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The fully human BCMA-directed CAR T-cell therapy, CT103A, demonstrated deepening efficacy with an acceptable toxicity profile in patients with relapsed or refractory multiple myeloma, according to updated data from the phase 1/2 FUMANBA-1 trial.
The fully human BCMA-directed CAR T-cell therapy, CT103A, demonstrated deepening efficacy with an acceptable toxicity profile in patients with relapsed or refractory multiple myeloma, according to updated data from the phase 1/2 FUMANBA-1 trial (NCT05066646).1
At a median follow-up of 9.0 months, the agent elicited an objective response rate (ORR) of 94.9% in the total patient population evaluable (n = 79), with a very good partial response or better rate of 89.9% and a complete response (CR)/stringent complete response (sCR) rate of 68.4%. The median time to response (TTR) was 16 days (range, 11-123).
Among the 10 patients who had extramedullary myeloma (EMM; n = 10), the ORR with the CAR T-cell therapy was 100%, with a CR or better rate of 90%. Those who previously received a CAR T-cell product (n = 12) also derived benefit from CT103A, although the ORR was not as high, at 75%, with a CR or better rate of 41.7%. In those without EMM who received prior CAR T-cell therapy (n = 61), the ORR with the agent was 98.4%, with a CR or better rate of 70.5%.
“Updated data from the phase 1/2 FUMANBA-1 study continue to show encouraging efficacy of CT103A with a favorable safety profile in relapsed/refractory multiple myeloma,” lead study author Chunrui Li, MD, PhD, of the Department of Hematology at Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, said in a presentation of the data during the 2022 EHA Congress. “CT103A led to a deepening and durable response with robust expansion and prolonged persistence.”
CT103A utilizes a lentiviral vector containing a CAR structure with a fully human single-chain variable fragment, CD8a hinger, and transmembrane, 4-1BB co-stimulatory and CD3ζ activation domains. By leveraging a proprietary in-house optimization platform, the construct of the BCMA-targeted therapy is hypothesized to be strong and durable.
The product was investigated as part of FUMANBA-1, which enrolled those with relapsed or refractory multiple myeloma who had previously received at least 3 therapies, including proteasome inhibitors and immunomodulatory drugs. Patients were required to have experienced disease progression during or within 1 year of their last line of therapy. They also needed to have an ECOG performance status of 0 or 1, and BCMA positivity.
The primary end point of the first phase of the trial was safety and tolerability, and secondary end points included efficacy, pharmacokinetics (PK), and pharmacodynamics (PD). For the second phase of the trial, the primary end point was efficacy in the form of ORR, and secondary end points included safety and tolerability, minimal residual disease (MRD), overall survival, duration of response, TTR, PK, and PD.
Previous data from the phase 1 study, which was conducted at 14 clinical sites throughout China, were shared during the 2021 ASH Annual Meeting and showed that the product was safe and highly active in this patient population.2
As of January 21, 2022, a total of 79 patients had received the CAR T-cell therapy. The median age of these patients at baseline was 57 years (range, 39-70) and 45% were male. The median time since diagnosis was 41.3 months (range, 7.5-193.2).
Moreover, the median number of prior lines of therapy received was 5 (range, 3-23); all patients were double refractory and 16.5% of patients were triple refractory. Notably, 34.2% of patients had high-risk cytogenetics, and 12.7% of patients had EMM. Just under 30%, or 27.8%, of patients previously underwent autologous hematopoietic stem cell transplantation and 15.2% previously received CAR T-cell therapy.
Additional data showed that 92.4% of patients were MRD negative, and all patients who achieved a CR/sCR to treatment were MRD negative. Moreover, the median duration of MRD negativity was not yet reached.
The median progression-free survival in all cohorts except for those who previously received CAR T-cell therapy had not yet been reached. In those with prior CAR T, the median PFS was 7.5 months (95% CI, 2.9–not reached).
When looking at cytokines in the peripheral blood, investigators observed notable expansion, and long persistence. Serum BCMA (sBCMA) was also evaluated in the peripheral blood. sBCMA decreased to the lower limit of qualification (LLOQ) of 3.2 ng/mL at a median of 2 months following the CAR T-cell infusion. Moreover, the sBCMA level remained below the LLOQ at 12 months in those who continued to respond to treatment.
Antidrug antigen (ADA) was detected in 2.6% of the 79 patients at 3 months after infusion; at 6 and 12 months, these rates were 8.2% and 33.3%, respectively. Prior to infusion, ADA was detected in 1.3% of patients. At the median follow-up of 9 months, ADA was detected in 16.5% of patients post-CT103A infusion.
Regarding safety, grade 3 or higher treatment-related adverse effects (AEs) were experienced by 93.7% of patients who received CT103A, the most common of which being neutropenia (82.3%), followed by thrombocytopenia (59.5%), and lymphocytopenia (58.2%). Serious AEs occurred in 69.6% of patients, and included pneumonia (44.3%), thrombocytopenia (21.5%), and enteritis infectious (8.9%).
Any-grade cytokine release syndrome (CRS) was reported in most patients (94.9%); this effect was grade 1 in 73.4% of patients and grade 2 in 21.5% of patients. The median time to onset of CRS was 6 days, and the median duration of days was 5. Immune effector cell–associated neurotoxicity syndrome (ICANS) occurred in 2 patients; these cases were grade 1 and grade 2 in severity.
Previously, in February 2022, the FDA granted an orphan drug designation to CT103A for use as a potential therapeutic option in patients with relapsed or refractory multiple myeloma.3