Contributions
Abstract: S138
Type: Oral Presentation
Presentation during EHA23: On Friday, June 15, 2018 from 12:30 - 12:45
Location: Room A8
Background
bb2121 is a second-generation chimeric antigen receptor (CAR) T cell therapy targeting B-cell maturation antigen (BCMA) to redirect T cells to recognize and kill malignant myeloma cells. Initial data from the dose-escalation phase of CRB-401, a first-in-human study of bb2121 in relapsed/refractory multiple myeloma (RRMM), have shown promising efficacy and safety.
Aims
Here, we report updated safety and efficacy results on 43 subjects enrolled in this ongoing study.
Methods
CRB-401 (NCT02658929) is a two-part, phase I study of bb2121 in patients with RRMM. Patients in the dose-escalation had received ≥ 3 prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent, or were double refractory, and had ≥ 50% BCMA expression on plasma cells. In the dose-expansion phase, patients had to have received daratumumab and been refractory to their last line of therapy; no BCMA expression was required. Following lymphodepletion with fludarabine (30 mg/m2)/cyclophosphamide (300 mg/m2) given daily for 3 days, patients received 1 infusion of bb2121.
Results
As of 02 Oct 2017, 21 patients had received bb2121 in the 4 dose-escalation cohorts (median follow-up, 35 weeks); no dose-limiting toxicities and no grade ≥ 3 neurotoxicities were observed. Cytokine release syndrome (CRS), primarily grade 1-2, was reported in 15 of 21 (71%) patients; 2 patients had grade ≥ 3 CRS that resolved in 24 hours. There were 2 deaths on study; both patients had achieved complete response (CR) and had not progressed. Overall response rate in the 18 evaluable patients in dose-escalation cohorts ≥ 150 × 106 CAR T cells was 94%; 10 of 18 (56%) patients had CR or unconfirmed CR, and 9 of 10 evaluable patients were minimal residual disease (MRD)-negative. With a median follow-up of 40 weeks in the ≥ 150 × 106 dose-escalation cohorts, median response duration and progression-free survival (PFS) had not been reached; PFS rates at 6 and 9 months were 81% and 71%, respectively. Doses of 150 to 300 × 106 CAR T cells were selected for the expansion phase. Results from an additional 5 months of follow-up and initial data from ~20 patients from the expansion cohort will be presented.
Conclusion
bb2121 shows promising efficacy at dose levels ≥ 150 × 106 CAR T cells with deep and durable ongoing responses and manageable CRS and neurotoxicities. These data support the potential of bb2121 anti-BCMA CAR T cell therapy as a new treatment paradigm for RRMM.
Session topic: 26. Gene therapy, cellular immunotherapy and vaccination - Clinical
Keyword(s): Cancer immunotherapy, Multiple Myeloma, Phase I, Relapse
Abstract: S138
Type: Oral Presentation
Presentation during EHA23: On Friday, June 15, 2018 from 12:30 - 12:45
Location: Room A8
Background
bb2121 is a second-generation chimeric antigen receptor (CAR) T cell therapy targeting B-cell maturation antigen (BCMA) to redirect T cells to recognize and kill malignant myeloma cells. Initial data from the dose-escalation phase of CRB-401, a first-in-human study of bb2121 in relapsed/refractory multiple myeloma (RRMM), have shown promising efficacy and safety.
Aims
Here, we report updated safety and efficacy results on 43 subjects enrolled in this ongoing study.
Methods
CRB-401 (NCT02658929) is a two-part, phase I study of bb2121 in patients with RRMM. Patients in the dose-escalation had received ≥ 3 prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent, or were double refractory, and had ≥ 50% BCMA expression on plasma cells. In the dose-expansion phase, patients had to have received daratumumab and been refractory to their last line of therapy; no BCMA expression was required. Following lymphodepletion with fludarabine (30 mg/m2)/cyclophosphamide (300 mg/m2) given daily for 3 days, patients received 1 infusion of bb2121.
Results
As of 02 Oct 2017, 21 patients had received bb2121 in the 4 dose-escalation cohorts (median follow-up, 35 weeks); no dose-limiting toxicities and no grade ≥ 3 neurotoxicities were observed. Cytokine release syndrome (CRS), primarily grade 1-2, was reported in 15 of 21 (71%) patients; 2 patients had grade ≥ 3 CRS that resolved in 24 hours. There were 2 deaths on study; both patients had achieved complete response (CR) and had not progressed. Overall response rate in the 18 evaluable patients in dose-escalation cohorts ≥ 150 × 106 CAR T cells was 94%; 10 of 18 (56%) patients had CR or unconfirmed CR, and 9 of 10 evaluable patients were minimal residual disease (MRD)-negative. With a median follow-up of 40 weeks in the ≥ 150 × 106 dose-escalation cohorts, median response duration and progression-free survival (PFS) had not been reached; PFS rates at 6 and 9 months were 81% and 71%, respectively. Doses of 150 to 300 × 106 CAR T cells were selected for the expansion phase. Results from an additional 5 months of follow-up and initial data from ~20 patients from the expansion cohort will be presented.
Conclusion
bb2121 shows promising efficacy at dose levels ≥ 150 × 106 CAR T cells with deep and durable ongoing responses and manageable CRS and neurotoxicities. These data support the potential of bb2121 anti-BCMA CAR T cell therapy as a new treatment paradigm for RRMM.
Session topic: 26. Gene therapy, cellular immunotherapy and vaccination - Clinical
Keyword(s): Cancer immunotherapy, Multiple Myeloma, Phase I, Relapse