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First-in-Human Study of CD200 Blockade With Samalizumab in CLL

By: Sarah Campen, PharmD
Posted: Friday, October 18, 2019

Samalizumab, a novel recombinant humanized monoclonal antibody targeting CD200, reduced tumor burden in a majority of patients with advanced chronic lymphocytic leukemia (CLL) in a first-in-human phase I trial. No dose-limiting toxicity was observed, and adverse events were considered “manageable.” The results of the study were published in the Journal for ImmunoTherapy of Cancer.

“The findings of this study provide proof-of-concept for targeted inhibition of the immune checkpoint CD200, as samalizumab appears to have provided significant therapeutic benefit to some CLL patients despite a suboptimal dosing schedule,” stated Daruka Mahadevan, MD, PhD, of the University of Arizona Cancer Center in Tucson, and colleagues.

In this open-label trial, 23 patients with advanced CLL and 3 patients with multiple myeloma were assigned to one of seven dose-level cohorts, receiving a single dose of samalizumab at 50 to 600 mg/m2 intravenously every 28 days. A total of 21 patients received more than one treatment cycle, and the maximum tolerated dose was not reached.

Decreased tumor burden was observed in 64% of patients with CLL, with 2 patients having more than a 50% reduction, 1 patient with CLL achieving a durable partial response, and 16 patients with CLL having stable disease. However, all three patients with myeloma who received the study drug had disease progression. The researchers also found that samalizumab produced dose-dependent decreases in CD200 expression on CLL cells and decreased frequencies of circulating CD200-positive, CD4-positive T cells.

Adverse events were generally mild to moderate. The most common drug-related grade 3 or 4 treatment-emergent adverse events were blood disorders—anemia, neutropenia, and thrombocytopenia; they were reported in three patients (12%).

Despite the positive results observed in patients with CLL, the researchers believe the blood concentrations of samalizumab that were reached are “insufficient to completely saturate cell-surface CD200 on the CLL cells,” explained Dr. Mahadevan and colleagues. “Further clinical investigation should include additional dosing regimens, including further dose escalation and more frequent dosing of samalizumab.”

Disclosure: The study authors’ disclosure information can be found at jitc.biomedcentral.com.



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