GSK's ADC Combination Therapy Shows 78% Overall Response Rate in Relapsed/Refractory Multiple Myeloma

Today, GSK announced that its antibody-drug conjugate (ADC) belantamab mafodotin, which targets B-cell maturation antigen (BCMA), has further demonstrated its potential in treating patients with relapsed/refractory multiple myeloma (R/R MM) in the DREAMM-2 and DREAMM-6 clinical trials. Currently, the Biologics License Application (BLA) for this therapy is under review by the U.S. FDA.

Multiple myeloma is caused by the malignant transformation of plasma cells in the bone marrow. The abnormal proliferation of plasma cells impairs the production of normal blood cells, leading to damage to the bones, immune system, and kidneys. Although various therapies can effectively treat multiple myeloma, tumor cells typically develop resistance to existing treatments and relapse occurs. Therefore, the development of innovative therapies is crucial.

Belantamab mafodotin is one of GSK’s key research and development programs. It conjugates a humanized anti-BCMA antibody with a cytotoxic agent, specifically delivering the cytotoxic payload into multiple myeloma (MM) cells by targeting BCMA, thereby exerting anticancer effects. BCMA has emerged as a highly prominent therapeutic target in recent years. It is a transmembrane glycoprotein belonging to the tumor necrosis factor (TNF) receptor superfamily, also known as TNFRSF17 or CD269. A notable feature of this protein is its high expression on all MM cells, while it is not expressed in other normal tissues except plasma cells. Consequently, BCMA has become a popular target for numerous pharmaceutical companies and research institutions developing therapies for patients with relapsed/refractory multiple myeloma (R/R MM). Previously, belantamab mafodotin received Breakthrough Therapy Designation and Priority Review from the U.S. Food and Drug Administration (FDA).

▲Belantamab mafodotin is a key R&D project in which GSK has high hopes (Image source: Reference [2])

Patients with relapsed/refractory multiple myeloma (R/R MM) who had previously received immunomodulatory agents, proteasome inhibitors, and anti-CD38 antibodies were enrolled in the DREAMM-2 study. Thirteen-month follow-up data from this study showed that the median duration of response (DoR) was 11 months and the median overall survival (OS) was 14.9 months among patients treated with belantamab mafodotin monotherapy at a dose of 2.5 mg/kg. The overall response rate (ORR) was 32%, consistent with the data at 6 months of treatment. Among patients who achieved a response, the majority (58%) attained a very good partial response, including 2 stringent complete responses and 5 complete responses.

The DREAMM-6 study evaluated the efficacy of belantamab mafodotin in combination with bortezomib/dexamethasone (BorDex) for treating patients whose disease remained refractory or relapsed after first-line therapy. In the early analysis of this trial, the combination therapy achieved an overall response rate (ORR) of 78%, with 50% of patients attaining a very good partial response and 28% achieving a partial response.

“The latest results from the DREAMM-2 study further demonstrate the therapeutic potential of belantamab mafodotin, helping to address significant unmet needs in patients with multiple myeloma,” said Dr. Axel Hoos, Senior Vice President and Head of Oncology R&D at GSK. “We are encouraged by these preliminary results from the DREAMM-6 study, which highlight the therapeutic potential of belantamab mafodotin combination therapy in patients with earlier-stage multiple myeloma, and we look forward to obtaining and sharing the full data from this trial.”

References:

[1] DREAMM-2 and DREAMM-6 data at ASCO reinforce the potential of GSK's investigational belantamab mafodotin in patients with relapsed/refractory multiple myeloma. Retrieved 2020-05-27, from https://www.prnewswire.com/news-releases/dreamm-2-and-dreamm-6-data-at-asco-reinforce-the-potential-of-gsks-investigational-belantamab-mafodotin-in-patients-with-relapsedrefractory-multiple-myeloma-301066006.html

[2] GSK Q2 2019 Results. Retrieved 2020-05-27, from https://www.gsk.com/media/5668/q2-2019-results-slides.pdf

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