Early-Phase Trial of New Monoclonal Antibody Plus Pembrolizumab in Resistant Myeloma
Posted: Thursday, October 31, 2019
Enrollment began in March 2019 for a single-arm, open-label phase I/II trial to explore the clinical activity and safety of a new monoclonal antibody in combination with pembrolizumab to treat patients with relapsed or refractory multiple myeloma who have been previously treated with three or more lines of therapy. The trial, called DREAMM 4, and the novel agent, belantamab mafodotin (GSK2857916), were discussed at the European Society for Medical Oncology (ESMO) Congress 2019 in Barcelona (Abstract 1105TiP) by Suzanne Trudel, MD, MSc, of the University of Toronto, Ontario, and colleagues.
Belantamab mafodotin is a humanized (immunoglobulin G1), afucosylated, anti-BCMA monoclonal antibody that is conjugated to monomethyl auristatin F. Previously, it has shown clinical activity as monotherapy in heavily pretreated patients with multiple myeloma (overall response rate, 60%).
“PD-L1 overexpression may be a mechanism of immune evasion in multiple myeloma. Pembrolizumab…blocks the interaction of PD-1 with PD-L1 and PD-L2, [and it] may synergize with immunomodulatory drugs to enhance tumor suppression,” explained the researchers. They added that “T-cell–dependent antitumor response induced by belantamab mafodotin may be augmented by combining [it] with pembrolizumab.”
In the first, dose-escalation part of the trial, Dr. Trudel and co-investigators will evaluate two doses of belantamab mafodotin with a fixed dose of pembrolizumab in up to 12 participants, with the objectives of defining safety, tolerability, and the recommended phase II dose of the agent combined with pembrolizumab. In the second, dose-expansion part of the trial, the team will evaluate the clinical activity of the recommended phase II dose, confirm its safety, and collect pharmacokinetic information for belantamab mafodotin in up to 28 participants.
Disclosure: For full disclosures of the study authors, visit esmo.org.