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    Treatment of Relapsed/Refractory Myeloma (excluding T-cell redirection therapy)

    (OA-58) Isatuximab Subcutaneous via an on-body Delivery System versus Isatuximab Intravenous, Plus Pomalidomide and Dexamethasone, in Relapsed/Refractory Multiple Myeloma: The Randomized Phase 3 IRAKLIA Study

    Saturday, September 20, 2025
    09:00 - 09:10 East Coast USA Time
    Location: Room 701
    Introduction: Intravenous (IV) isatuximab-pomalidomide-dexamethasone (Isa-Pd) is approved to treat relapsed/refractory multiple myeloma (RRMM) patients (pts) based on the ICARIA-MM study. A Phase 1b study showed safety and efficacy of Isa subcutaneous (SC) via an on-body delivery system (OBDS), plus Pd, in RRMM pts. Isa SC offers shorter duration, fixed dose and smaller administration volume. Here, we report results of the multicenter, open-label IRAKLIA trial (NCT05405166); Isa SC vs IV + Pd in RRMM pts, the first Phase 3 myeloma trial reporting use of an OBDS.

    Methods: Pts aged ≥18 years (y) with ≥1 prior line of therapy (LOT) were randomized 1:1 to Isa SC (1400 mg) or Isa IV (10 mg/kg) weekly in Cycle (C)1, then every 2 weeks + P (4 mg/day, Day [D]1–21) + d (40 mg [age ≥75 y: 20 mg] weekly). Pts had 4-week cycles until progression, unacceptable toxicity or patient request. Co-primary endpoints were overall response rate (ORR; non-inferiority [NI] margin, 0.839) and Isa trough level (Ctrough) at steady state (C6D1 predose; NI margin, 0.8).

    Results: 531 pts (SC n=263; IV n=268 [4 not treated]) were randomized. Baseline characteristics were balanced (median age 66 y; median 2 prior LOT). After median 12 months follow-up, ORR was 71% (SC arm) and 71% (IV arm; relative risk [95% CI] = 1.008 [0.903–1.126]; lower CI > NI margin). Mean (SD) Ctrough at C6D1 was 499 (259) μg/mL for SC and 340 (169) μg/mL for IV. Ctrough geometric mean ratio (90% CI) was 1.532 (1.316–1.784); lower CI > NI margin. Co-primary and all 4 key secondary endpoints including pt experience are in the Table. Grade ≥3 treatment-emergent adverse events occurred in 82% (SC) and 76% (IV) of pts; with treatment discontinuation rates of 8% and 9%. Injection site reactions (ISRs) occurred in 4% (11/263) of the SC arm and in 19 (0.4%) of 5145 SC injections (all Grade 1–2). 99.9% of OBDS injections were completed without interruption.

    Conclusions:

    IRAKLIA showed efficacy and pharmacokinetic NI between Isa SC vs IV. No new safety signal besides low ISR incidence was observed, showing excellent Isa SC local tolerability with OBDS. Far fewer infusion reactions and higher pt satisfaction were also noted for SC vs IV. Efficacy and safety are comparable to Isa IV in ICARIA-MM. These results support potential use of Isa SC via OBDS, designed to improve practice efficiency.

    Table


















































     

    Isa SC + Pd


    Isa IV + Pd


    Efficacy, %


    N=263


    N=268


    ORR


    71


    71


    ≥VGPR


    46


    46


    PK*, µg/mL


    N=131/121


    N=126/121


    Geometric mean Isa Ctrough at C2D1 / C6D1


    360/426


    277/278


    Safety, %


    N=263


    N=264


    All grade IR


    2


    25


    Pt satisfaction with injection method at C5D15, %


    70


    53


    *PK was analyzed at C6D1 with PP PK population and at C2D1 with PP CT4W population.
    CT4W, Ctrough at 4 weeks; IR, infusion reaction; PK, pharmacokinetics; PP, per protocol; VGPR, very good partial response.



    Funding: Sanofi. ©2025 American Society of Clinical Oncology (ASCO), Inc. Reused with permission. This abstract was accepted and previously presented at the 2025 ASCO Meeting. All rights reserved.