MM-096: Isatuximab Short-Duration Fixed-Volume Infusion Combination Therapy for Relapsed/Refractory Multiple Myeloma: Final Results of a Phase 1b Feasibility/Safety Study

Context: To reduce infusion duration, fixed-volume infusion of isatuximab (Isa), a CD38 monoclonal antibody, was confirmed to be feasible and safe in the primary analysis. Objective: Evaluate efficacy and safety of a fixed-volume infusion of Isa plus pomalidomide and dexamethasone (Pd) in relapsed/refractory multiple myeloma (RRMM). Design: This two-part, Phase 1b study ( NCT02283775 ) enrolled RRMM patients who had received ≥2 prior lines of therapy, including lenalidomide and a proteasome inhibitor, and who demonstrated disease progression. Part A was an Isa dose-escalation study. In Part B, Isa (10 mg/kg) was administered as a fixed infusion volume of 250 mL (mL/h infusion rate) with standard doses of Pd. The primary endpoint for Part B was incidence of Grade (Gr) ≥3 infusion reactions (IRs) during the first 6 Isa infusions. Secondary endpoints included duration of infusion, safety, efficacy, and immunogenicity. Results: Of 47 patients enrolled in Part B, 22 (47%) remained on treatment at data cut-off. Patients were heavily pretreated, with a median of 3 prior treatment lines (range, 1–8). Median duration of exposure was 36.9 weeks (range, 1–77). IRs were reported in 19/47 (40%) patients, all Gr 2, and occurred only during first infusion. Median duration of the first, second and ≥3 infusions was 3.7, 1.8, and 1.2 hours, respectively. All patients experienced ≥1 treatment-emergent adverse event (TEAE). The most common non-hematologic TEAEs were fatigue (64%), IRs, cough, and upper respiratory tract infection (40% each); 6 patients (13%) died within 30 days of final study treatment. The overall response rate was 53% in all patients. Median time to first response was 0.95 months (range, 0.9–3.4). At a median duration of 9.9 months follow-up (range, 0–17.3), median duration of response, progression-free survival, and overall survival were not reached. Conclusions: Efficacy and safety findings were consistent with Part A of this study and the pivotal Phase 3 ICARIA study. Measurements of response were robust. There were no Gr ≥3 IRs, and all occurred during first infusion. These results confirm the safety, efficacy, and feasibility of Isa administered by a fixed infusion volume. Funding for this study was provided by Sanofi.