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
In brief
SL-172154 plus azacitidine produced remission in 43% of higher-risk MDS patients
In this phase 1 trial, 10 of 24 patients with higher-risk myelodysplastic syndrome achieved complete remission with SL-172154 plus azacitidine; six of 21 patients with TP53-mutated acute myeloid leukemia did too. Median survival was 11.0 and 11.7 months, respectively, without substantial improvement over historical benchmarks; infusion reactions were common, and the regimen's benefit needs confirmation.
- Journal
- Cancer (Q1)
- Published
- 1 October 2026
- Study design
- Phase 1 (first-in-human) trial
- Evidence level
- Level 4, Very Low (CEBM 4)
- Authors
- Naval G Daver, Amer M Zeidan, Anthony S Stein, Joshua F Zeidner, Keri Maher, Emily Curran, et al.
- PMID
- 42829896
- DOI
- 10.1002/cncr.70626
Why clinicians should know about it
- Picked for Hematology (paper of the day, 9 October 2026): Phase 1 trial of CD47/CD40 bispecific in AML/MDS
Abstract
BACKGROUND: This clinical trial sought to determine whether SL-172154 could be combined safely and improve the efficacy of azacitidine (AZA) in patients with higher-risk myelodysplastic syndrome (HR-MDS) or acute myeloid leukemia (AML). METHODS: Dose escalation: doses of 1, 3, and 6 mg/kg SL-172154 was evaluated as monotherapy or in combination with AZA in patients with relapsed, refractory HR-MDS or AML. Expansion: a SL-172154 dose that could be safely combined with AZA was evaluated in patients with previously untreated HR-MDS or TP53 mutant (TP53m) AML. OBJECTIVES: safety, efficacy, pharmacokinetics, pharmacodynamics, and immunogenicity. RESULTS: Eighty-one patients with HR-MDS (n = 33) or AML (n = 48) were enrolled in dose escalation (n = 37) or expansion (n = 44). Infusion-related reaction was the most common SL-172154-related toxicity and led to a dose limiting toxicity at 6 mg/kg. A dose of 3 mg/kg SL-172154 plus AZA was evaluated in patients with previously untreated HR-MDS (n = 21 with TP53m and n = 3 with TP53 wild type) and AML (n = 21 with TP53m). CD47 and CD40 engagement by SL-172154 was detected on leukemic blasts, myeloid, and lymphoid cells. Complete remission (CR) was achieved in 10 of 24 (43%) HR-MDS and six of 21 (29%) TP53m AML patients with median overall survival (OS) of 11.0 months (95% CI, 5.0-15.6) and 11.7 months (95% CI, 1.97-NE), respectively. Of patients in a CR, six of 10 HR-MDS and three of six TP53m AML patients achieved complete cytogenetic CR. CONCLUSIONS: SL-172154 plus AZA was generally well tolerated with favorable CR rates in pts with TP53m HR-MDS or AML, although without substantial improvement in OS when compared to historical benchmarks for AZA or AZA/VEN, respectively.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.