The BCD-248-1 clinical study will evaluate the safety, pharmacokinetics, pharmacodynamics, and immunogenicity parameters of BCD-248 monotherapy in subjects with relapsed/refractory multiple myeloma and determine the optimal dosing regimen to be recommended for the second phase clinical study of BCD-248 in patients who:
Are aged 18 years or older.
Have a body weight of 50 to 100 kg.
Have a documented diagnosis of multiple myeloma in accordance with the IMWG diagnostic criteria1 (measurable disease determined by an M-gradient of the serum (SPEP2 ≥5 g/L), urine (UPEP3 ≥200 mg/24 h) or free light chain (FLC) secretion with an abnormal ratio with the concentration of the involved FLC of greater than 100).
Have a disease progressing during or after at least 2 lines of standard therapy, including a proteasome inhibitor, an immunomodulatory drug, a CD384-targeted therapy, with refractoriness5 to these classes of drugs.
The clinical study protocol requires an aspiration biopsy of the bone marrow as part of the study.
This clinical study has exclusion criteria (precluding participation in this clinical study), which will all be explained to the potential participant by the study doctor. In particular, the exclusion criteria are:
Prior treatment with BCMA6-targeted therapy or another CD37-targeted therapy.
Prior antitumor therapy, including chemotherapy, targeted therapy, immunotherapy, radiotherapy, use of drugs or medical devices studied in other clinical studies, within 4 weeks prior to the first dose of BCD-248.
Glucocorticoid therapy at a cumulative dose equivalent to ≥140 mg of prednisolone within 2 weeks prior to the first dose of BCD-248.
Hematopoietic stem cell transplantation (HSCT): allogenic HSCT within 6 months prior to the first dose of BCD-248 and/or symptoms of acute or chronic GVHD; autologous HSCT within 3 months prior to the first dose of BCD-248.
CNS involvement or clinical signs of meningeal involvement due to multiple myeloma.
Active autoimmune diseases (subjects with type 1 diabetes mellitus and hypothyroidism requiring only hormone replacement therapy, as well as with skin diseases (vitiligo, alopecia, or psoriasis), which do not require systemic therapy, are allowed to participate).
Moderate to severe asthma, grade 3-4 chronic obstructive pulmonary disease, severe respiratory failure.
Grade ≥4 allergic, infusion reactions, grade ≥3 cytokine release syndrome during previous treatment with antitumor biological drugs.
Hypertension not controlled by antihypertensive drugs at the target BP level (SBP <140 mmHg or DBP <90 mmHg).
Acute coronary syndrome within 6 months prior to the first dose of BCD-248, or class 3-4 (according to the Canadian Cardiovascular Society) stable angina pectoris, or NYHA class 3-4 congestive heart failure.
Clinically significant (according to the investigator) cardiac arrhythmia and conduction disorders that do not respond to the maximum possible antiarrhythmic therapy (therapy should be stable for 4 weeks before the first dose of BCD-248).
Established HIV infection, active hepatitis B, active hepatitis C.
Impossibility of intravenous administration of drugs, intravenous contrast enhancement.
Hypersensitivity or allergy to any of the components of BCD-248, to drugs obtained using Chinese hamster ovary cells.
Pregnancy or breastfeeding, planned pregnancy or fatherhood throughout the study and for 6 months after the last dose of BCD-248.
The BCD-248-1 clinical study takes place at study centers in Saint Petersburg and Moscow, Russian Federation.
You can ask questions about participation in the clinical study and request contact information about study centers using a special form «Do you have any questions?».
The study doctor will tell the potential participant about other eligibility criteria and contraindications for participation in this clinical study. The potential participant should read the full information about the clinical study and consult the study doctor and/or attending physician.
Authorization of the Ministry of Health of the Russian Federation for this clinical study, No. 737 dated December 30, 2022, and the list of approved study centers have been published in the State Register of Medicines.
IMG (International Myeloma Working Group) consensus criteria of disease progression and relapse.
SPEP, Serum Protein Electrophoresis.
UPEP, Urine Protein Electrophoresis.
CD38, cluster of differentiation 38.
Refractoriness is the inability of a cell to respond to a nerve impulse, which manifests itself in the absence of excitation following a stimulus due to a change in the state of voltage-gated channels in the membrane.
BCMA is a cell membrane protein involved in the differentiation and maturation of B-lymphocytes to plasma cells.
CD3 (cluster of differentiation 3) is a protein complex and coreceptor of T cells that participates in the activation of both cytotoxic T cells (CD8+ naive T cells) and T helper cells (CD4+ naive T cells).