Subcutaneous Isatuximab Shows Noninferior ORR, C Trough in R/R Myeloma

Subcutaneous isatuximab yields noninferior results vs intravenous isatuximab when paired with pomalidomide and dexamethasone in the phase 3 IRAKLIA trial.

Fixed-dose, subcutaneous isatuximab-irfc (Sarclisa) delivered via an on-body delivery system in combination with pomalidomide (Pomalyst) and dexamethasone met the phase 3 IRAKLIA trial’s (NCT05405166) coprimary end points of non-inferior objective response rate (ORR) and observed concentration before dosing (C trough) at steady state compared with intravenous isatuximab plus dexamethasone in patients with relapsed/refractory multiple myeloma, according to a press release from the developer, Sanofi.¹

In the US and European Union, regulatory submissions for subcutaneous isatuximab are planned to be sent in the first half of 2025.

IRAKLIA is a global, investigational, open-label, randomized phase 3 trial evaluating the efficacy and safety of subcutaneous isatuximab vs intravenous isatuximab when combined with pomalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma who have received at least 1 previous line of therapy that included lenalidomide (Revlimid) and a proteasome inhibitor.²

“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,” Sikander Ailawadhi, MD, professor of medicine in the division of hematology/oncology at Mayo Clinic Florida and lead author of the study, said in the 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.”

Data collection and drug administration remain ongoing; the full study results will be presented at an upcoming medical conference.

In addition to meeting both co-primary end points, several key secondary end points including very good partial response, incidence rate of infusion reactions, and C trough at cycle 2 were met with subcutaneous isatuximab.

The trial’s primary end points were ORR and C trough at steady state.² Secondary end points include 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.

The IRAKLIA trial enrolled a total of 531 patients who were randomly assigned, in a 1:1 ratio, to receive either subcutaneous or intravenous isatuximab. Administration continued until disease progression, unacceptable adverse events, or patient request to discontinue therapy for any reason.

Regarding dosage, subcutaneous isatuximab was delivered at a fixed-dose via the Enable Injections’ enFuse® hands-free on-body delivery system once a week for 4 weeks during the first 28-day cycle, then every 2 weeks for the following cycles. Intravenous isatuximab was delivered at a weight-based dose via infusion once a week for 4 weeks during the first cycle, then every 2 weeks for following cycles. Oral pomalidomide was administered from day 1 to day 21 of each cycle, and oral dexamethasone was administered on days 1, 8, 15, and 22 of every cycle.

Eligible patients were those with multiple myeloma who received at least 1 prior line of anti-myeloma therapy that included lenalidomide and a proteasome inhibitor either alone or in combination and had 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.

Patients were excluded for the following reasons: if they had primary refractory multiple myeloma, had prior anti-CD38 treatment less than 9 months before randomization or were intolerant to the anti-CD38 agent previously received, had prior therapy with pomalidomide, had inadequate biological tests, had significant cardiac dysfunction, had concomitant plasma cell leukemia, or had known acquired immunodeficiency syndrome or human immunodeficiency virus requiring antiviral treatment.

References

1. 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
2. SC versus IV isatuximab in combination with pomalidomide and dexamethasone in RRMM (IRAKLIA). ClinicalTrials.gov. Updated November 14, 2024. Accessed January 9, 2025. https://tinyurl.com/mpyvr2hp