GSK reaches endpoint in pivotal blood cancer study

Belantamab mafodotin is an immuno-conjugate comprising a humanised anti-B cell maturation antigen (BCMA) monoclonal antibody conjugated to the cytotoxic agent auristatin F via non-cleavable linker. Albeit GSK did not present detailed data, its announcement suggest that the bispecific fusion protein may offer an alternative treatment regime in multiple myeloma, which normally becomes refractory after a short period of treatment.

In the ongoing open-label, randomised Phase II study on 196 patients with either a relapse or resistance to an immunomodulatory drug such as lenalidomide or pomalidomide, a proteasome inhibitor such as bortezomib, ixazomib or carfilzomib, and an anti-CD38 antibody, i.e. daratumumab, belantamab mafodotin met its primary objective and demonstrated a clinically meaningful overall response rate with belantamab mafodotin in the patient population. The safety and tolerability profile was consistent with that observed in DREAMM-1, the Phase I study of belantamab mafodotin.

GSK expects to submit market approval application for the ADC by year end. However, the drug has to prove its clinical utility versus several CAR T therapies also targeting BCMA, which had previously shown ORRs ranging from 80% to 100%. The most advanced CAR-T candidate bb2121 is developed by bluebird bio Inc. and partner Celgene Inc., the latter having also a Phase I/II candidate in testing. Competition is huge as there are 3 further ADCs, 5 bispecific antibodies, and 5 further CAR-T cell therapies targeting multiple myeloma in Phase I/II stage.

In previous studies belantamab mafodotin provided an ORR of abou 60%. In a press release, GSK announced it will launch six more DREAMM trials. The normal function of BCMA is to promote plasma cell survival by transduction of signals from two known ligands, BAFF (B-cell activating factor) and APRIL (a proliferation-inducing ligand). This pathway has been shown to be important for myeloma cell growth and survival. BCMA expression is limited to B cells at later stages of development. BCMA is expressed at varying levels in myeloma patients and BCMA membrane expression is universally detected in myeloma cell lines