ASH 2024 | A Phase I trial of SEA-CD70, a CD70-directed antibody, in combination with azacitidine for HR-MDS

This is another multi-institutional Phase I study, open label of anti-CD70 antibody. It’s a non-fucosylated anti-CD70 antibody developed by Seattle Genetics and now under the auspices of Pfizer. This antibody targets CD70 and we know that CD70 is enriched in myeloid blasts and targeting CD70 has been an area of interest. So on this Phase I trial, we have previously reported the data on monotherapy with anti-CD70 antibody. And now at this conference, we are reporting data on combination therapy with azacitidine. Now this drug has been tested at two different dose levels, 10 mg per kilogram dose level and also a 20 milligram per kilogram dose level in combination with standard of care azacitidine therapy, which is day one through seven every 28 days. And this drug, the antibody drug, the investigational drug is given every 15 days until there is toxicity or loss of efficacy. So on this trial, the most important thing is this is a Phase I study. We are looking at safety outcomes. And safety was generally comparable to single agent azacitidine therapy. So it is no different. And the investigational drug is not adding to the safety endpoints. Now, we did notice that in about 16% of patients, there were infusion-related reactions, which is expected in an antibody drug. So that relates to safety. And when it comes to efficacy, what we noticed is that about 44% of patients achieved an overall response rate. And the overall response rate is defined as CR plus CR with partial hematologic recovery and also PR. So 44% saw an overall response rate. And this study specifically only enrolled high-risk MDS patients, and that too only patients who had more than 5% blast, up to 19% of blast. And blast clearance rate was something we looked at, and blast clearance rate was about 56% in these patients. So how did this translate? I think the translation into clinically meaningful outcome is about 16% of these patients have moved on to a transplant, and that’s, you know, we all know that in high-risk MDS patients, transplant is what makes the difference. So about 16% of patients went into a transplant and the overall survival rates were about 19.6 months, which is incredible in such a high-risk population with high-grade MDS along with mutations. And it’s important to note that these patients were enriched for high-risk cytogenetics. About 50% of these patients were high-risk cytogenetics. So seeing a 20-month overall survival in this group, I believe, is remarkable. And this just, you know, we are looking at exploring a Phase III trial, and that would be, you know, that would add to understanding of this drug and also understanding whether it makes a difference over single agent standard azacitidine therapy. We know that most therapies, I mean, high-grade MDS is considered the graveyard of most drugs because most drugs do not work. And we’ve seen that with PD-1 targeting therapies. We’ve seen that with, in fact, CD47 targeting therapies. So CD70 is the exciting new target that we’re exploring. It at least seems to have the activity or the efficacy and I mean a lot to be said about waiting until a Phase III trial. We just you know Phase I trials because of the sample size and they’re not having a comparator arm you know they the data we have to take it with a grain of salt and we just need to wait for Phase III trials.

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