Contributions
Abstract: S142
Type: Oral Presentation
Presentation during EHA22: On Friday, June 23, 2017 from 11:45 - 12:00
Location: Room N109
Background
To test the safety and efficacy of the CAR T cell modality in relapsed/refractory multiple myeloma (MM), we have designed a second-generation CAR construct targeting B cell maturation antigen (BCMA) to redirect T cells to MM. bb2121 consists of autologous T cells transduced with a lentiviral vector encoding a novel CAR incorporating an anti-BCMA scFv, a 4-1BB costimulatory motif and a CD3-zeta T cell activation domain. We will report updated safety and efficacy results following promising initial results (Berdeja et al, ENA 2016).
Aims
The primary objective is to determine the maximally tolerated dose of bb2121 in subjects with MM whose tumors express BCMA, to determine and test a recommended phase 2 dose for future studies. The secondary objective is to provide preliminary efficacy data on the anti-tumor effects of treatment with bb2121 in subjects with MM whose tumors express BCMA.
Methods
CRB-401 (NCT02658929) is a multi-center phase 1 dose escalation trial of bb2121 in patients with relapsed and/or refractory MM who have received ≥ 3 prior regimens, including a proteasome inhibitor and an immunomodulatory agent, or are double-refractory, and have ≥ 50% BCMA expression on plasma cells. Peripheral blood mononuclear cells are collected via leukapheresis. Patients undergo lymphodepletion with Flu (30 mg/m2) Cy (300 mg/m2) daily for 3 days then receive 1 infusion of bb2121. The study follows a standard 3+3 design with planned dose levels of 5.0, 15.0, 45.0, 80.0 and 120 x 107 CAR+ T cells.
Results
As of November 18, 2016, 11 patients had been infused with bb2121 in the first 4 dose cohorts, and 9 patients had reached at least 1 month of follow-up. As of data cut-off, no dose limiting toxicities, and no >Grade 2 neurotoxicities or cytokine release syndrome (CRS) had been observed. Grade 1-2 CRS has been reported in 8/11 (73%) treated patients. All patients treated with doses of 15.0 x 107 or higher remained on study and the overall response rate (ORR) in the 9 evaluable patients is 100%, including 2 sCRs and 2 MRD-negative responses (sCR and VGPR). CAR+ T cell expansion has been demonstrated consistently. An additional 6 months of follow up on reported results and initial data from an additional ~10 patients will be presented.
Conclusion
bb2121 shows promising efficacy at dose levels above 5.0 x 107 CAR+ T cells, including 2 sCRs and ongoing clinical responses at 6 months with mild and manageable CRS to date. These initial data support the potential of CAR T therapy with bb2121 as a new treatment paradigm in MM.
Session topic: 24. Gene therapy, cellular immunotherapy and vaccination
Keyword(s): Multiple Myeloma, Immunotherapy
Abstract: S142
Type: Oral Presentation
Presentation during EHA22: On Friday, June 23, 2017 from 11:45 - 12:00
Location: Room N109
Background
To test the safety and efficacy of the CAR T cell modality in relapsed/refractory multiple myeloma (MM), we have designed a second-generation CAR construct targeting B cell maturation antigen (BCMA) to redirect T cells to MM. bb2121 consists of autologous T cells transduced with a lentiviral vector encoding a novel CAR incorporating an anti-BCMA scFv, a 4-1BB costimulatory motif and a CD3-zeta T cell activation domain. We will report updated safety and efficacy results following promising initial results (Berdeja et al, ENA 2016).
Aims
The primary objective is to determine the maximally tolerated dose of bb2121 in subjects with MM whose tumors express BCMA, to determine and test a recommended phase 2 dose for future studies. The secondary objective is to provide preliminary efficacy data on the anti-tumor effects of treatment with bb2121 in subjects with MM whose tumors express BCMA.
Methods
CRB-401 (NCT02658929) is a multi-center phase 1 dose escalation trial of bb2121 in patients with relapsed and/or refractory MM who have received ≥ 3 prior regimens, including a proteasome inhibitor and an immunomodulatory agent, or are double-refractory, and have ≥ 50% BCMA expression on plasma cells. Peripheral blood mononuclear cells are collected via leukapheresis. Patients undergo lymphodepletion with Flu (30 mg/m2) Cy (300 mg/m2) daily for 3 days then receive 1 infusion of bb2121. The study follows a standard 3+3 design with planned dose levels of 5.0, 15.0, 45.0, 80.0 and 120 x 107 CAR+ T cells.
Results
As of November 18, 2016, 11 patients had been infused with bb2121 in the first 4 dose cohorts, and 9 patients had reached at least 1 month of follow-up. As of data cut-off, no dose limiting toxicities, and no >Grade 2 neurotoxicities or cytokine release syndrome (CRS) had been observed. Grade 1-2 CRS has been reported in 8/11 (73%) treated patients. All patients treated with doses of 15.0 x 107 or higher remained on study and the overall response rate (ORR) in the 9 evaluable patients is 100%, including 2 sCRs and 2 MRD-negative responses (sCR and VGPR). CAR+ T cell expansion has been demonstrated consistently. An additional 6 months of follow up on reported results and initial data from an additional ~10 patients will be presented.
Conclusion
bb2121 shows promising efficacy at dose levels above 5.0 x 107 CAR+ T cells, including 2 sCRs and ongoing clinical responses at 6 months with mild and manageable CRS to date. These initial data support the potential of CAR T therapy with bb2121 as a new treatment paradigm in MM.
Session topic: 24. Gene therapy, cellular immunotherapy and vaccination
Keyword(s): Multiple Myeloma, Immunotherapy