Phase 1 dose escalation and expansion trial of the bispecific CD47 inhibitor and CD40 agonist Fc-fusion protein SL-172154 (SIRPα-Fc-CD40L) in patients with higher-risk myelodysplastic syndrome or acute myeloid leukemia.

What was studied

This phase 1 trial tested SL-172154, a drug that blocks CD47 and boosts CD40. It was given alone or with azacitidine (AZA). The patients had acute myeloid leukemia (AML) or higher-risk myelodysplastic syndrome (HR-MDS). The trial enrolled 33 patients with HR-MDS and 48 with AML. Dose escalation had 37 patients. Expansion had 44. The expansion used 3 mg/kg with AZA in untreated HR-MDS or TP53-mutant AML.

What they found

Infusion-related reactions were the most common drug-linked toxicity. They caused a dose-limiting toxicity at 6 mg/kg. Complete remission occurred in 10 of 24 HR-MDS patients. It occurred in 6 of 21 TP53-mutant AML patients. Median overall survival was 11.0 months in HR-MDS and 11.7 months in AML. Of the HR-MDS patients in remission, 6 of 10 had complete cytogenetic remission. Among the AML patients in remission, it was 3 of 6.

What it means for patients

The authors say SL-172154 plus AZA was generally well tolerated. They say it gave favorable remission rates. They add that overall survival was not substantially better than historical benchmarks.

Why it is not certain yet

This was an early phase 1 trial with no control group. The abstract compares survival with past benchmarks, not with a control arm. Subgroups were small. The AML survival range was very wide.

Source

Phase 1 dose escalation and expansion trial of the bispecific CD47 inhibitor and CD40 agonist Fc-fusion protein SL-172154 (SIRPα-Fc-CD40L) in patients with higher-risk myelodysplastic syndrome or acute myeloid leukemia.

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