters or public health crises such as the novel coronavirus (referred to as COVID-19), and other risks described in the Company's filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the Company's views only as of the date hereof. The Company anticipates that subsequent events and developments will cause the Company's views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so, except as may be required by law. These forward-looking statements should not be relied upon as representing the Company's views as of any date subsequent to the date hereof.

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CONTACT:

Jim Karrels, Senior Vice President, CFO
MacroGenics, Inc.
1-301-251-5172, info@macrogenics.com

FAQ

What are the results of the MGNX Phase 1/2 trial of flotetuzumab?

The Phase 1/2 trial showed a 16.7% complete remission rate in patients with primary induction failure or early relapse AML.

How many patients were involved in the MGNX flotetuzumab trial?

The trial enrolled 88 patients as of November 1, 2019.

What is the next step for MacroGenics regarding flotetuzumab?

MacroGenics plans to expand the trial to include up to 200 patients and present interim results later this year.

What is the mechanism of action for flotetuzumab?

Flotetuzumab is a bispecific DART molecule that targets CD123 on leukemic cells and CD3 on T cells, facilitating T-cell mediated killing of leukemic blasts.

What were the most common adverse events reported in the flotetuzumab trial?

The most common adverse events were infusion-related reactions/cytokine release syndrome, primarily grade 1-2.