bb21217 / BMS, Regeneron - LARVOL DELTA

Researchers at John Theurer Cancer Center, a member of the Georgetown Lombardi Comprehensive Cancer Center Consortium, participated in 46 studies presented at the 2019 American Society of Hematology’s Annual Meeting & Exposition (PRNewswire) - P2, N=105; ZUMA-2 (NCT02601313); Sponsor: Kite, A Gilead Company; P1, N=74; NCT03274219; Sponsor: bluebird bio; P3, N=200; ASCERTAIN (NCT03306264); Sponsor: Astex; "Experts at Hackensack Meridian Health John Theurer Cancer Center...participated in 46 studies presented over the last week at the American Society of Hematology's (ASH) 61st Annual Meeting & Exposition, held at the Orange County Convention Center in Orlando, FL from December 7-10."

P1 data • P2 data • P3 data • Cytomegalovirus Infection • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Mantle Cell Lymphoma • Multiple Myeloma • Myelodysplastic Syndrome • Oncology

CRB-402: Study of bb21217 in Multiple Myeloma (clinicaltrials.gov) - P1 | N=72 | Completed | Sponsor: 2seventy bio | Active, not recruiting ➔ Completed | Trial completion date: Oct 2025 ➔ Dec 2022 | Trial primary completion date: Oct 2025 ➔ Dec 2022

CAR T-Cell Therapy • Trial completion • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

[VIRTUAL] Relapsed/Refractory (R/R) MM (ASCO 2021) - "Results from the Phase III BOSTON trial evaluating selinexor in combination with bortezomib and dexamethasone; clinical implications Key efficacy and safety findings supporting the FDA approval of daratumumab in combination with carfilzomib and dexamethasone for patients with R/R MM (CANDOR and EQUULEUS trials) Mechanism of action of isatuximab; structural and pharmacologic similarities and differences between isatuximab and daratumumab and the implications, if any, for activity and tolerability Design, eligibility criteria and key efficacy and safety findings from the Phase III ICARIA-MM and IKEMA trials; FDA-approved indication for isatuximab and current and potential clinical role Mechanism of action of belantamab mafodotin and efficacy and safety results from the Phase II DREAMM-2 study evaluating that agent for R/R MM; preliminary findings from DREAMM-6 evaluating belantamab mafodotin in combination with bortezomib/dexamethasone FDA approval of belantamab mafodotin..."

IO biomarker • BCL2

[VIRTUAL] BCMA-Directed CAR T-Cells: Early Results and Future Directions (SOHO 2021) - "Other Constructs of Interest Orva-cel (orvacabtagene autoleucel) is an anti-BCMA CAR T product with a construct containing a fully human scFv, an optimized spacer, a 4-1BB co-stimulatory domain, and a CD3z activation domain...Bb21217 has an identical construct to ide-cel except for coculturing with the phosphoinositide 3 kinase inhibitor (PI3K) bb007 during ex vivo culture to enrich for T cells displaying a memory-like phenotype...The ORR was 94%.17 P-BCMA-101 is a novel construct using an anti-BCMA Centyrin™ fused to a 4-1BB costimulatory domain and CD3z signaling domain...Both ide-cel and cilta-cel are being evaluated in various patient populations, including early-relapse and newly diagnosed high-risk patients...The first results of an allogeneic BCMA-directed CAR-T was with ALLO-715. The initial results from the UNIVERSAL phase 1 study in RRMM are encouraging, with responses reported and more attenuated toxicity.26 Others, including CTX120, BCMAUCART, UCART CS1, and..."

CAR T-Cell Therapy • Hematological Malignancies • Multiple Myeloma • Oncology • CD19 • CD4 • CD8 • SDC1 • TNFA

FIRST-IN-HUMAN MULTICENTER STUDY OF BB2121 ANTI-BCMA CAR T CELL THERAPY FOR RELAPSED/REFRACTORY MULTIPLE MYELOMA: UPDATED RESULTS (EHA 2017) - P1; "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."

CAR T-Cell Therapy • Clinical • Biosimilar • Multiple Myeloma

[VIRTUAL] Multiple Myeloma (MM) (ASCO 2021) - "Biologic rationale for targeting the B-cell maturation antigen (BCMA) with CAR T-cell therapy for MM Compositional and mechanistic similarities and differences among various BCMA-targeted CAR T-cell platforms under investigation for MM Design, eligibility criteria and available efficacy and safety results from the pivotal Phase II KarMMa trial of idecabtagene vicleucel for patients with R/R MM; recent FDA approval and optimal integration into treatment algorithms Clinical, biologic and pathologic factors in the selection of patients with MM for treatment with CAR T-cell therapy Updated results from the CARTITUDE-1, EVOLVE and CRB-402 trials of ciltacabtagene autoleucel, orvacabtagene autoleucel and bb21217, respectively, for patients with R/R MM Incidence, timing and severity of adverse events associated with BCMA-directed CAR T-cell therapies for MM; optimal monitoring and management strategies Other promising CAR T-cell platforms under investigation in MM (eg,..."

Hematological Malignancies • Multiple Myeloma • Oncology

[VIRTUAL] Molecular and Phenotypic Profiling of Drug Product and Post-Infusion Samples from CRB-402, an Ongoing: Phase I Clinical Study of bb21217 a BCMA-Directed CAR T Cell Therapy (ASH 2020) - P1 | "bb21217 is a BCMA-directed chimeric antigen receptor (CAR) T cell therapy that uses the same CAR molecule as idecabtagene vicleucel (ide-cel, bb2121), but adds the PI3K inhibitor bb007 during manufacturing to enrich the drug product (DP) for memory-like T cells, thereby reducing the proportion of highly differentiated or senescent T cells. As seen with other CAR T cell studies, the quality of incoming PBMCs, in particular the fraction of T cells with a late differentiation/senescent phenotype, influences initial and sustained clinical response. The analyses reported here support the mechanistic hypothesis of bb21217, suggesting the presence of early memory like T cells in PBMC and/or DP may contribute to high peak expansion and prolonged DOR, while presence of highly differentiated or senescent T cells may negatively impact these measures. Further clinical evaluation of bb21217 and robust correlative analyses will be important to help contextualize the influence of..."

CAR T-Cell Therapy • Clinical • IO Biomarker • P1 data • Hematological Malignancies • Multiple Myeloma • Oncology • CD27 • CD38 • CD57 • GZMA • GZMB • IRF4

Updated Clinical and Correlative Results from the Phase I CRB-402 Study of the BCMA-Targeted CAR T Cell Therapy bb21217 in Patients with Relapsed and Refractory Multiple Myeloma (ASH 2021) - P1 | "Introduction: Idecabtagene vicleucel (ide-cel, bb2121) is the first chimeric antigen receptor (CAR) T cell therapy approved for the treatment of relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody...Patients underwent lymphodepletion with fludarabine (30 mg/m 2 ) and cyclophosphamide (300 mg/m 2 ) daily for 3 days, then received a single infusion of bb21217 at 150, 300 or 450 x 10 6 CAR+ T cells...Median time to first onset of CRS was 2 days (1-20); tocilizumab (38 pts) + corticosteroids (12 pts) was used to manage CRS... Adverse events are consistent with known toxicities of CAR T cell therapies. Efficacy results are encouraging with a median DOR estimate of 17M, CR rate continues to mature. Patients with higher levels of proliferative, less differentiated memory like CAR+ T cells at peak expansion are more likely to experience prolonged..."

CAR T-Cell Therapy • Clinical • IO biomarker • P1 data • Hematological Malignancies • Immune Modulation • Immunology • Inflammation • Multiple Myeloma • Oncology • CD27 • CD28 • CD8

Durable Clinical Responses in Heavily Pretreated Patients with Relapsed/Refractory Multiple Myeloma: Updated Results from a Multicenter Study of bb2121 Anti-Bcma CAR T Cell Therapy (ASH 2017) - P1; "...Cytokine release syndrome (CRS), primarily Grade 1 or 2, was reported in 15 of 21 (71%) patients: 2 patients had Grade 3 CRS that resolved in 24 hours and 4 patients received tocilizumab, 1 with steroids, to manage CRS... bb2121 shows promising efficacy at dose levels above 50 x 106 CAR+ T cells, with manageable CRS and no DLTs to date. ORR was 100% at these dose levels with 8 ongoing clinical responses at 6 months and 1 patient demonstrating a sustained response beyond one year. These initial data support the potential of CAR T therapy with bb2121 as a new treatment paradigm in RRMM."

CAR T-Cell Therapy • Clinical • Biosimilar • Inflammation • Leukemia • Multiple Myeloma

Updated clinical and correlative results from the Phase I CRB-402 study of the BCMA-targeted CAR T cell therapy bb21217 in patients with relapsed and/or refractory multiple myeloma (IMW 2022) - P1 | "Introduction: bb21217 is a B-cell maturation antigen (BCMA) directed chimeric antigen receptor (CAR) T cell therapy which uses the same CAR molecule as ide-cel, the first CAR T cell therapy approved for the treatment of relapsed or refractory multiple myeloma (RRMM). bb21217 treatment resulted in deep durable responses. Low baseline tumor burden, low baseline inflammation, high memory like/proliferative phenotype and low exhaustion/senescence markers in PBMC and DP were associated with positive clinical outcomes."

CAR T-Cell Therapy • Clinical • IO biomarker • P1 data • Hematological Malignancies • Immune Modulation • Immunology • Inflammation • Multiple Myeloma • Oncology • B3GAT1 • CD4 • HAVCR2 • LAG3 • PD-1

First-in-human multicenter study of bb2121 anti-BCMA CAR T-cell therapy for relapsed/refractory multiple myeloma: Updated results. (ASCO 2017) - P1; "bb2121 shows promising efficacy at dose levels above 5 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. Study sponsored by bluebird bio."

CAR T-Cell Therapy • Clinical • Biosimilar • Multiple Myeloma

Dr. Raje on the Utilization of bb21217 in Relapsed/ Refractory Multiple Myeloma (OncLive) - "Noopur Raje, MD...discusses the utilization of bb21217 in patients with relapsed/refractory in multiple myeloma....Regarding toxicity, no new safety signals were seen, though central nervous system toxicity was observed at grades 1 and 2, Raje continues. These toxicity findings were similar to findings reported with the use of idecabtagene vicleucel (ide-cel; Abecma) and ciltacabtagene autoleucel (cilta-cel; Carvykti), Raje concludes."

Video

Early Time-to-Tocilizumab after B Cell Maturation Antigen-Directed Chimeric Antigen Receptor T Cell Therapy in Myeloma. (PubMed, Transplant Cell Ther) - "We retrospectively analyzed our institution's experience with 4 BCMA-directed CAR-T therapies (idecabtagene vicleucel, bb21217, ciltacabtagene autoleucel, and orvacabtagene autoceucel) for RRMM over a 3-year period ending in June 2020. However, total CRS duration may be shorter with early-toci workflows. Prospective validation of our findings may lead to improved safety and cost-effectiveness profiles for CAR-T therapy in RRMM."

CAR T-Cell Therapy • IO biomarker • Journal • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Current state and next-generation CAR-T cells in multiple myeloma. (PubMed, Blood Rev) - "Here, we review the main clinical trials of CAR-T cells in MM with the most advanced autologous BCMA-directed ide-cel and cilta-cel, the human CARs orva-cel and CT053, the alternative manufacturing process with P-BCMA-101 and bb21217, the dual CAR GC012F and the allogenic BCMA-directed CAR-T cells ALLO-715. In light of those clinical data, we provide an overview of CAR-T cells' main potential resistance mechanisms, including antigen loss, antigen spreading, anti-CAR antibodies, CAR-T cell exhaustion, and the emergence of a non-permissive microenvironment. Finally, we describe the principal area of research to build the next generation of CAR-T cells, with armored-, gated- or commuting-CARs, CARs associated with knock out of specific genes, and CAR-T cells made from γδT cells or NK cells."

CAR T-Cell Therapy • Journal • Review • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology

Noopur Raje on bb21217 in Myeloma (YouTube) - "Noopur Raje, MD...describes the new BCMA-targeting CAR T-cell therapy bb21217 and how it differs from idecabtagene vicleucel, the recently FDA-approved CAR T-cell therapy for myeloma."

Video

"No further development of bb21217. Abecma (ide-cel) only. https://t.co/CjZV5XHV8M" (@PLMcCarthyMD)

"I last wrote about the "Goldilocks Car", bb21217, in 2020. $TSVT discontinued it today, and the story suggests why $BLUE" (@JacobPlieth)

2seventy bio Shares Key Milestones and Business Updates for 2022 (Businesswire) - "Based on the strength of the ABECMA clinical data and high commercial interest, 2seventy bio and BMS do not plan to pursue further development of bb21217."

Discontinued • Hematological Malignancies • Multiple Myeloma • Oncology

The Future of BCMA-Targeting in Myeloma (YouTube) - "Noopur Raje, MD...looks into the future of BCMA-targeting CAR T-cell therapies such as bb21217 and how this class of agents will fit in the myeloma treatment landscape."

Video

Phase I study of bb21217 CAR-T therapy in R/R myeloma (YouTube) - P1, N=NA; (NCT03274219); Sponsor: bluebird bio; "Noopur Raje, MD...shares the latest findings from a large Phase I study (NCT03274219) of bb21217, a BCMA-directed CAR T-cell therapy, in patients with relapsed/refractory (R/R) multiple myeloma. Unlike previous BCMA-targeting CAR-T agents, bb21217 is exposed to a PI3K inhibitor during ex vivo culture to enrich the product for a memory-like T-cell phenotype. In total, 72 patients were treated at three dose levels of bb21217, up to the target dose of 450 x 10^6 CAR+ T-cells. The overall response rate across the three groups was 69%. CAR+ T-cells could be detected at 6 months and 12 months in 81% and 60% of patients, respectively. Additionally, a greater number of CD8+ CAR+ T-cells expressing CD27 and CD28 at baseline was associated with a longer duration of response. Overall, these findings support the rationale that enrichment for memory-like T-cells is associated with prolonged efficacy."

Interview • P1 data • Video

2seventy bio Presents Data Across Multiple Cell Therapy Programs at ASH 2021 Annual Meeting (Businesswire) - P1, N=72; NCT03274219; Sponsor: bluebird bio; "New follow-up data from the Phase 1 study demonstrate the enrichment of bb21217 drug product for memory-like markers at or around peak CAR+ T cell expansion may be associated with sustained response. For all patients treated (n=72), the overall response rate was 69%, with 36% having a complete response. The median duration of response was 23.8 (16.8-34.2) months for all patients and 34.8 (17.0-NE) months for patients with a complete response. CAR+ T cells persisted long-term, with 16/21 evaluable patients at Month 12 and 6/8 evaluable patients at Month 24 having CAR+ T cells detectable by molecular technique across doses."

P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

Research Shows Promising Efficacy of bb21217 in Relapsed/Refractory Myeloma - "In a phase I trial, the B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T-cell therapy bb21217 demonstrated 'encouraging' efficacy in patients with relapsed/refractory multiple myeloma, with adverse events (AEs) consistent with other CAR T-cell therapies. Updates from this trial were presented at the 63rd American Society of Hematology (ASH) Annual Meeting & Exhibition by Noopur Raje, MD."

Media quote

"Bb21217 Update -Safety CRS ICANS #ASH21 #MMSM #HealthTreeMM" (@MyelomaTeacher)

Clinical • Hematological Malignancies • Multiple Myeloma

2seventy bio Reports Third Quarter Financial Results and Recent Operational Progress (Businesswire) - "UPCOMING ANTICIPATED MILESTONES: (i) Acceptance of investigational new drug (IND) application for bbT369 in bNHL by the end of 2021; (ii) Presentation of new preclinical data from the SC-DARIC33 program at the 63rd ASH Annual Meeting in December 2021; (iii) Presentation of clinical data from the ongoing CRB-402 study of bb21217 at the 63rd ASH Annual Meeting in December 2021."

IND • P1 data • Preclinical • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

2seventy bio Completes Spin Transaction and Launches Innovative Immuno-oncology Cell Therapy Company (Businesswire) - "2seventy bio...announced its official launch as an independent, publicly traded company. 2seventy bio will trade on the Nasdaq Global Select Market, commencing tomorrow, November 5 under the ticker symbol 'TSVT'....The company officially separates today from bluebird bio, Inc. and launches with a robust cell therapy pipeline across a range of hematologic and solid tumors including two candidates that are planned to enter the clinic in the first half of 2022. The portfolio also includes a development and 50/50 U.S. commercialization partnership with Bristol Myers Squibb (BMS) for ABECMA..."

Commercial • Hematological Malignancies • Multiple Myeloma • Oncology