MGD013 is a first-in-class bispecific tetravalent DART molecule designed to bind PD-1 and LAG-3 and restore function of exhausted T cells. Results from a phase 1 study of MGD013 have shown an acceptable safety profile and early activity in patients with advanced solid tumors and hematologic malignancies.

Results of the study were presented by Jason J. Luke, MD, of University of Pittsburgh Hillman Cancer Center in Pennsylvania, during the ASCO20 Virtual Scientific Program.

The study enrolled 50 patients into a dose escalation study from 1 mg to 1200 mg every 2 weeks, and 157 patients into a cohort expansion study at the phase 2 dose of 600 mg.

About 70% of patients experienced a treatment-related adverse event, with 23.2% experiencing grade 3 or worse events. The most commonly reported adverse events were fatigue (19%) and nausea (11%).

Among the patients in the dose escalation cohort who were evaluable for response there were 3 confirmed partial responses. One occurred in a patient with triple-negative breast cancer, 1 in a patient with mesothelioma, and 1 in a patient with gastric cancer. Eighteen patients had stable disease. This resulted in a disease control rate of 48.8%.

Dr Luke note that several cohorts in the study are ongoing, including a lymphoma cohort. He highlighted 1 patient from that cohort, a 27-year-old man with diffuse large B-cell lymphoma who had progression of disease after CAR-T cell therapy. This patient was given a single dose of MGD013 at 600 mg.

A pretreatment biopsy from the patients lymph node showed high expression of PD-1 and LAG-3. After CAR-T, the patient had CD19 loss. After his dose of MGD013, the patient was admitted to the hospital on day 11 due to grade 2 cytokine release syndrome, but had a complete response on PET scan at day 24. The patient later had allogeneic stem cell transplant and is now in remission 11 months post-MGD103.

Evaluation of MGD103 as monotherapy and in combination with FC-engineered monoclonal antibodies such as margetuximab is going, Dr Luke concluded.

Read more of Cancer Therapy Advisors coverage of the ASCO 2020 meeting by visiting the conference page.

Reference

Luke JJ, Patel MR, Hamilton EP, et al. A phase I, first-in-human, open-label, dose-escalation study of MGD013, a bispecific DART molecular binding PD-1 and LAG-3, in patients with unresectable or metastatic neoplasms. Presented at: ASCO20 Virtual Scientific Program.J Clin Oncol. 2020;38(suppl):abstr 8001.

Link:
Bispecific DART Molecule Targeting PD-1, LAG3 Active, Well-Tolerated - Cancer Therapy Advisor