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belantamab mafodotin + nirogacestat + pomalidomide
- Development stage
- Phase 1
- Lead developer
- GSK
- Modality
- Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics, Small Molecules
- Administration
- Intravenous, Oral
01
Overview
This combination therapy consists of the antibody-drug conjugate (ADC) belantamab mafodotin, the gamma-secretase inhibitor nirogacestat, and the immunomodulatory agent pomalidomide. It is currently being investigated in a Phase 1 dose-escalation study led by Memorial Sloan Kettering Cancer Center for the treatment of relapsed or refractory multiple myeloma. Belantamab mafodotin targets B-cell maturation antigen (BCMA) on the surface of myeloma cells to deliver the cytotoxic microtubule inhibitor monomethyl auristatin F (MMAF). Nirogacestat is included in the regimen to inhibit gamma-secretase, an enzyme responsible for the cleavage and shedding of BCMA from the cell surface; by preventing this shedding, nirogacestat potentially increases BCMA density and enhances the binding and efficacy of the ADC. Pomalidomide further augments the anti-tumor response through its immunomodulatory effects. While belantamab mafodotin previously received accelerated FDA approval as a monotherapy, that approval was withdrawn in 2023 following the results of the DREAMM-3 trial.
- Other names
- belantamab mafodotin-blmf
02
Targets
BCMA (B-cell maturation antigen)CRBN (Cereblon)GSEC (Gamma-Secretase Complex)
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