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ASH 2024 | CTX112, a next-generation allogeneic CD19 CAR T-cell, in patients with R/R B-cell malignancies
In this video, Chan Cheah, MBBS, FRACP, FRCPA, DMSc, Linear Clinical Research and Sir Charles Gairdner Hospital, Perth, Australia, discusses the potential of CTX112, a novel allogeneic CRISPR-Cas9 engineered CD19 CAR T-cell, as a more potent and persistent treatment for relapsed/refractory (R/R) B-cell malignancies. Dr Cheah highlights that the edits made to CTX112 allow for standard lymphodepleting chemotherapy while maintaining good activity, and further summarizes findings from a recent study of this agent. This interview took place at the 66th ASH Annual Meeting and Exposition, held in San Diego, CA.
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Transcript (AI generated)
Yeah, so CTX112 is an interesting allogeneic CD19 CAR-T construct. It is made by CRISPR-Cas9 gene editing of both TCR and Regnase to basically enhance the persistence and proliferation capacity of allo-CAR-T’s, because one of the problems with allo-CAR-T compared to auto-CAR-T is that you get slightly less persistence of the product. And that has resulted in, that in other studies has led to issues with durability of responses, and has led to other approaches such as enhancing lymphodepleting chemotherapy...
Yeah, so CTX112 is an interesting allogeneic CD19 CAR-T construct. It is made by CRISPR-Cas9 gene editing of both TCR and Regnase to basically enhance the persistence and proliferation capacity of allo-CAR-T’s, because one of the problems with allo-CAR-T compared to auto-CAR-T is that you get slightly less persistence of the product. And that has resulted in, that in other studies has led to issues with durability of responses, and has led to other approaches such as enhancing lymphodepleting chemotherapy. So using higher doses of fludarabine and or cyclophosphamide, or incorporating other mechanisms of T-cell depletion, such as alemtuzumab style regimens to try and improve the quality of lymphodepletion. But the problem with those kinds of approaches is they lead to increased toxicity. So if you have to deplete T-cells more to allow your CAR T-cells to proliferate, sorry, endogenous T-cells more to allow your CAR T-cells to proliferate, then that will have deleterious impacts for the patient in terms of immunosuppression and risk of infection. And so I think the edits made in the CTX112 are nice because they allow standard LD chemo, but still can result in excellent activity. And we presented data for around, I think 20 patients that were treated on this Phase I dose escalation study. So there have been four dose levels that have been looked at and a range of patients with different kinds of lymphoma, including primarily large cell, but also some mantle, marginal zone, follicular lymphoma. And we’re seeing encouraging response rates. We’re seeing a number of patients attain CRs and a number of those patients with CR out past 12 months, so I think that’s encouraging. The safety profile has been pretty acceptable so far. We haven’t seen very high rates of CRS, despite the edits that were made to increase proliferation and enhance the persistence. So I think that’s encouraging as well, and only one DLT observed so far in the study. So I think this is a very promising agent. Clearly more follow-up and a large number of patients is required to really understand where this is going to fit in and how this can be taken forward. And enrollment to this study is ongoing.
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Disclosures
Dizal: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Other: Travel expenses, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; BeiGene: Consultancy, Honoraria, Other: travel expenses, Speakers Bureau; Lilly: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Other: Travel expenses, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Research Funding, Speakers Bureau; MSD: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Menarini: Consultancy, Honoraria; Sobi: Consultancy, Honoraria; Regeneron: Consultancy, Honoraria; Genmab: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding.
