SAN FRANCISCO—Patients with relapsed or refractory multiple myeloma treated with the anti-CD-38 monoclonal antibody, SAR650984, in combination with lenalidomide/dexamethasone had an overall response rate (ORR) of 58% and a clinical benefit rate (CBR) of 65% (Abstract 83), results of a phase 1b trial reported at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition.
“Responses were seen following the first cycle of therapy and deepened with continued treatment,” said Thomas G. Martin III, MD, of the Department of Medicine at the University of California, San Francisco in San Francisco, CA.
The trial treated patients with SAR650984 in a standard dose escalation fashion in three cohorts of 3, 5, and 10 mg/kg every 2 weeks with lenalidomide and dexamethasone on a 28-day cycle. SAR650984 was administered intravenously on day 1 and 15.
A total of 31 patients were treated, 18 in the expansion cohort. The median number of prior treatment regimens was 7 (range, 2-14); 74% of patients were relapsed and refractory to their last lenalidomide-containing regimen; 29%, to their last pomalidomide-containing regimen; 55%, to their last bortezomib-containing regimen; and 48%, to their last carfilzomib-containing regimen.
Median PFS differed by prior lines of therapy. Overall, median PFS was 6.2 months (95% confidence interval [CI] 4.80-13.33); among the 24 patients who had received 3 or more lines of therapy, median PFS was 5.8 months (95% CI 2.10-10.30) and among the 7 patients who had received 1 to 2 lines of therapy, median PFS was not reached (95% CI 6.2-NR).
The ORR was 63% at the SAR650984 10 mg/kg dose level, 8% stringent complete response (CR), 29% very good partial response, 25% partial response, and 4% minimal response, for a CBR of 67%. In the 25 patients were relapsed/refractory to lenalidomide, the ORR was 48% and, among the 6 patients who had not relapsed to but were refractory to lenalidomide, the ORR was 100%.
Of the 31 patients, 6 had stable disease, 4 had progressive disease, and 1 was not evaluable. Two patients discontinued treatment due to infusion reactions, 1 for a serious grade 3 anaphylactic reaction in cycle 1 in the 3 mg/kg cohort, and 1 for a nonserious grade 3 maculopapular rash in cycle 2 at the 10 mg/kg cohort. These adverse events resolved in both patients.
The most common treatment-emergent hematologic adverse events were anemia, neutropenia, and thrombocytopenia; nonhematologic events were fatigue, diarrhea, and nausea. No dose-limiting toxicities were reported. Pharmacokinetic analysis revealed no drug-drug interaction between SAR650984 and lenalidomide.
The maximum tolerated dose was not reached.