Citations

Abstract Introduction: IRAKLIA (NCT05405166) is an ongoing, global, non-inferiority trial of isatuximab (Isa) subcutaneous (SC) administration plus pomalidomide-dexamethasone (Pd), and the first Phase 3 multiple myeloma (MM) trial using an on-body injector (OBI) for SC administration. In IRAKLIA, Isa SC OBI demonstrated non-inferiority in the 2 co-primary endpoints of efficacy and pharmacokinetics compared with Isa intravenous (IV). Significantly more patients expressed higher satisfaction with Isa SC OBI vs Isa IV in IRAKLIA, and more patients and health care providers (HCPs) preferred Isa SC OBI over Isa SC manual push in the Phase 2 IZALCO trial (NCT05704049). The Isa OBI is a wearable, automated injector that adheres to the skin of the abdomen and administers Isa SC with the push of a button without any batteries or electronics. The Isa SC OBI offers hands-free administration; a small, hidden, retractable needle to prevent sharps injury and reduce patient anxiety; low-pressure delivery; a simplified user interface; and flexible administration in either outpatient or home settings. Here, we examine the safety of Isa SC OBI administered by trained nursing professionals during at-home patient visits in IRAKLIA. Methods In IRAKLIA, patients with relapsed/refractory MM (RRMM) aged ≥18 years with ≥1 prior line of therapy (LOT) were randomized 1:1 to Isa SC OBI (1400 mg; n=263) or IV (10 mg/kg; n=264) weekly in Cycle (C)1, then every 2 weeks + P (4 mg/day, Day [D]1–21) + d (40 mg [20 mg if age ≥75 years] weekly) in 4-week cycles. Home administration by a HCP was proposed as an option after 5 cycles for Isa OBI arm patients on D15 from C6 onward, and D1 visits from C6 remained clinic based. Eligibility for home-administration depended on an absence of infusion reactions (IRs) at C4 and C5, hematology test results at D1 of each cycle, investigator judgement, and patient willingness. During at-home visits, providers prepared and applied Isa SC OBI and safely disposed of the device upon completion. Following at-home administration, providers evaluated the injection site for reactions, took vitals, and completed documentation. No specific monitoring was planned after the end of injections. At-home administration was not allowed in some countries due to local regulations. Results In the ongoing IRAKLIA trial, 202 patients were treated with Isa SC OBI within countries where at-home administration was permissible. 11 (5.4%) of these patients from 5 different countries [Australia (n=6), Hungary (n=2), Italy (n=1), Norway (n=1), and Spain (n=1)] have participated in home administration as of the cutoff date (06-Nov-2024), with additional sites and countries initiated after the cutoff date. First at home administrations started at Cycle 6 for the majority of patients (n =7) and at Cycle 7 (n =1), Cycle 8 (n =2), and Cycle 10 (n =1) for the remaining patients. Among the 11 patients participating in at-home visits, more than half switched to at-home administration and have not returned to the hospital for their next Day 15 cycle visit. 55 injections were performed at home. The median injection duration was the same between clinic and at-home administration (13 minutes). Similar to Isa SC OBI use in the clinic, home administration was well tolerated with no new safety signals and a 100% completed injection rate. No at-home Isa OBI administration was omitted or interrupted during the injection. At-home administration had a very low rate of injection-site reactions (ISR; n=1). The single ISR was a Grade 1 episode consisting of injection swelling, which resolved within the same day, and most subsequent Day 15 administrations were performed at home for this patient. No other adverse events (AEs), including no IRs, were linked to at-home visits. No device event linked to at-home visits was reported. Conclusions Initial data from the ongoing IRAKLIA trial support the safety of at-home administration of Isa SC OBI for the treatment of patients with MM. Home administration was well tolerated, with no safety concerns and a median injection time of 13 minutes consistent with in-clinic use of Isa SC OBI. The option of either home or outpatient administration of Isa SC OBI for patients with MM allows for greater flexibility and accessibility of treatment, with the potential to improve patient care and reduce common barriers to patient retention and therapy compliance.

Abstract Background: Intravenous (IV) isatuximab plus pomalidomide and dexamethasone (Isa-Pd) is approved for treatment in patients with relapsed/refractory multiple myeloma (RRMM) based on the ICARIA-MM study. Subcutaneous (SC) administration of Isa offers potential advantages such as shorter administration duration and greater patient comfort compared with IV routes. Isa SC via an on-body injector (OBI), an investigational wearable bolus injector, demonstrated safety and efficacy in a Phase 1b study in patients with RRMM. The IRAKLIA trial (NCT05405166) was the first Phase 3 trial evaluating the non-inferiority of Isa-Pd SC via an OBI vs Isa-Pd IV in patients with RRMM. Here, we report the findings of the IRAKLIA trial in the East Asian subgroup with RRMM. Methods: This global, multicenter, open-label study enrolledpatients aged ≥18 years with RRMM who had received ≥1 prior line of therapy (LOT) including lenalidomide and a proteasome inhibitor (PI). Patients were randomized 1:1 to Isa SC (1400 mg) or Isa IV (10 mg/kg) weekly in Cycle (C)1, then every 2 weeks in addition to P (4 mg orally daily, Day [D]1-21) and d (40 mg orally [20 mg if age ≥75 years] weekly). Treatment was administered in 4-week cycles and continued until disease progression, unacceptable toxicity, or patient withdrawal. Co-primary endpoints included overall response rate (ORR) and observed Isa concentration before dosing (Ctrough) at steady state (predose at C6D1). Key secondary endpoints included rate of very good partial response or better (≥VGPR), Ctroughlevel Cycle 2 Day 1 (C2D1), infusion reaction incidence, and patient satisfaction rate based on the patient experience and satisfaction questionnaire (PESQ) at C5D15. Results: The East Asian subgroup consisted of 105 patients from China (Mainland, n=82 and Taiwan, n=1) and Japan(n=22) (SC, n=50; IV, n=55). Baseline characteristics of the East Asian subgroup were generally balanced between the two arms and generally comparable to the overall global population (median age 62 years; median 2 prior LOT; 29.5% high-risk cytogenetics; 82.9% refractory to lenalidomide; 7.6% prior exposure to daratumumab). After a median of 13.0 months follow-up, ORR in the SC and IV arm was 74.0% and 70.9%, respectively (relative risk [95% CI] = 1.044 [0.815 – 1.335]). The mean (SD) of Ctroughat C6D1 was 502 (232) µg/mL for SC arm and 282 (123) µg/mL for IV arm. The geometric mean ratio (90% CI) comparing SC to IV for Ctrough at steady state was 1.756 (1.346 – 2.290). The ≥VGPR rates were 58.0% for SC and 50.9% for IV (relative risk [95% CI] = 1.139 [0.798 – 1.631]). The mean(SD) of C2D1 Ctroughlevel was 420 (161) µg/mL for the SC arm and 262 (111) µg/mL for IV arm. The geometric mean ratio (90% CI) comparing SC to IV for Ctrough at C2D1 was 1.673 (1.321 to 2.120). The infusion reaction incidence was 0% and 21.8% for SC and IV, respectively. Grade ≥3treatment-emergent adverse events were observed in 82.0% and 87.3% of patients in the SC and IV arms, respectively. Treatment discontinuation rates were 6% for the SC arm and 12.7% for the IV arm. Injection site reactions (ISRs) occurred in 4% (2/50) of patients in the SC arm and in 0.21% (2/964) of SC injections (all Grade 1), with 99.3% of SC injections completed successfully. Isa SC patients expressed higher satisfaction with their injection method, with 64.0% of patients reporting “satisfied” or “very satisfied” vs 52.7% of Isa IV patients (odds ratio [95% CI] = 1.594 [0.728 – 3.489]). Conclusions: The efficacy, safety and pharmacokinetic results between Isa SC vs IV + Pd in the East Asian population from the IRAKLIA study were consistent with the results of the overall global population, in which non-inferiority of ORR, Ctrough at C6D1, ≥VGPR and Ctrough at C2D1 was demonstrated and statistically significantly fewer infusion reactions and higher patient satisfaction were also noted for SC vs IV. These results support the potential use of Isa SC delivered via OBI in East Asian patients and demonstrate the potential of this delivery method to improve patient experience and practice efficiency.