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ASH 2024 | CTX112, a next-generation allogeneic CD19 CAR-T product, for treating R/R B-cell malignancies
Armin Ghobadi, MD, Washington University School of Medicine, St. Louis, MO, reports the preliminary results of a Phase I dose escalation study (NCT05643742) investigating CTX112, a next-generation allogeneic CRISPR-Cas9 engineered CD19 CAR T-cell product, for treating relapsed/refractory (R/R) B-cell malignancies. Dr Ghobani highlights the unique nature of this product, outlining the five modifications used to enhance the function of the CAR T-cells. This interview took place at the 66th ASH Annual Meeting and Exposition, held in San Diego, CA.
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Transcript (AI-generated)
So CTX112 is an allogeneic CD19 CAR from CRISPR Therapeutics. We are reporting the preliminary results of 12 patients in the dose escalation phase of the study using CD19 allogeneic CAR called CTX112 in patients with relapsed refractory B-cell malignancies.
So a little bit about CTX112. CTX112, as I mentioned, is an allogeneic CD19 second-generation CAR...
So CTX112 is an allogeneic CD19 CAR from CRISPR Therapeutics. We are reporting the preliminary results of 12 patients in the dose escalation phase of the study using CD19 allogeneic CAR called CTX112 in patients with relapsed refractory B-cell malignancies.
So a little bit about CTX112. CTX112, as I mentioned, is an allogeneic CD19 second-generation CAR. Normal healthy donors are used to manufacture this. And the beauty of this second generation is it has five edits. One is getting rid of T-cell receptors to prevent graft-versus-host disease, getting rid of HLA, Ron beta-2 microglobulin to prevent allorejection of the T-cells. And one of the, this is actually the first product in clinic that has this modification. It’s called REGNASE-1, knocking out of REGNASE-1. When you do this, actually, you are removing the internal brake for T-cells. So make the CAR-T cells, super CAR-T cells, basically. And also TGF beta receptor 2 knockout to prevent the external brake in the tumor to enhance the function of CAR T-cells. And the CAR molecules are inserted in the T-cell T-rac locus. So those are the five modifications here.
This product is allogeneic off the shelf CD19 as I mentioned, used in the relapsed refractory B-cell malignancies and wide variety of histologies, large B-cell lymphoma, mantle cell lymphoma, and follicular lymphoma. We are reporting in first 12 patients in a dose escalation. In terms of safety, it’s very safe. CRS rate was around 60%, with no grade two or three or higher CRS in this first 12 patients. And ICANS also happened in one-third of patients, but no grade three or higher ICANS. In terms of efficacy, we saw impressive efficacy of roughly around 70%, with complete response rate of 50%. And the dose escalation, remember, we started with the lower dose. So that’s impressive for an allogeneic CAR and the dose escalation seeing that response. So that’s for CTX-112. I’m very impressed with this product. So we’re going to enroll more patients and hopefully we report about the outcome of those in the near future.
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Disclosures
ATARABio: Consultancy; Genentech: Research Funding; Bristol Myers Squibb: Consultancy; CRISPR Therapeutics: Consultancy; Wugen Inc: Consultancy; Kite (Gilead company): Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Research Funding.
