Tandem Meetings 2023 | LBA: update on Phase I study of rapcabtagene autoleucel in patients with R/R DLBCL

Rapcabtagene autoleucel is a next-generation CD19 CAR T-cell product. It’s an autologous CAR T-cell product and it actually uses the same sort of CD19 construct as the Novartis product tisagenlecleucel. However, it uses a novel manufacturing sort of paradigm to produce a CAR T-cell product that has increased stemness, more naive. But the idea being that if you change the manufacturing parameters, you can lead to a better quality CAR T-cell product that is more fit. So this manufacturing platform is called T-Charge, and it basically is a very rapid manufacturing platform with the cells sort of being cultured for less than two days as part of the manufacturing process. And so this was a Phase I clinical trial to identify a safe dose level. And so they treated patients at sort of multiple different dose level. Ultimately they identified a dose level of 12.5 by 10 to the sixth total CAR T-cells as the one to move forward. But I would note that this is a significantly lower dose of CAR T-cells than the products out there. Again, suggesting that a more naive CAR T-cell product, you don’t need to give as many cells and they can sort of engraft and expand in vivo in the patient, which is what we saw in this clinical trial.

So looking specifically at that dose level two, which has been identified for future investigation and for Phase II and Phase III clinical trials in terms of safety and toxicity, again, there was low rates of grade three to form cytokine release syndrome. And overall the safety profile was in line with other CAR T-cell products that we see for diffuse large B-cell lymphoma.

Looking specifically at the quality of this sort of T-cell product. And they actually sort of compared it to tisagenlecleucel. You know, you find that this product has increased sort of stemness, naiveness, a high percentage of T stem cell memory like CAR T-cells, which again, we think might be important to both the cytotoxicity, so the ability to kill the tumor cells, but also the persistence. And persistence can be important in terms of mitigating relapse.

So I think that this is a very exciting platform, really trimming the manufacturing down to a limited period, giving a lower dose of CAR T-cells, but getting high response rates by using a more naive CAR T-cell profile. And so this product also based on this Phase I study with the dose identified will be moving forward to larger Phase II clinical trials to better get a sense of the efficacy.