A Phase 1b Study of Isatuximab in Combination with Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma
Isatuximab is an anti-CD38 monoclonal antibody that kills tumor cells via multiple mechanisms. The PomdeSAR trial is a phase 1b study of isatuximab in combination with pomalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM). The preliminary findings of this study highlight the dose-escalation cohorts and the first 3 patients of the expansion cohort of the study.
For study inclusion, patients were defined as having RRMM if they had ≥2 prior MM therapies, including lenalidomide and a proteasome inhibitor. Patients were randomized to 4 isatuximab weekly doses: 5, 10, or 20 mg/kg. An expansion cohort was initiated at isatuximab 10 mg/kg (plus pomalidomide/dexamethasone) based on preliminary safety, efficacy, and pharmacokinetic data. The primary study end point was maximum tolerated dose (MTD).
A total of 26 patients were analyzed in this study. Eight, 12, and 6 patients were started on 5 mg/kg, 10 mg/kg, and 20 mg/kg of isatuximab, respectively. Patients enrolled in this trial had a median age of 65 years (range, 42-80 years) and a median of 4 (range, 3-11) prior treatment regimens, and approximately 77% of patients enrolled were refractory to prior immunomodulatory drug therapy. The overall response rate (ORR) was 75% for patients receiving isatuximab 10 mg/kg, including 2 stringent complete remissions, 8 very good partial responses, and 8 partial responses. Of note, the ORR was 60% for lenalidomide-refractory patients. The median time to first response was 4.3 weeks, and the median duration of response was 36.1 weeks. The pharmacokinetic parameters of isatuximab were not affected by the study combination.
The most common treatment-emergent adverse events, aside from infusion-associated reactions (IARs), were fatigue (65%), diarrhea (46%), and dyspnea (38%). IARs occurred in 13 (50%) patients (grade ≥3 in 1 patient), but only with the first infusion in most patients. MTD was not reached at this point in the analysis.
The preliminary findings of this study showed that the combination of isatuximab with pomalidomide and dexamethasone was tolerable and clinically active in heavily pretreated patients with RRMM. This combination is currently being studied in a phase 3 trial.
Mikhael J, et al. ASCO Abstract 8007.