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BACKGROUND: Belantamab mafodotin (belamaf) has shown promising antimyeloma activity in relapsed or refractory multiple myeloma (RRMM) as a single agent. It was hypothesized that its multimodal activity may be enhanced by programmed cell death protein 1 pathway inhibition and activation of T cell-mediated antitumor responses. This study investigated the efficacy and safety of belamaf with pembrolizumab in patients with RRMM. METHODS: DREAMM-4 (NCT03848845) was an open-label, single-arm, phase 1/2 study divided into dose-escalation (part 1) and dose-expansion (part 2) phases. Patients were ≥18 years old with ≥3 prior lines of therapy including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 agent. Patients received belamaf (2.5 or 3.4 mg/kg, part 1; 2.5 mg/kg, part 2) and 200 mg pembrolizumab for ≤35 cycles. RESULTS: Of 41 enrolled patients, 34 (n = 6 part 1, n = 28 part 2) who received 2.5 mg/kg belamaf plus pembrolizumab were included in this final analysis. Sixteen patients (47%) achieved an overall response. Minimal residual disease negativity was achieved in three of 10 patients who had very good partial response or better. Five of eight patients who had prior anti-B-cell maturation antigen therapy achieved partial response or better, including two who had B-cell maturation antigen-refractory disease. Common grade ≥3 adverse events were keratopathy (38%) and thrombocytopenia (29%). Despite belamaf-related ocular events, quality-of-life measures remained stable over time. No new safety signals were observed. CONCLUSIONS: The results of DREAMM-4 demonstrated clinical activity and a favorable safety profile of belamaf plus pembrolizumab in patients with RRMM. This trial is registered at www. CLINICALTRIALS: gov as NCT03848845.
RESUMO
BACKGROUND: Demographic diversity among clinical trials is required for representing the real-world populations intended for treatment and disease prevention. Moreover, genetic and environmental differences between ethnic and racial groups necessitate appropriately powered trials for relevant subgroups. We investigate the racial and ethnic demographic diversity of US-based participants in GSK-sponsored interventional trials. We also assess the evaluation of demographic diversity against US Census and epidemiologic data. METHODS: GSK-sponsored interventional phase I-IV clinical trials conducted from 2002 to 2019 across three areas were analyzed: pharmaceutical (includes therapeutic medicines except for vaccines and human immunodeficiency virus (HIV)), vaccine (includes prophylactic and therapeutic vaccines), and ViiV (includes HIV therapies). A total of 1005 global trials encompassing 460,707 global participants were identified, of which 495 had US-based sites with a total of 108,261 (23.5% of global) US participants (pharmaceutical, n = 357 trials; vaccine, n = 45 trials; and ViiV, n = 93 trials). We evaluated how GSK US-based trial recruitment compares with US Census (in line with previously published studies from other groups) and with epidemiologic data. RESULTS: GSK participant data for race and ethnicity combined across areas were generally similar to US Census levels (e.g. GSK versus census: White, 76.5% versus 76.3%; Black or African American, 15.1% versus 13.4%; Asian, 1.8% versus 5.9%; Hispanic or Latino, 14.0% versus 18.5%; Non-Hispanic White, 63.5% versus 60.1%). However, this was not the case for the individual pharmaceutical, vaccine, and ViiV data sets; least represented groups were Asian individuals for pharmaceutical and ViiV trials and American Indian or Alaskan Native individuals for vaccine trials (6.2%, 11.8%, and 11.1% of trials met/exceeded census level representation, respectively). The percentage of trials reaching/exceeding census levels also varied per trial phase for race and ethnicity. Furthermore, disparities in the percentage of trials reaching/exceeding census levels versus epidemiology-based prevalence levels have revealed opportunities to improve industry success metrics; in HIV trials, the proportion of Black or African American individuals (35.1%) exceeded census (13.4%) but not epidemiologic levels (55.3%). CONCLUSION: Further work is required to achieve demographic diversity across clinical trials. We conclude that US Census data are an inappropriate universal benchmark. A shift to epidemiology benchmarking will enable the consideration of global participants into US analyses for highly intrinsic (i.e. influenced by ancestry) diseases and more firm requirements for US-based participants into US analyses for extrinsic (i.e. influenced by location or culture) diseases. Benchmarking in line with epidemiologic data will allow us to set better trial enrollment goals, with the aim of conducting more demographically balanced, diverse, and representative clinical trials and enabling a better understanding of drug safety and efficacy per demographic group.