Results of a Double-Blind Prospective Comparative Randomized Phase 3 Clinical Trial of the Efficacy and Safety of BCD-264 and Darzalex as Monotherapy for Relapsed/Refractory Multiple Myeloma (BCD-264-2/DARVIVA)

AIM. To confirm the comparability of the biosimilar daratumumab BCD-264 (BIOCAD) with the reference drug Darzalex (Johnson & Johnson) in terms of efficacy and safety of the monotherapy for relapsed/refractory (r/r) multiple myeloma (MM). MATERIALS & METHODS. This paper is based on the double-blind prospective comparative randomized phase 3 clinical trial BCD-264-2/DARVIVA assessing the efficacy and safety of BCD-264 and Darzalex as monotherapy for r/r MM. Duration of the blind period was 24 weeks. The trial enrolled 252 r/r MM patients treated with proteasome inhibitors and immunomodulatory drugs. This paper documents the analysis of the data collected within the blind period when the therapy was administered to Group 1 and Group 2, whereby neither the investigators nor the patients knew which drug is being used in each of the groups. RESULTS. The primary end point of the study was overall response rate (ORR) in 24 weeks after therapy onset. In Group 1, ORR was 36.2 % and it was 32.0 % in Group 2; ORR ratio for Group 1/2 was 1.13 (95% confidence interval [95% CI] 0.80–1.60) and 0.88 (95% CI 0.63–1.24) for Group 2/1. This confirmed the hypothesis of BCD-264 being no less effective than Darzalex. Besides, an additional hypothesis of drug equivalence was proved true demonstrating also the comparability of the drugs across all secondary efficacy end points and safety parameters. The most common adverse events reported in both groups were leukopenia, neutropenia, lymphopenia, anemia, thrombocythemia, infusion-associated reactions, and pneumonia. CONCLUSION. Both drugs BCD-264 and Darzalex showed comparable efficacy and safety during the 24-week period in the BCD-264-2/DARVIVA trial as well as comparable immunogenicity and pharmacokinetic profile.