On December 5, 2018 Janssen Pharmaceuticals of Johnson & Johnson reported the updated results of Legend Biotech Inc.’s LEGEND-2 phase 1/2 open-label study, which evaluated the experimental multi-cell experimental chimeric antigen receptor T ( CAR-T) LCAR-B38M in the treatment of patients with recurrent or refractory advanced multiple myeloma (R / R) (Press release, Johnson & Johnson, DEC 5, 2018, View Source [SID1234531912]). These results, presented in an oral presentation at the 2018 Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) (Abstract # 955 ), 1 based on data from one of the four independent institutional studies of Xi’an Jiaotong Second Affiliated Hospital, which were originally presented at the 2017 Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2 and at the 2017 Annual Congress of the European Association of Hematology (EHA) (Free EHA Whitepaper). 3 These updated results have shown that B-cell maturation antigen-directed (BACM) CAR-T cell-mediated CLAR-B38M therapy has resulted in profound, long-lasting responses with a manageable and tolerable safety profile. in patients who failed a median of three previous treatments. 1

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The science of CAR-T has led to the approval of essential therapeutic interventions for certain blood cancers, and we hope that the results we see for multiple myeloma will provide an additional option so much hoped for by patients," said Dr. Wan-Hong Zhao, Associate Director of Hematology at the Second Affiliated Hospital of Xi’an Jiaotong University in Xi’an, China, and Principal Investigator of the Study We are excited about this data and the fact that they have demonstrated remarkable responses in heavily pretreated patients with multiple myeloma, a population that is traditionally difficult to treat. "

As part of this update of the study, 57 patients with advanced multiple myeloma R / R received cell therapy CAR-T-LCAR B38M. The median age of the patients was 54 (range: 27 to 72 years); the median number of previous treatments was three (range 1-9); and 74% of patients were in stage III of the disease according to the Durie-Salmon classification. 1 The results of the study, the overall response rate was 88% (confidence interval [95% CI]. 76-95 A complete response (CR) was achieved in 74% of patients (95% IC, 60-85), a very good partial response was obtained in 4% of patients (2/57 patients; 95% CI, 0.4 to 12) and a partial response in 11% of patients (95 %, 4-22). 4 It should be noted that of the 42 patients who achieved RC, 39 patients (68%) had negative MRD (minimal residual disease) in the bone marrow as measured by flow cytometry to 8 colors. With a median follow up of 12 months, the median duration of response was 16 months (95% CI: 12 not met [NR]), and a median progression free survival (PFS) 15 months was observed in all patients . In patients with negative MRD, the median PFS was 24 months. 1

The most common adverse events (AEs) were pyrexia (91%), cytokine release syndrome (CRS) (90%), thrombocytopenia (49%) and leukopenia (47%). Grade ≥ 3 adverse events (65%), the most common were leukopenia (30%), thrombocytopenia (23%) and an increase in aspartate aminotransferase (21%). 4 The CRS was mainly grade 1 (47%) and 2 (35%). However, four patients (7%) had a CRS grade 3. The median time to onset of CRS was nine days (range: 1 to 19). All CRS cases except one were resolved within a median of nine days (range: 3-57). Neurotoxicity was observed in one patient who experienced aphasia, agitation, and grade 1 seizure-related activity. A total of 17 patients died during the study and follow-up period; causes of death were progressive disease (ME, n = 14), suicide after EM (n = 1), esophagitis (n = 1), pulmonary embolism and acute coronary syndrome (n = 1) . 1

Janssen has a long-standing commitment to improving outcomes for patients with multiple myeloma, so this early data is encouraging about the potential difference this experimental treatment could make for patients with recurrent or refractory disease. Dr. Catherine Taylor, Head of Hematology Therapy Division, Europe, Middle East and Africa (EMEA) at Janssen-Cilag Limited, will continue to study the safety and efficacy profile of this important BCMA-targeted immunotherapy to understand the potential role it could play as a new approach to treating patients with multiple myeloma. "

In December 2017, Janssen entered into a worldwide collaboration and license agreement with Legend Biotech, USA Inc, and Legend Biotech Ireland Limited ("Legend"), subsidiaries of GenScript Biotech Corporation, to jointly develop and commercialize the LCAR- B38M for the treatment of multiple myeloma. 5 LCAR B38M-CAR is a T-cell therapy directed against two distinct epitopes BCMA, which confers a high avidity and affinity binding of the compound to cells expressing BCMA. 1 In China, a Phase 2 confirmatory trial with the Center for Drug Evaluation (CTR20181007) is being planned to further evaluate LCAR-B38M in patients with advanced R / R multiple myeloma.

While "LCAR-B38M" refers to the experimental product studied in China, the investigational product studied in the United States and the European Union is identified under the reference "JNJ-68284528"; both terms represent the same CAR-T therapy. Janssen and Legend jointly conduct a global Phase 1b / 2 ( NCT03548207 ) trial of JNJ-68284528 to evaluate its efficacy and safety in adults with advanced R / R multiple myeloma. 6 The study is currently recruiting patients following approval by the US Food and Drug Administration of an application for a new investigational drug, as announced in May 2018. 7

About LEGEND-2

LEGEND-2 ( NCT03090659 ) is a single-phase, open – label, one-to-one program implemented in China that includes four independent institutional studies conducted in participating hospitals to evaluate the efficacy and safety of LCAR-B38M in the community. treatment of patients with R / R multiple myeloma. 8

About CAR-T and BCMA

CAR-T cells are an innovative approach to eradicate cancer cells by harnessing the power of the patient’s immune system. BCMA is a protein strongly expressed in myeloma cells. 9 By targeting the BCMA via CAR-T approach, CAR-T therapies could potentially redefine the multiple myeloma treatment paradigm and potentially progress to curative treatments for patients with this disease.

About multiple myeloma

Multiple myeloma (MM) is an incurable blood cancer that originates in the bone marrow and is characterized by excessive proliferation of plasma cells. 10 In 2016, a diagnosis of MM was made in more than 45,000 people in Europe and more than 29,000 patients died. 11 For half of newly diagnosed patients, the survival rate does not exceed five years, 12 and nearly 29% of MM patients die within one year of diagnosis. 13

Although treatment may offer remission, recurrence is unfortunately likely because there is currently no cure. 14 MM is refractory when the disease develops within 60 days of the patient’s last treatment. 15,16 Recurrent cancer is when the disease recurs after a period of initial, partial or complete remission. 17 While some MM patients have no symptoms, most patients are diagnosed with symptoms that may include bone problems, low blood counts, elevated calcium levels, kidney problems, or infections. 18 The prognosis of patients who relapse after treatment with standard therapies, including protease inhibitors and immunomodulatory agents, is poor and there are few treatment options. 19