The publication, Development and Preliminary Clinical Activity of PD-1-Guided CTLA-4 Blocking Bispecific DART Molecule, highlights key findings from the ongoing Phase 1 trial of MGD019 first-in-human study of patients with advanced solid tumors (NCT03761017) as well as data from mechanistic studies. Findings in mechanistic studies demonstrated that cells co-expressing PD-1 and CTLA-4 are abundant in the tumor microenvironment (TME) compared to normal tissues, supporting PD-1 and CTLA-4 co-blockade in treating solid tumor cancers. This observation suggests that targeting dual PD-1/CTLA-4-expressing cells may also provide an opportunity for increased selectivity of checkpoint blockade in the TME, while relatively reducing effects in normal tissues.
In vitro studies demonstrated that MGD019 may provide complete blockade of PD-1 together with tunable inhibition of CTLA-4, with greatly enhanced blockade of CTLA-4 activity on dual-antigen expressing cells, a potential advantage over PD-1 or CTLA-4 blockade with individual monoclonal antibodies. In addition, MGD019 was well tolerated in non-human primates following repeated intravenous (IV) administrations (four weekly doses) of MGD019 at dose levels of 10, 40 and 100 mg/kg, well exceeding the highest non-severely toxic dose reported for the combination of nivolumab and ipilimumab in this species.
These mechanistic data formed the basis for the on-going, first-in-human study demonstrating clinical activity and correlated pharmacodynamics. At the cutoff date of
“Treatment with PD-1 and CTLA-4 inhibitors such as nivolumab and ipilimumab has been effective in several cancer indications; however, the combination is associated with significant toxicity,” said
MGD019 is an investigational, bispecific DART molecule that was designed to enable blockade of two immune checkpoint molecules expressed on T cells, PD-1 and CTLA-4. Based upon the establishment of a recommended Phase 2 dose (RP2D) from a dose escalation study, MGD019 is initially being evaluated in a dose expansion study in microsatellite-stable colorectal cancer and non-small cell lung cancer.
About MacroGenics, Inc.
MacroGenics is a biopharmaceutical company focused on developing and commercializing 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, the MacroGenics logo and DART are trademarks or registered trademarks of MacroGenics, Inc.
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Source: MacroGenics, Inc.