On September 20, 2020 MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, reported clinical data from the dose escalation portion of a Phase 1 clinical trial of MGD019 (Press release, MacroGenics, SEP 20, 2020, View Source [SID1234565382]). 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) (Free ESMO Whitepaper) Virtual Congress 2020 on September 20, 2020, by Dr. Manish R. Sharma, Associate Director of Clinical Research at START Midwest in Grand Rapids, Michigan.
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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 (Free ESMO Whitepaper) 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 View Source
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.