This is a multicenter, open-label phase II study in subjects with relapsed and/or refractory multiple myeloma with at least two prior lines of therapy.
This trial is currently open and accepting patients.
The study is divided into two parts:
Part 1 (Run-in safety phase): In this safety-run in phase a total of six subjects will be enrolled at the coordinating site (Medical College of Wisconsin) to assess potential dose-limiting toxicities that may be associated with the addition of isatuximab with pomalidomide, elotuzumab and dexamethasone.
Part 2 (Expansion phase): In this part, up to 47 additional subjects will be enrolled.
The study hypothesis is that the isatuximab in combination with elotuzumab, pomalidomide, and dexamethasone (Isa-EPD) will be safe and lead to superior response rates than seen with either isatuximab with pomalidomide and dexamethasone or elotuzumab with pomalidomide and dexamethasone in subjects with relapsed and/or refractory multiple myeloma.
The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.
Inclusion Criteria:
Exclusion Criteria:
Phase 2
Enrollment: 53 patients (estimated)
View MoreDecember 10, 2023
Results: At the time of data cut-off, 15 patients were enrolled. Median age was 68 years (range, 54-79) and 3 were African American. Disease was refractory to lenalidomide in all patients, and refractory to both bortezomib and lenalidomide in 3 patients. Six patients were previously exposed to anti-CD38 mAb. Eleven (73%) patients had presence of high-risk cytogenetics including del 17p, t (4;14), t (14;16) and 1q gain/amp. All 6 patients in in the safety lead-in cohort completed at least 2 cycles of treatment (DLT window), while the remaining patients completed at least 1 cycle of treatment. The median follow up was 8.5 months (1-16.6). None of the patients experienced DLT in the safety lead-in phase. Grade 3-4 treatment emergent adverse events (TEAEs) occurred in 15 (100%) of patients with most common being lymphopenia (93%), neutropenia (93%) and leucopenia (40%). Grade 3-4 infections occurred in 1(7%) patient. No grade 5 TEAEs occurred. Infusion related reactions occurred in 1 patient, maximum grade 2. All patients were evaluable for response with an ORR of 80% (12/15) (6 VGPR or better, 6 PR), and 100% in anti-CD38 mAb naive. The 12-month PFS rate was 67% (45%-99%). 5 patients discontinued the study (4 due to disease progression and 1 withdrew consent). Lymphocyte subpopulations showed a decrease in relative and absolute NK cells and an increase in monocytes (Figure 1 A, B). NK cell cytolytic activity was maintained in patient samples obtained over the course of the study (Figure 1C).
Conclusions: This is the first ever report combining two different mAbs with dual targeting of CD38 and SLAMF7 in RRMM. The results demonstrate that Isa-EloPD combination is both safe and feasible with high frequency and durability of responses. Despite an anticipated reduction in number, NK cell cytotoxicity remain unaffected with the combination. The study is ongoing and results from additional patients and longer follow up will be presented.
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Birmingham, AL
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