Belantamab mafodotin, an investigational antibody–drug conjugate, demonstrated a clinically meaningful overall response rate among patients with relapsed multiple myeloma in early results from the DREAMM-2 trial, according to a press release from GlaxoSmithKline. This met the primary endpoint of the pivotal phase II trial.
Hal Barron, MD
Belantamab mafodotin (GSK2857916), an investigational antibodydrug conjugate (ADC), demonstrated a clinically meaningful overall response rate (ORR) among patients with relapsed multiple myeloma in early results from the DREAMM-2 trial, according to a press release from GlaxoSmithKline (GSK). This met the primary endpoint of the pivotal phase II trial.1
Data from the DREAMM-2 study will act as the basis for regulatory filings for belantamab mafodotin that are planned for later in 2019. Further findings from the trial will be submitted for presentation at an upcoming scientific meeting.
“I am pleased with the results of the DREAMM-2 study and excited about what these data could mean for patients with multiple myeloma who have exhausted other lines of treatment. We are on track to file belantamab mafodotin later this year and continue to investigate how it could help even more patients with this disease,” said Hal Barron, MD, chief scientific officer and president of research and development at GSK, in the press release.
Belantamab mafodotin is an immuno-conjugate comprising a humanized antiB-cell maturation antigen (BCMA) monoclonal antibody that is conjugated to auristatin F through a non-cleavable linker.
DREAMM-2 is an open-label, randomized, 2-arm study that is investigating the efficacy and safety of belantamab mafodotin at 2 different doses in patients with relapsed or refractory multiple myeloma who have received 3 or more prior lines of therapy, are refractory to a proteasome inhibitor and an immunomodulatory drug, and have failed an anti-CD38 antibody (NCT03525678).
Patients were eligible to enroll onto the trial if they had an ECOG performance status of 0 to 2, adequate organ function status, and the reduction of all prior treatment-related toxicities. Prior autologous stem cell transplant was allowed if the transplant occurred more than 100 days from enrollment and if they patient had no active infections. Patients who had received an allogeneic stem cell transplant were not allowed though, nor were those who had symptomatic amyloidosis, corneal epithelial disease, active mucosal or internal bleeding, any recent major surgeries, active renal conditions, unstable liver or biliary disease, other malignancies, cardiovascular risk, active infection, HIV, hepatitis C, or presence of the hepatitis B antigen.
The participants were randomized to receive either 2.5 mg/kg or 3.4 mg/kg of intravenous frozen liquid belantamab mafodotin. An independent cohort of approximately 25 patients were also enrolled to receive a lyophilized-powder configuration of the agent. Treatment with the frozen liquid was administered in a 30 mg/vial solution that was diluted with 0.9% saline and given over 30 minutes through an infusion pump. Belantamab mafodotin treatment was given continuously once every 3 weeks until disease progression or unacceptable toxicity.
Secondary endpoints for the DREAMM-2 trial include clinical benefit rate, duration of response (DOR), time to response, progression-free survival (PFS), overall survival, time to progression, pharmacokinetics, and safety. Additionally, patients will be measured for abnormal clinical chemistry and physical parameters as well as for abnormal blood pressure, pulse rates, and body temperature. Patients will also be given quality-of-life questionnaires to complete.
In the press release, the company noted that the safety profile seen in the DREAMM-2 study was consistent with the experience from the DREAMM-1 trial.
The first-in-human, open-label phase I DREAMM-1 study explored the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and clinical activity of belantamab mafodotin in patients with relapsed/refractory multiple myeloma and BCMA-positive lymphomas. Among those with multiple myeloma, the patients had received prior alkylators, proteasome inhibitors, immunomodulatory drugs, and had undergone a stem cell transplantation.2
Part 1 of the study defined the recommended dose as 3.4 mg/kg, which was given every 3 weeks. Results from part 2 demonstrated that in 35 evaluable patients, the ORR was 60% (95% CI, 42.1%-76.1%), which included 2 stringent complete responses and 3 complete responses. The median PFS was 12 months and the median DOR was 14.3 months.
The agent was well tolerated with the most frequently reported adverse events being thrombocytopenia and corneal events.
Belantamab mafodotin is currently being investigated in 3 phase I/II trials of patients with relapsed/refractory multiple myeloma as a part of various combination regimens. Several other studies are also planned for the ADC’s development as both a single-agent and in combination regimens for patients with multiple myeloma.