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ASH 2024 | Results of a Phase I study of SEA-CD70, a CD70-directed antibody, combined with azacitidine for MDS
Nicole Grieselhuber, MD, PhD, Ohio State University, Columbus, OH, comments on the encouraging results of a Phase I dose-finding and dose-expansion study (NCT04227847) investigating SEA-CD70, a non-fucosylated CD70-directed antibody, in combination with azacitidine for patients with previously untreated high-risk myelodysplastic syndromes (HR-MDS). Dr Grieselhuber highlights that the combination was well-tolerated with manageable toxicities and will now proceed to the next phase of testing at a dose of 20 mg/kg. This interview took place at the 66th ASH Annual Meeting and Exposition, held in San Diego, CA.
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Transcript
SEA-CD70 is a non-fucosylated monoclonal antibody targeted against CD70. CD70 is expressed on the surface of blasts in MDS and AML. It’s believed to be involved with proliferation and survival of the leukemic cells. The antibody’s proposed mechanisms are antibody-dependent cytotoxicity, antibody-dependent phagocytosis, and complement-dependent cytotoxicity...
SEA-CD70 is a non-fucosylated monoclonal antibody targeted against CD70. CD70 is expressed on the surface of blasts in MDS and AML. It’s believed to be involved with proliferation and survival of the leukemic cells. The antibody’s proposed mechanisms are antibody-dependent cytotoxicity, antibody-dependent phagocytosis, and complement-dependent cytotoxicity. It’s also thought that it may interfere with the binding of CD70 to the CD27 ligand that induces signaling. It’s known that azacitidine treatment actually increases expression of CD70 on the blasts, and so this provided a rationale to combine these two agents.
So in this study, it was a Phase I dose-finding and dose-escalation study of SEA-CD70 with azacitidine in previously untreated high-risk MDS patients. And we found that this combination was tolerable with manageable toxicities at both the 10 and 20 mg per kg doses.
And excitingly, while this is an early-phase study, and was not powered for other endpoints, we did see an overall response rate of 44% across both cohorts. And encouragingly, over half of the patients had blast clearance. So we think this is really exciting evidence of the efficacy of this combination. In addition, 16% of our patients were actually able to proceed to allogeneic stem cell transplant. We think this is also encouraging, especially given that the median age of our study participants was 72. So we’re really excited about this combination. We’re going to proceed with an expansion cohort at the 20 mg per kg dose, and we look forward to additional development of this drug in myeloid malignancies.
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