Dr. Carlo-Stella on the Investigation of RG6234 in R/R Multiple Myeloma

Carmelo Carlo-Stella, MD, PhD, Department of Biomedical Sciences, Humanitas University, Department of Oncology and Hematology, IRCCS Humanitas Research Hospital in Rozzano, Italy, discusses the evaluation of subcutaneous and intravenous (IV) RG6234 in relapsed/refractory multiple myeloma.

A phase 1 dose-escalation trial (NCT04557150) evaluated both subcutaneous and IV RG6234 in patients with heavily pretreated multiple myeloma who previously received treatment with an immunomodulatory drug and proteasome inhibitor and are intolerant to or have no other option for standard-of-care treatment.

Updated results presented at the 2022 ASH Annual Meeting showed that patients who received IV RG6234 experienced an overall response rate (ORR) of 71.4%, and those in the subcutaneous RG6234 cohort had an ORR of 63.6%. Notably, 50% of patients in the IV cohort achieved a very good partial response or better. Additionally, 71.4% of patients who achieved complete remission (CR) became minimal residual disease negative.

RG6234 is a GPRC5DxCD3 T-cell engaging bispecific antibody that targets CD3 cells and multiple myeloma plasma cells, Carlo-Stella explains. Upon the antibody aligning with the bindings of the T-cells and myeloma cells, the T-cells are activated, in turn producing cytokines that target myeloma plasma cells, Carlo-Stella says.

Due to their off-the-shelf nature and ease of use, bispecific antibodies have gained more traction across hematologic malignancies in recent years, Carlo-Stella notes, adding that this shift has largely occurred across the landscape of lymphoproliferative disorders. These agents have created high expectations for both physicians and patients, Carlo-Stella emphasizes.

At this stage in development, RG6234 remains under evaluation in a phase 1 clinical trial that has enrolled 108 patients with relapsed/refractory multiple myeloma. Approximately half of these patients have been treated with IV RG6234, and the other half were treated subcutaneously, Carlo-Stella notes. Investigators hope to develop RG6234 as a subcutaneous drug as a fixed-duration therapy, Carlo-Stella concludes.