A Study of the Efficacy and Safety of BCD-248 in Combination With Daratumumab in Patients With Relapsed or Refractory Multiple Myeloma (AMMADINA)

Prior treatment

• Prior therapy with anti-BCMA or anti-CD3 drugs, pomalidomide.
• Refractory to anti-CD38 monoclonal antibodies according to the IMWG criteria.
• Use of any investigational products or medical devices within 28 days prior to randomization or planned use of investigational products or medical devices during participation in this study.
• Hematopoietic stem cell transplantation - prior to randomization or planned during the study
• Plasmapheresis within 14 days prior to randomization.
• Administration of a live attenuated vaccine within 28 days prior to randomization.
• A history of myelodysplastic syndrome or other malignancies other than multiple myeloma within 5 years prior to screening.
• Concomitant diseases and/or conditions that significantly increase the risk of AEs during the study:
  • Stable angina pectoris, functional class III-IV.
  • Unstable angina pectoris and/or myocardial infarction within 6 months prior to randomization.
  • Congestive heart failure, NYHA class III-IV.
  • Clinically significant (according to the Investigator) cardiac arrhythmia and conduction disorders that do not respond to the maximum possible antiarrhythmic therapy (therapy must be stable for 4 weeks before the planned start of the study therapy).
  • Moderate to severe asthma, uncontrolled asthma, asthma with forced expiratory volume in 1 second \<50% of predicted normal.
  • Chronic obstructive pulmonary disease with forced expiratory volume in 1 second \<50% of predicted normal.
  • A history of angioneurotic edema, severe respiratory failure.
  • Active autoimmune diseases. Patients with type 1 diabetes mellitus and hypothyroidism, requiring only hormone replacement therapy, as well as with skin diseases (vitiligo, alopecia, psoriasis, etc.), which do not require systemic therapy, are allowed to participate.
  • Thromboembolic (deep vein thrombosis, pulmonary embolism) or cerebrovascular (stroke, transient ischemic attack) events within 6 months prior to randomization.
  • Any infection within 14 days prior to randomization that requires systemic etiological therapy or may, in the Investigator's opinion, increase the risk of infectious complications.
  • Any other concomitant disease or condition, which, in the Investigator's opinion, significantly increases the risk of AEs in the study.
• Major surgery within less than 14 days prior to the expected start of the study therapy, incomplete recovery from surgery, or planned surgery during participation in the study.
• Pregnancy or breastfeeding, as well as intention to become pregnant or father a child during the study period and within 180 days after receiving the last dose of the IP.

Other illness

• Life-threatening acute complications of the underlying disease.
• Subjects with amyloidosis, POEMS syndrome, plasma cell leukemia
• HIV infection, active HBV infection, hepatitis C.
• Hypersensitivity, allergy, or intolerance to monoclonal antibodies or any component of BCD-248, daratumumab, pomalidomide, or dexamethasone.

Other

• CNS involvement or clinical signs of meningeal involvement of multiple myeloma.

• Signed informed consent form.
• Age ≥18 years.
• Documented diagnosis of multiple myeloma according to the IMWG criteria.
• Measurable disease at screening.
• At least 1, but not more than 3 prior lines of antimyeloma therapy, including lenalidomide and a proteasome inhibitor.
• Documented progression according to the IMWG criteria during or after the last line of therapy.
• ECOG score 0-2.
• Resolution of symptoms of toxicity on the prior line of therapy.