Conference Coverage

Antibody targeting ‘do not eat me’ signals is active in AML, MDS


 

REPORTING FROM ASCO 2019

– A novel antibody against CD47 – the “do not eat me” protein – is well tolerated and active in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), according to initial results of a phase 1b study.

Combined with azacitidine, the antibody Hu5F9-G4 (5F9) produced an overall response rate of 64% in untreated AML (9 of 14 patients) and 91% in untreated MDS (10 of 11 patients), according to investigator David A. Sallman, MD, of Moffitt Cancer Center, Tampa, Fla.

With a median follow-up of 3.8 months, none of those patients had yet progressed on the 5F9/azacitidine combination, Dr. Sallman reported during a poster presentation at the annual meeting of the American Society of Clinical Oncology.

A maximum tolerated dose of 5F9 plus the hypomethylating agent was not reached in the study, according to the investigators.

“This was a well-tolerated and safe combination, with encouraging efficacy data in this small cohort that hasn’t been followed for too, too long,” Tara L. Lin, MD, of the University of Kansas Cancer Center, Kansas City, said during a poster discussion session.

“Most interesting is the fact that the combination seems to eliminate the leukemia stem cell population in those patients who respond,” she added.

The fact that 5F9 plus azacitidine eradicated leukemia stem cells in responding patients provides a mechanism for potential long-term durability of response, according to Dr. Sallman and his colleagues.

This first-in-class antibody targets CD47, a “do not eat me” macrophage checkpoint that is overexpressed on tumors, enabling immune invasion, they reported.

However, since CD47 is also expressed on older red blood cells, 5F9 is associated with transient anemia in the first cycle of treatment, Dr. Sallman told attendees at the poster discussion session.

“We do mitigate that with a priming dose of 5F9 that saturates these old red blood cells,” he said. “Over time, going along with the response, the patients have marked hemoglobin improvement, and we do not see worsening of other infection-related complications or cytopenias outside of anemia.”

Based on these results, expansion cohorts have been initiated in both AML and MDS, according to the investigators’ report.

When asked if 5F9 could be tolerable as part of more intensive regimens for fit patients, Dr. Sallman said there are a “whole host of combinations” that may possibly make sense.

“How chemotherapies and other novel agents impact these ‘eat me’ signals – I think some of that needs to be further investigated to come up with the most rational combination,” he said during a question and answer session.

Research funding for the study came from Forty Seven and the California Institute for Regenerative Medicine. Dr. Salman reported having no relationships to disclose. Study coauthors reported relationships with Abbvie, Agios, Celgene, Incyte, and Novartis, among other companies.

SOURCE: Sallman DA et al. ASCO 2019, Abstract 7009.

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