Overview

The aim of this study is to confirm the comparability of the efficacy and safety profiles of BCD-264 and Darzalex as monotherapy for relapsed and refractory multiple myeloma in subjects previously treated with proteasome inhibitors and immunomodulatory drugs, and who had disease progression on prior therapy.

Eligibility

Inclusion Criteria:

1. Signed informed consent form.
2. Age ≥ 18 years at the time of signing of the informed consent form.
3. Documented diagnosis of multiple myeloma according to IMWG criteria
4. Measurable disease at screening:
   1. M-protein in serum ≥ 1.0 g/dL (10 g/L) or in 24-hour urine ≥ 200 mg; or
   2. light chain myeloma: serum "involved" FLC level ≥ 10 mg/dL (100 mg/L) and abnormal κ/λ FLC ratio .
5. At least a partial response according to IMWG criteria to at least 1 prior line of

   therapy.

6. Subjects with relapsed and refractory multiple myeloma who previously received therapy with proteasome inhibitors and immunomodulatory drugs, and who had disease progression on prior therapy
7. ECOG score 0-2.
8. Not pregnant and willing to use contraception.
9. Consent to bone marrow biopsy in the study.

Exclusion Criteria:

1. Prior treatment with daratumumab or other anti-CD38 therapy.
2. Prior treatment for multiple myeloma within 2 weeks or 5 half-lives before the date of randomization, except for a short course of glucocorticoids
3. Autologous hematopoietic stem cell transplantation within 12 weeks prior to the date of randomization.
4. Allogeneic hematopoietic stem cell transplantation, regardless of timing.
5. Scheduled hematopoietic stem cell transplantation prior to progressive disease during this study.
6. Plasma cell leukemia, POEMS syndrome or amyloidosis.
7. Waldenstrom macroglobulinemia or other concomitant diseases with hyperproduction of monoclonal IgM (M-protein) in the absence of clonal proliferation of plasma cells with lytic bone involvement.
8. A history of other malignancies within the last 5 years, with the exception of squamous cell and basal cell skin cancer, cervical, breast carcinoma in situ, or other non-invasive malignancies that, in the Investigator's opinion are considered to have been adequately treated and have a minimal risk of recurrence for 5 years.
9. Plasmapheresis within 28 days prior to randomization.
10. Clinical signs of meningeal involvement of multiple myeloma.
11. Pregnancy or breastfeeding, as well as planning pregnancy throughout the study and within 3 months after the last dose of daratumumab; for male subjects, planning to conceive a child throughout the study and within 3 months after the last dose of daratumumab.