CD40/CD47 inhibitor shows promise in high-risk MDS and AML

The combination of the investigational agent SL-172154 with azacitidine delivered promising efficacy results among participants with newly diagnosed acute myeloid leukaemia (AML) or higher-risk myelodysplastic syndrome (MDS) in a phase 1b trial.

SL-172154 is a bifunctional fusion protein targeting CD40 and CD47. In a phase 1b study, this agent was tested in combination with azacitidine as a combination regimen for patients with previously untreated AML or higher-risk MDS. The current interim analysis presented findings from 2 dose expansion cohorts, including 23 participants with high-risk MDS and 21 with TP53-mutated AML. Prof. Amer Zeidan (Yale University, CT, USA) presented safety and efficacy data from this assessment [1].

The overall response rate was 67% in the MDS group and 43% in the AML participant group. In the MDS group, the complete remission rate was 42% compared with 29% in the AML group. After 5.3 months of follow-up in the MDS group and 4.2 months in the AML group, the median duration of overall response, complete remission, and overall survival had not been reached.

There were 9 cases of SL-172154-related serious adverse events, including infusion-related reactions (n=3) and cytokine release syndrome (n=2). Dr Zeidan and colleagues noted that the safety profile of the combination regimen was comparable to that of azacitidine alone, except for any grade infusion-related reactions (42%), any grade fatigue 10–17%, and cytokine release syndrome in the MDS arm (8%).

Dr Zeidan concluded that SL-172154 plus azacitidine had an acceptable safety profile and promising anti-tumour activity in these participant cohorts with poor prognostic features.

1. Zeidan AM, et al. Phase 1B study of SL-172154, a bi-functional fusion protein targeting CD47 and CD40, with azacitidine, in previously untreated acute myeloid leukaemia and higher-risk myelodysplastic syndromes. P773, EHA congress 2024, 13–16 June, Madrid, Spain.

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Posted on 12 August 2024