I’m presenting the results of the phase Ib portion of CARTITUDE-1 which is a study of JNJ-4528 which is an anti-BCMA CAR T therapy for relapsed refractory multiple myeloma. JNJ-4528 is a BCMA directed CAR T but it’s specifically different from other CAR Ts in that it has two BCMA targeting single chain antibodies which are designed to confer avidity. This is the exact same construct that was used in the LEGEND-2 study. The other difference is that the dose of the CAR T here is quite low, the median dose administered was 0.72x106 CAR viable T-cells per kilogram.
We enrolled 29 patients in the phase Ib portion, these were heavily pre-treated patients with median prior lines of therapy of five. 86% were triple refractory. We saw no unexpected safety signals; CRS events were common but only two patients had grade 3 or higher CRS. Interestingly, the median onset to CRS was seven days which is quite later than seen in other BCMA products. Neurotoxicity was infrequent, only one patient had neurotoxicity of grade 3 or higher. Cytopenias were common, as expected, but it was rare to see cytopenias beyond 60 days and patients didn’t really have any unexpected infections to note.
JNJ-4528 was very effective with 100% overall response rate and 86% stringent complete remission rates, 97% greater than or equal to VGPR at a median follow-up of 11.5 months. There were 16 patients in complete remission that were eligible for MRD testing and of those 81% were MRD negative at 10-5 or better and 69% of patients were MRD negative at 10-6. The progression free survival at nine months was 86%.
Based on this data JNJ-4528 has received breakthrough designation by the FDA. The phase II portion has fully enrolled and the phase II/III studies are underway.
What will happen during the next phases of this study?
One of the things that everyone is expecting is durability of these responses. For that you want to wait a little longer but I suspect that at least the phase II portion of this, of CARTITUDE-1 in particular, will be presented in an upcoming meeting soon. Mostly because the FDA has agreed to look at this data sooner rather than later and I think it behoves us to actually put it up there. We may not have the long-term data for the phase II but we will have even a much longer follow-up for these patients.
Because the phase II, this was not a true phase I in the sense that there was no dose escalation. We were just actually testing the dose that was informed by the LEGEND-2 study so even the phase Ib patients all got treated with the same dose as the patients in the phase II. So it will just be an aggregate of all the patients.
The phase II/III studies that are actually starting are more looking at different indications earlier in the course of therapy with myeloma patients, different subsets like high risk patients even up front etc. So those will be completely different studies.
What impact might this study have on clinical practice?
I actually believe that this data is strong enough that JNJ-4528 is a strong candidate to be one of the first BCMA directed CAR Ts approved for multiple myeloma. I believe it will revolutionise the treatment of these patients. There’s a lot of hope out there that these will work.
One of the things I do want to say is that the median onset of seven days to CRS and really any toxicity is very different from the other CAR T products and so the hope here is that maybe this can be given as an outpatient and only admit a small select percentage of patients that have higher grade toxicity. That will open it up to potentially more patients.