On November 4, 2021 Legend Biotech Corporation (NASDAQ: LEGN) (Legend Biotech), a global, clinical-stage biotechnology company developing and manufacturing novel therapies, reported that 12 company-sponsored studies were accepted for presentation at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Press release, Legend Biotech, NOV 4, 2021, View Source [SID1234594523]). These include two oral presentations and 10 poster presentations .
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Presentation highlights include updates from the CARTITUDE clinical development program for the investigational B-cell maturation antigen (BCMA) directed chimeric antigen receptor T cell (CAR-T) therapy, ciltacabtagene autoleucel (cilta-cel), for the treatment of patients with relapsed or refractory multiple myeloma (RRMM). Presentations will detail longer-term follow-up data and new sub-group analysis results from the Phase 1b/2 CARTITUDE-1 study as well as adjusted indirect comparison of CARTITUDE-1 patient outcomes relative to standard-of-care therapies in real-world clinical practice from the LocoMMotion study. First data release from Cohort B and longer-term follow-up data from Cohort A of the CARTITUDE-2 study in earlier lines of treatments will be presented.
Additionally, Legend will share the first preclinical in vivo data on its novel tri-specific single-domain antibody (VHH) CAR-T (LCAR-AIO). LCAR-AIO targets three antigens—CD19, CD20 and CD22—with the potential for development as a treatment for patients with relapsed B cell lymphoma and prior CD19 CAR-T therapies.
"The new and updated data from the CARTITUDE-1 and CARTITUDE-2 studies show that cilta-cel continues to provide early, deep and durable responses, even in high-risk patients," said Ying Huang, PhD, CEO and CFO of Legend Biotech. "What’s also encouraging is the new preclinical data from our novel tri-specific VHH CAR-T, which was designed and developed by Legend. This trispecific CAR-T exemplifies our team’s ability to discover novel mechanisms of action by screening and optimizing antibodies in house."
A select list of abstracts from the meeting can be found below.
ASH Presentations (December 11-14, 2021)
Abstract No.
Title
INFO
Abstract #549
Oral
Updated Results From CARTITUDE-1: Phase 1b/2 Study of Ciltacabtagene Autoleucel, a B-cell Maturation Antigen–Directed Chimeric Antigen Receptor T Cell Therapy, in Patients with Relapsed/Refractory Multiple Myeloma
Session Title: 704. Cellular Immunotherapies: Cellular Therapies for Myeloma
Date/Time: Sunday, December 12, 2021 4:30 PM – 6:00 PM EST
Presentation time: 5:00 PM EST
Room: Georgia World Congress Center, Hall C2-C3
Abstract #550
Oral
Ciltacabtagene Autoleucel for Triple-Class Exposed Multiple Myeloma: Adjusted Comparisons of CARTITUDE-1 Patient Outcomes Versus Therapies from Real-World Clinical Practice from the LocoMMotion Prospective Study
Session Title: 704. Cellular Immunotherapies: Cellular Therapies for Myeloma
Date/Time: Sunday, December 12, 2021 4:30 PM – 6:00 PM EST
Presentation time: 5:15 PM EST
Location: Georgia World Congress Center, Hall C2-C3
Abstract#3938
Poster
Efficacy and Safety of Ciltacabtagene Autoleucel in Patients with Relapsed/Refractory Multiple Myeloma: CARTITUDE-1 Subgroup Analysis
Session Title: 731. Autologous Transplantation: Clinical and Epidemiological: Poster III
Date/Time: Monday, December 13, 2021 6:00 PM – 8:00 PM EST
Location: Georgia World Congress Center, Hall B5
Abstract #2812
Poster
Anakinra Targeting Cytokine Release Syndrome Associated with Chimeric Antigen Receptor T-cell Therapies
Session Title: 704. Cellular Immunotherapies: Clinical: Poster II
Date/Time: Sunday, December 12, 2021 6:00 PM – 8:00 PM EST
Location: Georgia World Congress Center, Hall B5
Abstract #3866
Poster
Efficacy and Safety of Ciltacabtagene Autoleucel (Cilta-cel), a B-cell Maturation Antigen–Directed Chimeric Antigen Receptor T-cell Therapy, in Lenalidomide-Refractory Patients with Progressive Multiple Myeloma After 1–3 Prior Lines of Therapy: Updated
Results From CARTITUDE-2
Session Title: 704. Cellular Immunotherapies: Clinical: Poster III
Date/Time: Monday, December 13, 2021 6:00 PM – 8:00 PM EST
Location: Georgia World Congress Center, Hall B5
Abstract #2910
Poster
CARTITUDE-2: Efficacy and Safety of Ciltacabtagene Autoleucel (Cilta-cel), a B-cell Maturation Antigen (BCMA)-Directed Chimeric Antigen Receptor T Cell (CAR T) Therapy, in Patients with Multiple Myeloma and Early Relapse After Initial Therapy
Session Title: 731. Autologous Transplantation: Clinical and Epidemiological: Poster II
Date/Time: Sunday, December 12, 2021 6:00 PM – 8:00 PM EST
Location: Georgia World Congress Center, Hall B5
Abstract #1835
Poster
Bortezomib, Lenalidomide, and Dexamethasone (VRd) Followed by Ciltacabtagene Autoleucel vs VRd Followed by Lenalidomide and Dexamethasone (Rd) Maintenance in Patients with Newly Diagnosed Multiple Myeloma Not Intended for Transplant: A Randomized, Phase 3 Study (CARTITUDE-5)
Session Title: 731. Autologous Transplantation: Clinical and Epidemiological: Poster I
Date/Time: Saturday, December 11, 2021 5:30 PM – 7:30 PM EST
Location: Georgia World Congress Center, Hall B5
Abstract #3057
Poster
LocoMMotion: A Prospective, Non-interventional, Multinational Study of Real-life Current Standards of Care in Patients with Relapsed/Refractory Multiple Myeloma Who Received ≥3 Prior Lines of Therapy
Session Title: 905. Outcomes Research—Lymphoid Malignancies: Poster II
Date/Time: Sunday, December 12, 2021 6:00 PM – 8:00 PM EST
Location: Georgia World Congress Center, Hall B5
Abstract #1676
Poster
Meta-analysis of Ciltacabtagene Autoleucel versus Physician’s Choice in the Treatment of Patients with Relapsed or Refractory Multiple Myeloma
Session Title: 653. Myeloma and Plasma Cell Dyscrasias: Clinical-Prospective Therapeutic Trials: Poster I
Date/Time: Saturday, December 11, 2021 5:30 PM – 7:30 PM
Location: Georgia World Congress Center, Hall B5
Abstract #4075
Poster
Real-World Outcomes for Standard-Of-Care Treatments in Patients with Relapsed/Refractory Multiple Myeloma
Session Title: 905. Outcomes Research—Lymphoid Malignancies: Poster III
Date/Time: Monday, December 13, 2021 6:00 PM – 8:00 PM EST
Location: Georgia World Congress Center, Hall B5
Abstract #1932
Poster
Considerations for optimal administration of Chimeric Antigen Receptor (CAR) T-Cell therapy programs: a multi-stakeholder qualitative analysis
Session Title: 902. Health Services Research—Lymphoid Malignancies: Poster I
Date/Time: Saturday, December 11, 2021 5:30 PM – 7:30 PM
Location: Georgia World Congress Center, Hall B5
Abstract #1700
Poster
Tri-specific CD19xCD20xCD22 VHH CAR-T cells (LCAR-AIO) eradicate antigen-heterogeneous B cell tumors, enhance expansion, and prolong persistence in preclinical in vivo models
Session Title: 703. Cellular Immunotherapies: Basic and Translational: Poster I
Date: Saturday, December 11, 2021 5:30-7:30 PM
Location: Georgia World Congress Center, Hall B5
About CARTITUDE-1
CARTITUDE-1 (NCT03548207) is a Phase 1b/2, open-label, multicenter study evaluating the safety and efficacy of cilta-cel in adults with relapsed or refractory with multiple myeloma, who previously received a proteasome inhibitor (PI), an immunomodulatory agent (IMiD) and an anti-CD38 antibody, and who had disease progression on or after the last regimen.1 The primary objective of the Phase 1b portion of the study was to characterize the safety and confirm the recommended Phase 2 dose of cilta-cel, informed by the first-in-human study with LCAR-B38M CAR-T cells (LEGEND-2). The Phase 2 portion further evaluated the efficacy of cilta-cel with overall response rate as the primary endpoint. Of the 97 patients enrolled in the trial, 99 percent were refractory to the last line of treatment and 88 percent were triple-class refractory, meaning their cancer did not respond, or no longer responds, to an IMiD, a PI and an anti-CD38 antibody.
About CARTITUDE-2
CARTITUDE-2 (NCT04133636) is an ongoing Phase 2 multicohort study evaluating the safety and efficacy of cilta-cel in various clinical settings. Cohort A included patients who had progressive multiple myeloma after 1–3 prior lines of therapy, including PI and IMiD, were lenalidomide refractory, and had no prior exposure to BCMA-targeting agents. Cohort B included patients with early relapse after initial therapy that included a PI and IMiD. The primary objective was percentage of patients with negative minimal residual disease (MRD).2
About CARTITUDE-5
CARTITUDE-5 (NCT04923893) is a Phase 3 open-label study of bortezomib, lenalidomide, and dexamethasone (VRd) followed by cilta-cel vs. VRd followed by Rd maintenance, in patients with newly diagnosed MM for whom autologous stem cell transplant (ASCT) is not planned as initial therapy.
About LocoMMotion
LocoMMotion (NCT04035226) is a prospective non-interventional study evaluating the safety and efficacy of real-life standard-of-care treatments under routine clinical practice over a 24-month period in patients with RRMM. This study aims to understand the effectiveness of current standards of care in heavily pretreated patients with RRMM (reflecting real-world practice in the patient population progressing after PIs, IMiDs and anti-CD38 antibodies).
About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excessive proliferation of plasma cells.3 Although treatment may result in remission, unfortunately, patients will most likely relapse.4 Relapsed myeloma is when the disease has returned after a period of initial, partial or complete remission and does not meet the definition of being refractory.5 Refractory multiple myeloma is when a patient’s disease is non-responsive or progresses within 60 days of their last therapy.6,7 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections. 8 Patients who relapse after treatment with standard therapies, including protease inhibitors and immunomodulatory agents, have poor prognoses and few treatment options available.9
About Cilta-cel
Cilta-cel is an investigational chimeric antigen receptor T cell (CAR-T) therapy, formerly identified as JNJ-4528 in the U.S. and Europe and LCAR-B38M CAR-T cells in China, that is being studied in a comprehensive clinical development program for the treatment of patients with relapsed or refractory multiple myeloma and in earlier lines of treatment. The design consists of a structurally differentiated CAR-T with two BCMA-targeting single domain antibodies. In December 2017, Legend Biotech, Inc. entered into an exclusive worldwide license and collaboration agreement with Janssen Biotech, Inc. (Janssen) to develop and commercialize cilta-cel. In addition to a Breakthrough Therapy Designation (BTD) granted in the U.S. in December 2019, cilta-cel received a Priority Medicines (PRiME) designation from the European Commission in April 2019, and a BTD in China in August 2020. In addition, Orphan Drug Designation was granted for cilta-cel by the U.S. FDA in February 2019, and by the European Commission in February 2020. A Biologics License Application seeking approval of cilta-cel was submitted to the U.S. FDA and a Marketing Authorization Application was submitted to the European Medicines Agency.