MacroGenics Announces Presentation of MGD019 Phase 1 Data at the ESMO Virtual Congress 2020

Rhea-AI Summary

MacroGenics (MGNX) announced promising clinical data from the Phase 1 trial of MGD019, a bispecific PD-1 × CTLA-4 DART molecule targeting advanced solid tumors. The trial showed that MGD019 was well-tolerated, with no dose-limiting toxicities reported. Of the 18 evaluable patients at doses ≥ 3.0 mg/kg, 4 objective responses were noted, including a complete response in metastatic castration-resistant prostate cancer. The company plans to expand the study in patients with microsatellite stable colorectal cancer and non-small cell lung cancer at a recommended Phase 2 dose of 6.0 mg/kg.

Positive

• MGD019 demonstrated early signals of activity in tumors typically resistant to checkpoint inhibition.
• No dose-limiting toxicities were observed during the trial.
• Objective responses included one complete response in metastatic castration-resistant prostate cancer.

Negative

• Some Grade 3 adverse events were reported at the 10.0 mg/kg dose level.
• Trial involved a heavily pre-treated patient population, which might affect the generalizability of results.

• MGD019 well-tolerated with early signals of activity in advanced solid tumors not typically responsive to checkpoint inhibition
• Recommended Phase 2 dose established for MSS CRC, NSCLC expansion cohorts
• Presentation is available on-demand as part of the ESMO Virtual Congress 2020 

ROCKVILLE, MD, Sept. 20, 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 clinical data from the dose escalation portion of a Phase 1 clinical trial of MGD019. The proffered paper session titled, “A Phase 1, First-in-Human, Open-Label, Dose Escalation Study of MGD019, an Investigational Bispecific PD-1 × CTLA-4 DART® Molecule in Patients with Advanced Solid Tumors,” was presented orally at the European Society for Medical Oncology (ESMO) Virtual Congress 2020 on September 20, 2020, by Dr. Manish R. Sharma, Associate Director of Clinical Research at START Midwest in Grand Rapids, Michigan.

MGD019, a bispecific PD-1 × CTLA-4 DART molecule, was designed to enhance CTLA-4 blockade on dual-expressing, tumor-infiltrating lymphocytes compared to a PD-1/CTLA-4 monoclonal antibody (mAb) combination therapy, while maintaining maximal PD-1 blockade on all PD-1-expressing cells. 

Forty-three patients were enrolled in the Phase 1 dose escalation study of MGD019 within a dose range of 0.03 – 10.0 mg/kg, administered every three weeks initially, in a population of heavily pre-treated patients representing a broad range of different types (23) of solid tumors. There were no dose-limiting toxicities (DLTs). A total of 28 patients were treated at doses ≥ 3.0 mg/kg administered every three weeks initially. MGD019 was well-tolerated in patients who received less than 10 mg/kg; the most common treatment-related adverse events over this dosing range were pruritus (23.3%), arthralgia (18.6%), fatigue (18.6%), rash (18.6%), nausea (16.3%) and infusion-related reaction (16.3%). Several Grade 3 adverse events were observed at the 10.0 mg/kg level; however, none were considered dose limiting.

In this study, sustained peripheral PD-1 blockade was evident at doses ≥ 1.0 mg/kg.  In addition, dose-dependent upregulation of the inducible costimulator (ICOS) molecule was evident in treated patients, including those who responded to MGD019 therapy.  This is consistent with the previously reported observation that anti-CTLA-4 therapy increases the frequency of CD4 T cells expressing the ICOS molecule.¹

Of the 18 evaluable patients who received doses ≥ 3.0 mg/kg as of the July 21, 2020 cut-off date, four objective responses have been reported in this trial, including a confirmed complete response in metastatic castration-resistant prostate cancer (mCRPC), confirmed partial responses in microsatellite stable colorectal cancer (MSS CRC) and metastatic type AB thymoma, and an unconfirmed partial response in serous fallopian tube carcinoma.

“We are especially encouraged by the evidence of anti-tumor activity in patients treated with MGD019 who have cancers typically unresponsive to checkpoint inhibition. In addition, we are very pleased that MGD019 was well tolerated,” said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. “Based on the results presented today, we plan to expand the study initially in patients with MSS CRC and checkpoint-naïve non-small cell lung cancer at the recommended Phase 2 dose of 6.0 mg/kg.”

These results are available on-demand as part of the ESMO Virtual Congress 2020 Proffered Paper - Investigational Immunotherapy session on September 20, 2020 (Presentation # 1020O). In addition, Dr. Sharma’s slides can be accessed under "Events & Presentations" in the Investor Relations section of MacroGenics’ website at http://ir.macrogenics.com/events.cfm.

About MGD019

MGD019 is an investigational bispecific DART molecule that was designed to enable co-blockade of two immune checkpoint molecules co-expressed on T cells, PD-1 and CTLA-4.

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.

¹Cancer Immunol Res. 2013 Oct; 1(4): 229–234.

CONTACT:

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

FAQ

What were the results of the MGD019 Phase 1 trial?

The Phase 1 trial of MGD019 reported no dose-limiting toxicities and showed objective responses in several patients, including one complete response.

What is the next step for MGD019 after the Phase 1 trial?

MacroGenics plans to expand the study in patients with microsatellite stable colorectal cancer and non-small cell lung cancer at a recommended Phase 2 dose of 6.0 mg/kg.

What types of tumors is MGD019 targeting?

MGD019 is targeting advanced solid tumors, particularly those not typically responsive to checkpoint inhibition.

When was the MGD019 trial presented?

The results of the MGD019 trial were presented at the ESMO Virtual Congress on September 20, 2020.

What is the significance of the MGD019 results for patients?

The results suggest potential anti-tumor activity in patients with cancers usually unresponsive to current checkpoint inhibitors, which could be groundbreaking.