A phase Ib study of TAK-079, an investigational anti-CD38 monoclonal antibody (mAb) in patients with relapsed/ refractory multiple myeloma (RRMM): Preliminary results.

Abstract

8539 Background: TAK-079 is a subcutaneously (SC) administered mAb with multiple modes of action for killing target cells. Here we report data from an ongoing dose finding study of TAK-079 monotherapy in patients with RRMM (NCT03439280). Methods: Pt were eligible after ≥ 3 lines of therapy and previous exposure to immunomodulatory drug (IMiD), proteasome inhibitor (PI), alkylating agent, and corticosteroid; prior anti-CD38 therapy allowed. Patients were refractory or intolerant to at least 1 PI and 1 IMiD. TAK-079 given as a SC injection weekly for 8 doses, every other week for 8 doses, then monthly until disease progression (PD) or unacceptable toxicity. SC injection was 2 mL administered in ≤ 1 minute. Results: 34 patients were enrolled across 5 fixed dose cohorts (TAK-079 45-135-300-600-1200 mg SC) as of 09 December 2019. Median age was 65 (50–81) years. At study entry, 65% were refractory to both an IMiD and PI; 82% refractory to last line of therapy, 21% of patients were previously exposed to at least 1 anti-CD38 monoclonal antibody. Median number of prior therapies was 4 (2,12). No ≥ Grade 1 early or late systemic infusion reactions (IRR) reported. Three ( < 1%) injection site reactions described in > 1200 injections administered; 2 mild pruritis and 1 moderate swelling. Drug related adverse events (AEs), any grade, occurring in at least 10% of patients were: fatigue (21%), anemia (18%), neutropenia (18%), leukopenia (15%). Neutropenia was the only drug related grade 3 AEs in 2 or more patients (n = 2); only drug related SAE was 1 Grade 3 diverticulitis. No drug-related grade 4 AEs, AEs leading to study discontinuation, or on-study deaths reported. Recommended phase 2 dose (RP2) is to be 600 mg based on no reported DLTs, no MTD identified, and preliminary efficacy (PFS and response [ORR]). At the RP2 dose, 9 patients received at least 6 cycles of therapy by the data cutoff; their ORR was 33%, median duration of response was not estimable. The clinical benefit rate (minimal response or better) in all 12 patients enrolled at the RP2 dose was 67%. At a median follow-up of 7.5 months, PFS not estimable at the RP2 dose. Conclusions: TAK-079 monotherapy is safe, generally well tolerated, and active in patients with RRMM through tested doses. Clinical activity occurred early and was durable. With no MTD identified, no IRRs, no significant hematologic toxicity, the RP2 dose is 600 mg. PFS, with a median FU of 7.5 months at the data-cut off, is not estimable at the RP2 dose. Updated safety and efficacy data will be presented. Clinical trial information: NCT03439280 .

Monoclonal Antibodies to Treat Multiple Myeloma: A Dream Come True

“…Recent data on TAK-079 (mezagitamab) showed an ORR of 33% at the dose of 600 mg sc in heavily pretreated RRMM patients (4 median prior lines of therapy, including patients exposed to other anti-CD38 mAbs). Its advantages are the sc route of administration and a promising safety profile (no IRRs, no significant hematologic toxicity) [33].…”

Targeted Therapies for Multiple Myeloma

“…Additional anti-CD38 monoclonal antibodies (MOR202, TAK-079) have been examined in pre-clinical studies [ 57 ]. Phase 1/2 data exploring MOR202 and TAK-079 have recently been published, and further clinical evaluation is underway [ 58 , 59 ]. Overall, CD38 monoclonal antibodies have demonstrated reasonable but not spectacular single-agent efficacy in RRMM patients; however, their use in combination with established therapies appears to significantly improve response rates and survival.…”

Isatuximab and Belantamab Mafodotin: A Primer to an Evolving Multiple Myeloma Landscape

“…Differences among anti-CD38 moAb are highly dependent on the Fc-directed activity driven by location of epitope binding and subsequent anti-MM potency of the many immune mechanisms. There are currently four CD38 moAb therapies with Phase II or more clinical data (daratumumab, isatuximab, MOR, 15 and TAK-079 16 ). 10,17…”

“…Opportunities to improve patient care experiences with different CD38 moAb include recent approval of subcutaneous daratumumab administration, 37 isatuximab fixed-volume infusions reducing infusion duration to less than 2 hours, 38 reduced IRR moAb MOR-202, 15 and nonhyaluronidase-containing subcutaneous formulation of TAK-079. 16 Due to its efficacy and tolerability in the RRMM setting, there are several ongoing clinical trials investigating the efficacy of isatuximab in combination with both IMID and PI therapies in patients with NDMM. These include both transplant eligible 39 and transplant ineligible [40][41][42][43] patients.…”