Subcutaneous Isatuximab Combo Hits Primary End Points in Phase 3 Trial
The phase 3 IRAKLIA trial of subcutaneous isatuximab met its co-primary end points in multiple myeloma.
Multiple myeloma cells: © David A Litman - stock.adobe.com
Isatuximab-irfc (Sarclisa), administered subcutaneously (SC) at a fixed dose through an on-body delivery system, in combination with pomalidomide (Pomalyst) and dexamethasone was effective and well-tolerated in patients with relapsed/refractory multiple myeloma, according to data from the phase 3 IRAKLIA trial (NCT05405166).1
The trial successfully achieved its coprimary end points, showing non-inferiority in objective response rate (ORR) and observed concentration before dosing (C trough) at steady state when compared with the intravenous (IV) form of isatuximab combined with dexamethasone.
Several key secondary end points of the trial, like very good partial response, incidence rate of infusion reactions, and C trough at cycle 2, were also met with subcutaneous isatuximab.
“The consistent [ORR] and comparable efficacy and safety profile observed in the IRAKLIA study for subcutaneous [isatuximab] represent an exciting advancement, offering insight into a potential new administration option for patients,” said Sikander Ailawadhi, MD, professor of medicine in the division of hematology/oncology at Mayo Clinic Florida and lead author of the study, in a press release.1 “The results from IRAKLIA, in patients with relapsed or refractory multiple myeloma, support the potential of an on-body delivery system to help ease the delivery of a new formulation without impacting patient outcomes.”
The study is ongoing and full findings are expected to be presented at an upcoming medical conference. Regulatory submissions for subcutaneous isatuximab in the US and European Union are also planned to be sent in the first half of 2025.
About the IRAKLIA Trial
IRAKLIA, a phase 3, randomized, global, investigational, open-label trial, is assessing the efficacy and safety of SC isatuximab vs IV isatuximab when given in combination with pomalidomide and dexamethasone. Enrollment was open to patients with relapsed/refractory multiple myeloma.
Specifically, patients had to have been treated with at least 1 prior line of therapy, including lenalidomide (Revlimid) and a proteasome inhibitor.2 The study also required patients with multiple myeloma to have measurable serum M-protein of 0.5 g/dL or greater and/or urine M-protein of 200 mg/24 hours or greater and/or serum free light chain assay.
A total of 531 patients were enrolled and randomly assigned in a 1:1 ratio to receive either SC or IV isatuximab. Treatment continued until disease progression, unacceptable adverse events, patient request to discontinue therapy, or any other reason.
Those enrolled in the SC arm were given isatuximab at a fixed dose weekly for 4 weeks during cycle 1, and every 2 weeks for subsequent cycles. For those given IV isatuximab, the agent was administered at a weight-based dose via IV infusion each week for 4 weeks during cycle 1, followed by every 2 weeks for subsequent cycles.
The primary end points of the study were ORR and C trough at steady state. Very good partial response or better rate, C trough at cycle 2, incidence rate of infusion-reactions, duration of response, time to first response, time to best response, progression-free survival, and overall survival served as the secondary end points.
“We are fueled by our focus on innovation and finding best-in-class solutions to help ease the burden of disease for patients. The IRAKLIA study results are a prime example of what’s driving our scientific engine. Being able to possibly bring a novel option that helps reduce time in a healthcare facility is driven by our patient and provider-centric mindset. We look forward to sharing full results and working to bring this new advancement to the multiple myeloma community,” added Houman Ashrafian, MD, PhD, executive vice president, head of research and development at Sanofi, in the press release.1
REFERENCES
New Sarclisa subcutaneous formulation met co-primary endpoints in the IRAKLIA phase 3 study in multiple myeloma. News release. Sanofi. January 9, 2025. Accessed January 9, 2025. https://tinyurl.com/2hruuye6
SC versus IV isatuximab in combination with pomalidomide and dexamethasone in RRMM (IRAKLIA). ClinicalTrials.gov. Updated November 14, 2024. Accessed January 9, 2025. https://clinicaltrials.gov/study/NCT05405166?term=iraklia&rank=2
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