FHVH-BCMA-T / National Cancer Institute - LARVOL DELTA

Rapid anti-myeloma activity by T cells expressing an anti-BCMA CAR with a human heavy-chain-only antigen-binding domain. (PubMed, Mol Ther) - "The CAR was designated FHVH33-CD8BBZ...Anti-CAR antibody responses were detected in 4/12 patients assessed. FHVH-T have powerful, rapid, and durable anti-MM activity."

IO biomarker • Journal • Hematological Malignancies • Multiple Myeloma • Oncology • CCR7 • CD4

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

BCMA CAR-T-Cell Therapy (ide-cel idecabtagen-vicleucel) in Relapsed and Refractory Multiple Myeloma (RRMM): Results of the Phase 1 Study Support the design of the Phase 3 study KarMMa-3 comparing ide-cel with triplicate combinations standard of care (DGHO 2019) - P1, P2, P3; "Eligible patients have received 2-4 prior regimens, including an IMiD, PI, and daratumumab and are refractory to last therapy... RRMM patients have poor outcomes despite increasing treatments options. The CRB-401 data in patients who received ≥3 prior therapies support investigating ide-cel in earlier treatment lines, as planned in KarMMa-3."

CAR T-Cell Therapy • P1 data • P3 data

T Cells Expressing a Fully-Human Anti-BCMA Chimeric Antigen Receptor with a Heavy-Chain-Only Antigen-Recognition Domain Exhibit Rapid and Durable Activity Against Multiple Myeloma (ASH 2022) - "The CAR containing FHVH33 is called FHVH33-CD8BBZ...Twenty-five patients received 300 mg/m2 of cyclophosphamide and 30 mg/m2 of fludarabine on days -5 to -3 followed by infusion of FHVH-T on day 0...FHVH-T therapy led to durable responses with most anti-myeloma activity occurring within 14 days after FHVH-T infusion. Blood levels of FHVH-T correlated with CD4+CCR7+ infusion cells."

IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • CCR7 • CD8 • CXCL8 • IFNG • IL10 • IL15 • IL2 • IL6

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

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

Treatment of Patients with T Cells Expressing a Fully-Human Anti-BCMA CAR with a Heavy-Chain Antigen-Recognition Domain Caused High Rates of Sustained Complete Responses and Relatively Mild Toxicity (ASH 2021) - "The treatment protocol was 300 mg/m 2 of cyclophosphamide and 30 mg/m 2 of fludarabine on days -5 to -3 followed by infusion of FHVH33-T on day 0...Five patients received tocilizumab and 4 patients received corticosteroids for CRS...Two of the biopsied plasmacytomas were BCMA+, and two were BCMA-negative by immunohistochemistry. FHVH33-CD8BBZ CAR T cells caused relatively mild toxicity and a high rate of sCRs in patients with relapsed MM including MM with low cell-surface BCMA expression."

Clinical • IO biomarker • Hematological Malignancies • Infectious Disease • Inflammation • Multiple Myeloma • Oncology • Plasmacytoma • Pneumonia • Respiratory Diseases • CD8

Early MRD negativity to predict deepening myeloma response in relapsed/refractory multiple myeloma (RRMM) patients treated with bb2121 anti-BCMA CAR T cells. (ASCO 2018) - P1; "bb2121 induced a high frequency of rapid MRD-neg response, independent of IMWG MM responses. These early MRD-neg responses starting at M1 offer insights into bb2121 kinetics and may portend achievement of deeper responses over time."

CAR T-Cell Therapy • Clinical • Multiple Myeloma

bb2121 anti-BCMA CAR T-cell therapy in patients with relapsed/refractory multiple myeloma: Updated results from a multicenter phase I study. (ASCO 2018) - P1; "...In the dose-expansion (Exp) phase, pts had to have received daratumumab and been refractory to last line of therapy; no BCMA expression was required... bb2121 shows promising efficacy at dose levels 150 106 CAR T cells with deep and durable ongoing responses and manageable CRS and NTX. These data support the potential of bb2121 anti-BCMA CAR T cell therapy as a new treatment paradigm for RRMM."

CAR T-Cell Therapy • Clinical • IO biomarker • P1 data • Multiple Myeloma

HIGH BASELINE FERRITIN IS ASSOCIATED WITH GRADE 2 CRS REQUIRING TOCILIZUMAB OR GRADE ≥ 3 CRS IN RELAPSED/REFRACTORY MULTIPLE MYELOMA PATIENTS TREATED WITH BB2121 ANTI-BCMA CAR T CELLS (EHA 2018) - P1; "The overall frequency of tCRS in this study was relatively low and associated with high baseline ferritin. High bone marrow involvement and CAR T cell dose may contribute to the risk."

CAR T-Cell Therapy • Clinical • Multiple Myeloma

EARLY MRD NEGATIVITY PREDICTS DEEPENING MYELOMA RESPONSE IN RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM) PATIENTS TREATED WITH BB2121 ANTI-BCMA CAR T CELLS. (EHA 2018) - "bb2121 induced a high frequency of rapid MRD-negative responses, independent of IMWG MM responses. These early MRD-negative responses starting at M1 offer insights into bb2121 kinetics and may portend achievement of deeper responses."

CAR T-Cell Therapy • Clinical • Multiple Myeloma

BB2121 ANTI-BCMA CAR T CELL THERAPY IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA: UPDATED RESULTS FROM A MULTICENTER PHASE I STUDY (EHA 2018) - P1; "...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... 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."

CAR T-Cell Therapy • Clinical • IO biomarker • P1 data • Multiple Myeloma

Association of high baseline ferritin with tocilizumab administration for CRS in relapsed/refractory multiple myeloma patients treated with bb2121 anti-BCMA CAR T cells. (ASCO 2018) - P1; "The overall frequency of tCRS in this study was relatively low and associated with high baseline ferritin. High BM involvement and CAR T cell dose may contribute to risk."

CAR T-Cell Therapy • Clinical • Multiple Myeloma

T Cells Expressing a Novel Fully-Human Anti-BCMA CAR for Treating Multiple Myeloma (clinicaltrials.gov) - P1; N=31; Active, not recruiting; Sponsor: National Cancer Institute (NCI); Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Hematological Malignancies • Multiple Myeloma • Oncology

Immunotherapy With BCMA CAR-T Cells in Treating Patients With BCMA Positive Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1; N=25; Recruiting; Sponsor: Fred Hutchinson Cancer Research Center; Trial completion date: Dec 2022 ➔ Dec 2037; Trial primary completion date: Dec 2020 ➔ Mar 2022

Clinical • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology • SDC1

BCMA-Specific CAR T-Cells Combined With a Gamma Secretase Inhibitor (JSMD194) to Treat Relapsed or Persistent Multiple Myeloma (clinicaltrials.gov) - P1; N=18; Recruiting; Sponsor: Fred Hutchinson Cancer Research Center; Suspended ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology

Immunotherapy With BCMA CAR-T Cells in Treating Patients With BCMA Positive Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1; N=25; Recruiting; Sponsor: Fred Hutchinson Cancer Research Center; Suspended ➔ Recruiting

Clinical • Enrollment open • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology

Immunotherapy With BCMA CAR-T Cells in Treating Patients With BCMA Positive Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1; N=25; Suspended; Sponsor: Fred Hutchinson Cancer Research Center; Recruiting ➔ Suspended

Clinical • Trial suspension

BCMA-Specific CAR T-Cells Combined With a Gamma Secretase Inhibitor (JSMD194) to Treat Relapsed or Persistent Multiple Myeloma (clinicaltrials.gov) - P1; N=18; Suspended; Sponsor: Fred Hutchinson Cancer Research Center; Recruiting ➔ Suspended

Clinical • Combination therapy • Trial suspension

The B Cell Maturation Antigen (BCMA) Chimeric Antigen Receptor (CAR) T Cell Therapy Idecabtagene Vicleucel (IdeCel; Bb2121) in Relapsed and Refractory Multiple Myeloma (Rrmm): Outcomes from a Phase 1 Study Support the Phase 3 Karmma-3 Study Design to Compare IDE-Cel Versus Standard Triplet Regimens (DKK 2020) - P1, P2, P3; "The CRB-401 phase 1 study (NCT02658929) evaluated ide-cel, a BCMA CAR T-cell therapy, in RRMM patients who received ≥3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or were refractory to both drug classes...Patients will be randomized 2:1 to receive either ide-cel treatment (150–450 × 106 CAR+ T cells) or a standard triplet regimen such as daratumumab, pomalidomide, and dexamethasone (DPd); daratumumab, bortezomib, and dexamethasone (DVd); or ixazomib, lenalidomide, and dexamethasone (IRd); at the investigator’s discretion... Data from CRB-401 in patients with RRMM who received ≥3 prior therapies support investigating ide-cel in earlier treatment lines, as planned in KarMMa-3."

Late-breaking abstract • P1 data • P3 data

Infectious Complications Associated with CAR T-Cell Therapy (ASH 2019) - "Univariate screening methods were used to identify parameters associated with increased risk of infection Amongst 144 subjects, 52 (36.1%) received anti-CD19 CAR T-cells (CAR-T); 53 (36.8%) received anti-CD22 CAR-T, 26 (18.1%) received anti-BCMA CAR-T; and 13 (9%) received anti-GD2 CAR-T. In this retrospective analysis, we provide the largest experience to date analyzing infection in the setting of CAR T-cell therapy across multiple CAR constructs. Our study demonstrates that adult age, prior history of infection, increased number of prior therapies and enrollment on a particular CAR T-cell trial, in this case the CD22 CAR-T trial, may lead to a higher risk of infection than in those without these risk factors. Further investigations are underway to evaluate clinical outcomes with infection which occur in the peri CAR T-cell setting and potential strategies to minimize infection risk."

CAR T-Cell Therapy

Study of T Cells Targeting B-Cell Maturation Antigen for Previously Treated Multiple Myeloma (clinicaltrials.gov) - P1; N=30; Active, not recruiting; Sponsor: National Cancer Institute (NCI); Trial primary completion date: Dec 2018 ➔ Dec 2019

Clinical • Trial primary completion date

Study of T Cells Targeting B-Cell Maturation Antigen for Previously Treated Multiple Myeloma (clinicaltrials.gov) - P1; N=30; Active, not recruiting; Sponsor: National Cancer Institute (NCI); Trial primary completion date: Oct 2019 ➔ Dec 2018

Clinical • Trial primary completion date