KEY TAKEAWAYS
- The phase 1 DREAMM-20 trial aimed to assess the safety, tolerability, and recommended dose of belantamab, an anti-BCMA monoclonal antibody.
- The study involves administering intravenous belantamab to patients on days 1 and 15 of a 28-day cycle.
- The study includes patients with relapsed or refractory MM who have previously received at least three prior courses of treatment, including specific agents such as immunomodulatory agents, proteasome inhibitors, and anti-CD38 antibodies.
- The study provided crucial information on the safety, tolerability, and recommended dose of belantamab, a promising anti-BCMA.
Multiple myeloma (MM) is an intractable malignant clonal plasma cell disorder that accounts for 10% of all hematologic malignancies worldwide. Combinations of proteasomeinhibitors (PIs), immunomodulatory medications, monoclonal antibodies, alkylating agents, and corticosteroids are used to treat multiple myeloma (MM), in addition to the more recent chimeric antigen receptor (CAR) T-cell therapies, antibody-drug conjugates (ADCs), and bispecificantibodies. Given the toxicity of current standards of care, emerging treatments, and the frequency of relapse, there is a substantial unmet need for new efficacious therapies with improved safety profiles. BCMA, a cell surface receptor expressed on B-lymphocytes and plasma cells, is upregulated in MM cells. BCMA has been clinically validated as a treatment target for multiple myeloma. Belantamab (GSK2857914) is an anti-BCMA humanizedafucosylated IgG1 monoclonal antibody. The monoclonal antibody structure of belantamab is identical to that of the ADC belantamab mafodotin, minus the monomethyl auristatin-F payload.
According to preclinical data, the mechanism of action of belantamab is antibody-dependent cellular cytotoxicity through increased FcRIII binding, antibody-dependent cellular phagocytosis, and blocking of BCMA-mediated pro-survival and proliferative signaling. In vitro, belantamab is active against multiple myeloma (MM) cell lines, primary patient samples, and mouse xenografts; evidence from preclinical studies supports clinical investigation for MM.
Part 1 of DREAMM-20 is a phase 1, multicenter, open-label, dose-escalation study of patients with relapsed or refractory multiple myeloma (MM) to determine the safety, tolerability, and recommended dose for Part 2 of belantamab. Inclusion criteria include patients 18 years old with confirmed MM (as defined by the International Myeloma Working Group [IMWG]), measurable disease, an Eastern Cooperative Oncology Group performance status of 0-2, and adequate organ system function. Patients must have received at least three prior courses of treatment, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody (unless contraindicated or unavailable). The receipt of BCMA-targeted agents in advance is permitted. Essential exclusion criteria include current corneal epithelial disease except for nonconfluent superficial punctate keratitis, signs of meningeal or CNS involvement with MM, and evidence of cardiovascular risks.
To participate, patients must provide informed consent. Patients will receive intravenous belantamab on days 1 and 15 of every 28-day cycle. Using the modified toxicity probability interval procedure, the dose will be increased. The primary endpoint is the incidence of adverse events, including dose-limiting toxicities, as measured by National Cancer Institute-Common Toxicity Criteria for Adverse Events v5.0.Secondary endpoints include pharmacokinetics, incidence of anti-drug antibodies, and overall response rate (evaluated according to IMWG criteria from 2016). Among the exploratory endpoints are pharmacodynamics and quality of life, longitudinal soluble BCMA and M-protein levels, and additional biomarker evaluations. On peripheral blood and bone marrow, biomarker and pharmacokinetic assessments will be conducted. Part 1 data will inform subsequent study parts’ dose(s), schedule, and prospective combination partners.
Source: https://library.ehaweb.org/eha/2023/eha2023-congress/386812/hang.quach.dreamm-20.a.study.to.investigate.the.safety.and.efficacy.of.html?f=menu%3D16%2Abrowseby%3D8%2Asortby%3D2%2Ace_id%3D2489%2Aot_id%3D27922%2Atrend%3D4016%2Amarker%3D4178
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT05714839
Hang Quach, Giulia Fulci, Nirav Ratia, John Clements, Eric Lewis, Malika Ahras, Sarantos Kaptanis, Brandon E. Kremer/DREAMM-20: A STUDY TO INVESTIGATE THE SAFETY AND EFFICACY OF BELANTAMAB FOR THE TREATMENT OF MULTIPLE MYELOMA WHEN USED AS MONOTHERAPY AND IN COMBINATION TREATMENTS/Inc, M. G. (n.d.). DREAMM-20: A STUDY TO INVESTIGATE THE SAFETY AND EFFICACY OF… by Hang Quach. Library.ehaweb.org. Retrieved July 14, 2023, from https://library.ehaweb.org/eha/2023/eha2023-congress/386812/hang.quach.dreamm-20.a.study.to.investigate.the.safety.and.efficacy.of.html?f=menu%3D16%2Abrowseby%3D8%2Asortby%3D2%2Ace_id%3D2489%2Aot_id%3D27922%2Atrend%3D4016%2Amarker%3D4178
