SAR446523
SAR446523 Receives FDA Orphan Drug Designation for R/R Myeloma
The FDA has granted Orphan Drug Designation to the GPRC5D-targeted monoclonal antibody SAR446523 as a potential therapeutic option for patients with relapsed or refractory multiple myeloma. SAR446523 is a GPRC5D monoclonal antibody developed by Sanofi. The phase 1 trial includes dose-escalation and optimization phases, enrolling patients with specific prior treatment histories.
SAR446523 is an investigational IgG1-based monoclonal antibody that also features an engineered fragment crystallizable domain intended to enhance antibody-dependent cell-mediated cytotoxicity. The agent is currently being evaluated in a first-in-human phase 1 trial (NCT06630806) in this patient population.
“The orphan drug designation is a significant milestone in our ongoing efforts to develop innovative treatments in multiple myeloma,” Alyssa Johnsen, MD, PhD, global therapeutic area head of Immunology and Oncology Development at Sanofi, stated in a news release. “This underscores our commitment to multiple myeloma, a disease for which we have acquired strong expertise with the development of another widely used and approved immunotherapy treatment.”
The first-in-human study includes both dose-escalation and -optimization portions, and investigators are enrolling patients at least 18 years of age with a documented diagnosis of multiple myeloma who have measurable disease. All patients must have an ECOG performance status of 0 or 1 and adequate organ and bone marrow function.
In the dose-escalation portion, at least 3 prior lines of therapy are required for enrollment; patients must have disease that is either relapsed or refractory to those prior therapies, or they need to be intolerant to them. During dose optimization, at least 3 prior lines of therapy are required, and patients need to be relapsed or refractory to an immunomodulatory drug, proteasome inhibitor, anti-CD38 monoclonal antibody, and anti-BCMA targeting therapy.
Up to 6 dose levels of SAR446523 are being evaluated during dose escalation with the goal of determining the maximum administered dose, maximum tolerated dose, and recommended dose range for regimens that will be tested in dose optimization.
During dose optimization, patients will be randomly assigned 1:1 to receive SAR446523 at one of the selected doses established in part 1 of the study, with the goal of determining the recommended phase 2 dose.
The incidence of dose-limiting toxicities is the primary end point in dose escalation. Overall response rate (ORR) is serving as the primary end point for dose optimization. Secondary end points include safety (both parts), ORR (dose escalation only), very good partial response or better rate, clinical benefit rate, time to response, progression-free survival, and minimal residual disease status.
The study was initiated in October 2024 and is currently enrolling patients at 9 locations in the United States, Canada, Australia, and Italy. Investigators will enroll an estimated 82 patients, and the estimated primary completion date of the study is November 2028.
