CART-ddBCMA, a chimeric antigen receptor (CAR) T-cell therapy, demonstrated durable responses and a 100% overall response rate (ORR) in patients with relapsed/refractory (R/R) multiple myeloma (MM), according to interim results from an ongoing phase I trial.
CART-ddBCMA is an autologous anti-B-cell maturation antigen (BCMA) CAR T-cell therapy that uses a novel, synthetic binding domain, called a D-Domain, instead of a typical single-chain variable fragment (scFv) binder.
Matthew Frigault, MD, of the Cancer Center at Massachusetts General Hospital in Boston, shared the results at the 2022 European Society for Medical Oncology Congress.
The phase I, multicenter, open-label, dose-escalation trial enrolled 31 patients (median age, 66 years; range, 44-76 years) who had received at least three prior lines of therapy (median, 5 therapies; range, 3-16 therapies) or were triple-refractory for MM.
The patients were given lymphodepletion on days ‒5, ‒4, and ‒3 followed by infusion of CART-ddBCMA on day zero. Among the 31 patients, 25 received dose level one (DL1; 100×106 CAR+T cells) and six patients received DL2 (300×106 CAR+T cells).
Patients in the trial had a high tumor burden, with 39% having extramedullary disease (EMD) at the start of the trial. “This is actually one of biggest predictor factors for poor outcomes, with the median [progression-free survival] of CARTITUDE-1 patients, who actually manage their disease, being only 12 months,” Dr. Frigault said.
The interim results showed that patients’ responses to CART-ddBCMA deepened over time, Dr. Frigault said (see TABLE 1).
|TABLE 1. Patients’ Responses to CART-ddBCMA in Ongoing Phase I Trial|
|Minimum follow-up||1 month||6 months||12 months|
|Patients with EMD||12 (39%)||12 (50%)||8 (50%)|
|Complete response rate||22 (71%)||18 (75%)||13 (81%)|
“We had 100% [ORR], which was actually pretty remarkable for us,” Dr. Frigault said. “We have patients at time of [data cutoff] going on well beyond 27 months, including the very first patient that was treated on the study, which is very exciting.”
In terms of adverse events, Dr. Frigault highlighted the following:
- No tissue-related toxicity
- One case of grade 3 immune effector cell-associated neurotoxicity syndrome event at DL2
- No cases of grade ≥3 cytokine release syndrome
- No delayed neurotoxicity or Parkinson-like events to date
A phase II trial is expected to begin this year using the dose escalation from phase I, Dr. Frigault said.
CART-ddBCMA has been granted Fast Track, Orphan Drug, and Regenerative Medicine Advanced Therapy designations by the U.S. Food and Drug Administration, according to a statement issued from the manufacturer of the drug.
This study was funded by Arcellx.
Frigault M, Rosenblatt J, Raje N, et al. CART-ddBCMA for multiple myeloma: interim results from phase I study. Abstract #620O. Presented at the 2022 European Society for Medical Oncology (ESMO) Congress, September 9-13, 2022.