GSK's BCMA-Targeted Antibody-Drug Conjugate Belantamab Mafodotin (GSK2857916) Achieves Success in Pivotal Trial for Relapsed/Refractory Multiple Myeloma, Aiming for Regulatory Submission by Year-End

August 24, 2019 News /BioValleyBIOON/ -- UK pharmaceutical giantGlaxoSmithKline(GSK) recently announced positive topline data from the pivotal DREAMM-2 clinical study (NCT03525678) evaluating belantamab mafodotin (GSK2857916), a B-cell maturation antigen (BCMA)-targeted antibody-drug conjugate (ADC), for the treatment of relapsed or refractory multiple myeloma (R/R MM). These data will form the basis for regulatory submissions to be initiated later this year.

DREAMM-2 was a randomized, open-label study that enrolled 196 patients with relapsed/refractory multiple myeloma (R/R MM) who were refractory to immunomodulatory agents and proteasome inhibitors and had previously failed anti-CD38 antibody therapy. The results demonstrated that the study met its primary endpoint: belantamab mafodotin showed a clinically meaningful overall response rate in this refractory patient population. The safety and tolerability profile of belantamab mafodotin in this study was consistent with that observed in the first-in-human clinical study, DREAMM-1.

The complete data of the study will be presented at the upcoming medicalMeetingpublished. Dr. Hal Barron, Chief Scientific Officer and President of Research and Development at GSK, stated: “I am pleased with the results from the DREAMM-2 study, as these data hold significant implications for patients with multiple myeloma who have failed current therapies. We will submit the regulatory application for belantamab mafodotin later this year and continue to explore the potential of this medication to help more patients.”

The DREAMM-1 and DREAMM-2 studies are part of the DREAMM clinical development program, which comprises 10 clinical trials (DREAMM-1 through DREAMM-10) evaluating the efficacy and safety of belantamab mafodotin as monotherapy and in combination regimens for first-line, second-line, and later-line treatment of multiple myeloma (MM).

In March this year, GSK announced updated data from the DREAMM-1 study, which is the first human clinical study evaluating belantamab mafodotin. The purpose of the study was to investigate the drug in R/R MM and other advanced hematologic malignancies expressing BCMA.TumorEfficacy and Safety in Patients. The results showed that the overall response rate (ORR) of belantamab mafodotin treatment reached 60% in BCMA-positive R/R MM patients.

Multiple myeloma (MM) is the second most common hematologic malignancy, after non-Hodgkin lymphoma.Tumor. In recent years, despite significant advances in chemotherapy, proteasome inhibitors, immunomodulatory thalidomide derivatives, and CD38-targeted antibodies, nearly all patients eventually experience relapse. Therefore, there is an urgent need for new therapeutic regimens. The multiple myeloma (MM) market was valued at nearly $14 billion in 2017 and is projected to reach approximately $29 billion by 2027.

BCMA is an extremely important B cellBiomarker, widely expressed on the surface of MM cells, has become a target in MM and other hematologic malignanciesTumora highly popular target for immunotherapy. Currently, there are more than 20 immunotherapies developed against BCMA, primarily divided into three categories: chimeric antigen receptor T-cell therapy (CAR-T, Celgene/Bluebird Bio,Novartisas a representative), bispecific antibodies (BsAbs, represented by Amgen), antibody-drug conjugates (ADCs,GlaxoSmithKlineas a representative).

Belantamab mafodotin is a novel humanized, Fc-engineered anti-BCMA monoclonal antibody conjugated to the cytotoxic agent MMAF (monomethyl auristatin-F) via a non-cleavable linker (drug-linker technology from SeattleGenetics(an ADC drug formed by conjugation upon obtaining authorization). Belantamab mafodotin targets and binds to BCMA on the surface of multiple myeloma (MM) cells via an anti-BCMA monoclonal antibody, is rapidly internalized by MM cells, degraded in lysosomes, and releases non-permeable MMAF intracellularly to exert its therapeutic effect. MMAF is a mitotic inhibitor and an anti-tubulin agent that suppresses cell division by blocking microtubule polymerization, thereby enablingTumorCells arrest in the G₂/M phase and induce caspase-3-dependentApoptosis。

Furthermore, belantamab mafodotin can induce NK cell-mediated ADCC (antibody-dependent cellular cytotoxicity) and simultaneously induce macrophage-mediated ADCP (antibody-dependent cellular phagocytosis). By selectively targeting MM cells through multiple cytotoxic mechanisms, belantamab mafodotin holds promise as a highly potential next-generation immunotherapy option for this type of cancer.

Currently, belantamab mafodotin is in clinical development for the treatment of relapsed/refractory multiple myeloma (R/R MM) and other advanced hematologic malignancies expressing BCMA.TumorTreatment of patients. In 2017, belantamab mafodotin received U.S.FDAGranted Breakthrough Therapy Designation (BTD) and Priority Medicines (PRIME) designation by the European Medicines Agency (EMA), becoming the first BCMA-targeted therapy to receive both BTD and PRIME designations. These designations aim to facilitate the development of investigational drugs with clinical potential in areas of significant unmet medical needs. (Bioon.com)

Original Source:GlaxoSmithKline PLC.