Clinical trial NCT06296121: A Study of the Efficacy and Safety of Monotherapy With BCD-264 and Darzalex in Subjects With Relapsed and Refractory Multiple Myeloma
Official title: A Double-Blind, Randomized Clinical Study of the Efficacy and Safety of Monotherapy With BCD-264 and Darzalex® in Subjects With Relapsed and Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Multiple Myeloma
Lead sponsor: Biocad
Sponsor class: INDUSTRY
First posted: 2024-03-06
Enrollment: 252
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 criteria: 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.

Primary outcomes:
measure: Overall response rate according to IMWG (International Myeloma Working Group) criteria
timeFrame: up to 24 weeks
Secondary outcomes:
measure: Stringent complete response rate according to IMWG criteria
timeFrame: up to 3 years
measure: Complete response (CR) rate according to IMWG criteria
timeFrame: up to 3 years
measure: Very good partial response (VGPR) rate according to IMWG criteria
timeFrame: up to 3 years
measure: Duration of response
timeFrame: up to 3 years
measure: Progression-free survival
timeFrame: up to 3 years
measure: Time to progression
timeFrame: up to 3 years
measure: Time to response
timeFrame: up to 3 years
measure: Overall survival
timeFrame: up to 3 years
Other outcomes:
measure: Incidence and characteristics of adverse events
timeFrame: up to 2 years
measure: Proportion of subjects with BAbs/Nabs
timeFrame: up to 2 years
measure: Time to BAb/NAb development
timeFrame: up to 2 years
measure: AUC0-168
timeFrame: up to Day 8 Cycle 1 (each cycle is 28 days)
measure: AUC0-∞
timeFrame: up to Day 15 Cycle 6 (each cycle is 28 days)
measure: AUC0-336, ss
timeFrame: from Day 1 to Day 15 Cycle 6 (each cycle is 28 days)
measure: Cmax
timeFrame: up to Day 15 Cycle 6 (each cycle is 28 days)
measure: Cmax, ss
timeFrame: up to Day 15 Cycle 6 (each cycle is 28 days)
measure: Tmax
timeFrame: up to Day 15 Cycle 6 (each cycle is 28 days)
measure: T1/2
timeFrame: up to Day 15 Cycle 6 (each cycle is 28 days)
measure: Vd
timeFrame: up to Day 15 Cycle 6 (each cycle is 28 days)
measure: Ctrough, ss
timeFrame: up to Day 15 Cycle 6 (each cycle is 28 days)
Locations:
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Clinical Hospital
city: Ekaterinburg
country: Russian Federation
facility: Sverdlovsk Regional Clinical Hospital No. 1
city: Kemerovo
country: Russian Federation
facility: Kuzbass Regional Clinical Hospital named after S.V. Belyaev
city: Krasnoyarsk
country: Russian Federation
facility: Regional Clinical Hospital
city: Moscow
country: Russian Federation
facility: Moscow City Clinical Hospital 52
city: Moscow
country: Russian Federation
facility: S.P. Botkin Moscow City Clinical Hospital
city: Saint Petersburg
country: Russian Federation
facility: Almazov National Medical Research Centre
city: Saint Petersburg
country: Russian Federation
facility: N.N. Petrov National Medicine Research Center of oncology
city: Saint Petersburg
country: Russian Federation
facility: Russian Research Institute of Hematology and Transfusiology of the Federal Medical and Biological Agency
city: Saint Petersburg
country: Russian Federation
facility: St Petersburg State I.P. Pavlov Medical University
city: Saint Petersburg
country: Russian Federation
facility: State budgetary healthcare institution Leningrad Regional Clinical Hospital
city: Samara
country: Russian Federation
facility: Samara State Medical University
city: Sochi
country: Russian Federation
facility: Oncological dispensary No. 2 of the Ministry of Health of the Krasnodar Territory
city: Ufa
country: Russian Federation
facility: Bashkir State Medical University
Study officials:
References: