DdBCMA-Targeted CAR-T Therapy Shows Clinical Activity in Multiple Myeloma
Among the 31 patients evaluable for efficacy analysis, ORR was 100%.
CART-ddBCMA, an investigational autologous chimeric antigen receptor (CAR) T-cell therapy which uses a novel synthetic binding domain referred to as a D-Domain to target B-cell maturation antigen (BCMA), has demonstrated clinical activity in a phase 1 study (NCT04155749) for patients with relapsed/refractory multiple myeloma (r/r MM), according to interim data presented at the European Society for Medical Oncology (ESMO) 2022 Congress, September 9-13, 2022 in Paris, France.
Among the 31 patients evaluable for efficacy analysis with a minimum follow-up of 1 month (median 12.1 months), the overall response rate (ORR) was 100%, with 71% of patients achieving a complete response (CR). The CR rate deepened to 75% for patients with a minimum follow-up of 6 months (n=24) and 81% for patients with a minimum follow-up of 12 months (n=16).
“We had a 100% ORR, which was actually pretty remarkable for us and we had patients at time of data cut going on well beyond 27 months, including the very first patient that was treated in the study which was very exciting,” presenter and first author, Matthew Frigault, clinical director, Cellular Immunotherapy Program, BMT & Cellular Therapy, Massachusetts General Hospital, said during his presentation. “We’ve had some patients who were re-treated, who were able to have somewhat stable disease, but did eventually progress, and we did have some patients... with progressive disease.”
As of the May 3, 2022, data cut-off, 31 participants with a median age of 66 years (range: 44-76) had received CART-ddBCMA and were evaluable. The patients had received a median of 5 prior lines of therapy (range 3-16) and 39% (n=12) of these patients had extramedullary disease (EMD). Among the 31 patients evaluable for safety, there were 28 cases of cytokine release syndrome (CRS); however, excepting a single grade 3 case in the second dose level, all cases were grade 2 or lower. Furthermore, there were 7 cases of immune effector cell-associated neurotoxicity syndrome (ICANS), with 2 of these cases being grade 3. Non-CRS/ICANS AEs of grade 3 or grade 4 that occurred after infusion included neutrophil count decreases, anemia, thrombocytopenia, lymphocyte count decreases, febrile neutropenia, white blood cell count decreases, hypertension, cellulitis, hyponatraemia, hypotension, and sepsis.
“I can also say that we have not seen any atypical neurotoxicity, we have not seen any Parkinsons-like syndromes, we have not seen any movement disorders or long-standing tremors in all of the patients that have been treated to date with up to a year of follow-up,” Frigault added during his presentation.
The open-label, multi-center trial is open to patients 18 years of age and older with r/r MM who have been treated with at least 3 prior lines of therapy or who are triple-refractory. Participants receive lymphodepletion at 5 and 3 days before treatment. Patients in dose level 1 received 100x106 CAR T-cells while patients in dose level 2 received 300x106 CAR T-cells. Primary end points include the incidence of treatment-emergent adverse events, including dose limiting toxicities, and the recommended phase 2 dose. Secondary end points include best overall response, ORR, CR rate, duration of response, progression-free survival, and measures of in vivo pharmacokinetics. Firgault mentioned that the investigators have selected dose level 1 (100x106 CAR T-cells) as the recommended phase 2 dose. The study’s estimated completion date is November 1, 2035.
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