Updated data from a phase II dose finding trial of single agent isatuximab (SAR650984, anti-CD38 mAb) in relapsed/refractory multiple myeloma (RRMM).

8005 Background: Isatuximab (ISA) is a humanized anti-CD38 monoclonal antibody with multiple modes of action for killing tumor cells through direct tumor targeting and immune cell engagement. Here, we report updated data from an ongoing Phase II dose finding study of ISA monotherapy in patients (pts) with RRMM (NCT01084252). Methods: Pts with RRMM (≥3 lines of anti-MM therapy or refractory to immunomodulatory drugs [IMiDs] and proteasome inhibitors [PIs]) were randomized to ISA 3 mg/kg Q2W, 10 mg/kg Q2W x 2 cycles then Q4W, or 10 mg/kg Q2W. Randomization stratified by prior pomalidomide and/or carfilzomib therapy. Emerging PK data prompted enrollment of a 4th treatment arm at 20 mg/kg QW x 4 doses then Q2W. 1 cycle = 28 days. Primary objective: evaluation of ISA activity (overall response rate [ORR; IMWG]). Results: 97 pts treated: median age, 62.5 (38–85) y; median time from diagnosis, 5.9 (1.2–24.1) y; ISS stage 3, 37%; median prior lines of therapy, 5 (2–14); 86%, 61%, 80%, 57%, 88% refractory to lenalidomide, pomalidomide, bortezomib, carfilzomib, or IMiD+PI, respectively. 24/56 cytogenetics-evaluable pts (43%) had t(4;14) and/or del(17p). Median treatment duration, 13.1 wks; 22 pts remain on treatment (cut-off Nov 2015). ORR: 9% (2/23), 20% (5/25), 29% (7/24) & 24% (6/25) at ISA 3 Q2W, 10 Q2W/Q4W, 10 Q2W, & 20 mg/kg QW/Q2W, respectively; 14/20 responders continue without progression. At ≥10 mg/kg: ORR was 24% (18/74), similar in subgroups (age, CrCl, prior lines of therapy), and 44% (8/18) in pts with abnormal cytogenetics. Median time to 1st response, 1.35 mo; median duration of response at data cut-off, 6.6 mo. Most common adverse events (AEs) were nausea (33%), fatigue (30%), dyspnea (26%), and cough (24%), which were typically grade ≤2. Infusion-associated reactions (IARs) occurred in 49% of pts, mostly grade ≤2, 94% during the 1st infusion. 6 pts discontinued therapy due to AEs, 2 due to IARs. Conclusions: ISA monotherapy is active and generally well tolerated in heavily pretreated RRMM, with efficacy greatest at ≥10 mg/kg (ORR 24%). ORR was similar in subgroups, including high-risk cytogenetics. Progression-free survival and overall survival data will be presented. Clinical trial information: NCT01084252.