The first BCMA targeted therapy in the world! The key clinical success of GSK antibody drug conjugate gsk2857916 multiple myeloma is to apply for listing!

December 18, 2019 / Biovalley BIOON / -- British pharmaceutical giant GSK announced recently that the evaluation of B cell mature antigen (BCMA) targeted antibody drug conjugate (ADC) belantamab mafodotin (gsk2857916) single drug treatment for recurrent or refractory multiple myeloma (R / R) Mm) key clinical study dreamm-2 (nct03525678) was published online in the Lancet Oncology Dreamm-2 is a randomized, open label, two arm phase II study involving 196 patients with R / R mm Despite the current standard treatment, these patients' condition worsened, the median number of previous treatment options was 7, and they were difficult to treat with immunomodulatory drugs and proteasome inhibitors, and were difficult to treat and / or intolerant against CD38 antibody In the study, the patients were randomly divided into two groups and received bellantamab mafodotin at a dose of 2.5mg/kg or 3.4mg/kg once every three weeks The results showed that the study reached the main end point: in this group of refractory patients, the overall remission rate (ORR) of bellantamab mafodotin (2.5mg / kg) single drug treatment was 31% (n = 30 / 97), and the data was clinically significant Of the 30 patients with remission, 18 achieved very good partial or better remission, including 3 achieved strict complete remission After a median follow-up of 6 months, the median duration of remission (DOR) and total survival time (OS) were not achieved In this study, the safety and tolerance of belantamab mafodotin were consistent with those observed in dreamm-1, the first human clinical study The most common level 3 or 4 adverse reactions in the 2.5mg/kg group were keratopathy (27%), thrombocytopenia (20%) and anemia (20%) In general, patients in the dreamm-2 study were more severe, with worse prognosis and performance than those in the dreamm-1 study And compared with the dreamm-1 study, patients in the dreamm-2 study had previously received more than one treatment regimen The results of the dreamm-2 study are consistent with those of a similar subset of patients in the dreamm-1 study Based on these data, GSK is in the process of submitting a biological product licensing application (BLA) to the US Food and Drug Administration (FDA) for approval of bellantamab mafodotin 2.5mg/kg dose for prior treatment of patients with recurrent or refractory multiple myeloma (R / RMM) including an immunomodulator, a proteasome inhibitor and an anti-CD38 antibody drug If approved, belantamab mafodotin will become the first anti BCMA drug in the United States Dr Hal Barron, chief scientific officer and President of research and development of GSK, said: "patients with multiple myeloma who accept the currently available treatment but whose disease is still progressing have limited treatment options and poor prognosis Data from the dreamm-2 study show that bellantamab mafodotin can provide these patients with an important new treatment option if approved " The dreamm-1 study and dreamm-2 study are part of the dreamm clinical development project, which includes 10 clinical studies (dreamm-1 to dreamm-10) and is evaluating the efficacy and safety of bellantamab mafodotin as a single drug therapy and as a combination of first-line, second-line and multi-line therapies for mm In March this year, GSK released updated data on the dreamm-1 study, the first human clinical study to evaluate belantamab mafodotin, with the aim of investigating the efficacy and safety of the drug in patients with R / RMM and other BCMA expressing advanced hematological malignancies The results showed that in BCMA positive R / R MM patients, the overall remission rate (ORR) of bellantamab mafodotin was 60% Multiple myeloma (mm) is the second most common hematological malignancy after non-Hodgkin's lymphoma In recent years, although great progress has been made in chemotherapy, proteasome inhibitors, immunomodulator thalidomide derivatives and CD38 targeted antibodies, almost all patients will eventually relapse Therefore, there is an urgent need for new treatment Mm market is close to $14 billion in 2017 and is expected to reach nearly $29 billion in 2027 BCMA is one of the most important biomarkers of B cells, which widely exists on the surface of MM cells In recent years, BCMA has become a very popular target of immunotherapy for mm and other hematological malignancies At present, there are more than 20 immunotherapies developed for BCMA, which are mainly divided into three categories: chimeric antigen receptor T-cell therapy (car-t, represented by new base / Bluebird biology, Novartis), bispecific antibody (BsAb, represented by Amgen), antibody drug conjugate (ADC, represented by GlaxoSmithKline) Belantamab mafodotin is a new type of ADC drug, which is conjugated by a new humanized FC modified anti BCMA monoclonal antibody and a cytotoxic agent MMAF (monthyll auristatin-f) through a non cleaved linker (authorized by drug linkage technology from Seattle Genetics) Belantamab mafodotin targets BCMA on the surface of MM cells by anti BCMA monoclonal antibody, then it is internalized by MM cells, degraded in lysosomes and released non permeable MMAF in MM cells MMAF is a kind of mitotic inhibitor It is an anti tubulin compound It can inhibit cell division by blocking microtubule polymerization, stop tumor cells in g / M phase and induce caspase-3-dependent apoptosis In addition, belantamab mafodotin can induce ADCC mediated by NK cells and ADCP mediated by macrophages Belantamab mafodotin selectively acts on MM cells through a variety of cytotoxic mechanisms, which is expected to provide the next generation of immunotherapy options for this type of cancer At present, belantamab mafodotin is in clinical development for the treatment of R / RMM and other BCMA expressing patients with advanced hematological malignancies In 2017, belantamab mafodotin was awarded breakthrough drug qualification (BTD) by the US FDA and priority drug qualification (prime) by the EU EMA, becoming the first BCMA targeted preparation awarded BTD and prime These qualifications are intended to promote the development of drugs in research that have clinical prospects in areas of major unmet medical needs Original source: pivotal dreamm-2 study demanstrated a clinically meaningful overall response rate with belantamab mafodoin (gsk2857916) for patients with relapsed / recovery multiple myeloma