Encouraging results for low-dose belantamab mafodotin plus nirogacestat in patients with RRMM

Low-dose belantamab mafodotin plus nirogacestat showed encouraging efficacy results in patients with relapsed/refractory multiple myeloma (RRMM) in the phase 1/2 DREAMM 5 platform study. Further exploration of this combination therapy is warranted.

Belantamab mafodotin, a B-cell maturation antigen (BCMA)-targeting antibody-drug conjugate, was approved in Europe for the treatment of patients with MM who had received 4 or more prior lines of therapy and were refractory to a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody. Nirogacestat is an investigational gamma-secretase inhibitor that has displayed encouraging preclinical results in MM.

The phase 1/2 DREAMM 5 platform study (NCT04126200) assessed whether the combination of low-dose belantamab mafodotin plus nirogacestat resulted in a similar efficacy but an improved ocular safety profile compared with belantamab mafodotin monotherapy [1]. 81 participants were analysed: 10 from the dose-exploration cohort, 34 from the cohort expansion phase receiving combination therapy, and 37 from the monotherapy arm. The primary endpoint was the overall response rate (ORR). Prof. Sebastian Grosicki (Medical University of Silesia, Poland) presented the findings.

The reported ORRs were 29% in the combination therapy group and 38% in the monotherapy group. Incorporating posterior probability distribution resulted in median ORR values of 36% and 33%, respectively. The safety profile of the combination therapy was consistent with the known safety profiles per monotherapy agent. Although the rates of ocular events were similar between participants in the combination therapy (71%) and the monotherapy group (78%), high-grade events were more common in the monotherapy group than in the cohort expansion group (grade 1: 21% vs 5%; grade 2: 21% vs 14%; grade 3: 29% vs 59%; combination vs mono-therapy, respectively).

In conclusion, these data support further exploration of low-dose combination therapy belantamab mafodotin plus nirogacestat in patients with RRMM

1. Grosicki S, et al. Low-dose belantamab mafodotin (belamaf) in combination with nirogacestat vs belamaf monotherapy in patients with relapsed/refractory multiple myeloma (RRMM): Phase 1/2 DREAMM-5 platform sub-study 3. P913, EHA 2023 Annual Congress, 8─11 June, Frankfurt, Germany.

 

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Posted on 2 August 202318 March 2024