ASH 2020 | Phase I/II trial of P-BCMA-101 CAR-T cell therapy in R/R myeloma

P-BCMA CAR T-cells were selected for an oral presentation at ASH this year, abstract number 134. And the P-BCMA CAR T is a novel product, it’s manufactured with a transposon which holds a large cargo capacity and preferentially produces T-stem CAR T-cell phenotypes, which then includes a safety switch and a drug selection gene. The important thing about the stem cell memory T-cells is that they’re self-renewing, they’re multipotent, long-lived CAR-Ts. And what multiple studies have shown is that they have a better clinical response, more gradual cell killing with less CRS, and then a better duration of response. And what’s interesting about what’s going to be presented at ASH this year is that the manufacturing process for P-BCMA has actually changed to utilize a smaller plasmid, which we’re calling a nanoplasmid, which ultimately enhances a transposition.

Ultimately with this CAR, I’ll talk a little bit about the study, this is a 3+3 design with multiple cohorts. So what you’re going to see in the presentation is more on the single administration arm. There were multiple different arms, including a cyclic A and B arm where patients received one third of the dose, and then two thirds as separate dosing. And then in cyclic B, they received a third, a third, a third. Three additional cohorts are too small to report on at this time but those include giving rituximab at day -12 and day -5 and then Q eight weeks after infusion to decrease the production of anti-CAR-T antibodies. And then there are two lenalidomide arms where patients receive lenalidomide before conditioning therapy and then after T-cell infusion and then an arm where they receive lenalidomide in the same fashion, but also before collection to increase the input material.

So with this CAR-T it’s similar to other CAR-Ts that are out there in terms that the average patient has received a proteasome inhibitor and an immunomodulatory inhibitor. And if they had had greater three lines of therapies, they were included, but then if they were refractory to both PI and IMiD, they could be included with two or more prior lines of therapies. And then also allowed, which is interesting with this product, if you’ve had prior BCMA therapy now that we know that BiTEs are available, as well as antibody-drug conjugates or prior CAR-T, that could be enrolled as well.

Now what’s very exciting for patients in the clinic, is that 53 evaluable patients we’re looked at for the presentation, but 16 of those patients actually received their infusion and total therapy as an outpatient. The one other thing that’s very exciting about this study is that there will no longer be production in the old fashion with this product. So they’ll be sticking with the nanoplasmid manufacturing and that will be continued in the dose escalations in a single administration. So right now there’s data looking at the first administration that the 0.75 x 10^6 CAR Ts, and then comparing that with the nanoplasmid compared to the P-BCMA original manufacturing product. And what we’re seeing is that already, we’re selecting those higher T-stem cell memory phenotypes. And that our overall response rate is at 66.7% compared to 50% with the old manufacturing product. And so therefore we’ll be moving the product forward with that manufacturing technique.