9549 Background: MIRACULUM (NCT03269565) is a multicenter open-label parallel-arm phase II study investigating the antitumor activity of BCD-100, an IgG1 anti-PD-1 monoclonal antibody with Fc silencing “LALA” mutation, in patients with advanced melanoma. Interim analysis at 6-months is presented. Methods: Patients (pts) with unresectable or metastatic melanoma, without autoimmune disease, and no prior anti-PD-1 or anti-CTLA-4 therapy were eligible. Pts received BCD-100 1 mg/kg Q2W (arm 1) or BCD-100 3 mg/kg Q3W (arm 2) until disease progression or intolerable toxicity. Primary endpoint was ORR assessed per irRECIST by independent central radiology review. A statistical hypothesis that BCD-100 has significant anti-tumor effect (ORR more than 28% in per protocol population) was tested for each study arm with alpha 0.05 and 80% power. Results: 126 pts were treated and 114 were evaluable for the primary endpoint (9 pts dropped out before their first efficacy assessment and 3 pts had major protocol deviations). In arm 1 and arm 2, 17 (27%) and 16 (25%) pts received prior treatment for advanced disease, respectively. The study met its primary endpoint in both study arms. In arm 1, 34% ORR was achieved among 59 response-evaluable patients, including 4 CR and 16 PR, and the disease control rate (DCR) was 68%. In arm 2, 29% ORR was achieved among 55 response-evaluable pts, including 2 CR and 14 PR, and the DCR was 55%. All responses were durable; only one patient in arm 1 presented disease progression, and median PFS and OS were not reached in either study arms at 6 months follow-up. Treatment-related AEs (TRAEs) occurred in 48% of pts in each study arm, including 6% and 5% with grade 3/4 TRAEs in arm 1 and 2, respectively. Immune-related AEs (irAEs) occurred in 29% of pts in arm 1 and 30% of pts in arm 2, including 3% of pts with grade 3/4 irAEs in each arm. Conclusions: Both dosing regimens of BCD-100 (1 mg/kg Q2W and 3 mg/kg Q3W) have durable antitumor activity and a manageable safety profile in patients with advanced melanoma. Clinical trial information: NCT03269565.
BackgroundBCD-057 is an adalimumab biosimilar candidate manufactured by BIOCAD, Russia. Full spectrum of physicochemical and preclinical studies showed equivalence of BCD-057 to innovator drug Humira (reference adalimumab, rADA).ObjectivesTo establish the equivalence of pharmacokinetics and absence of differences in safety of BCD-057 and rADA after the single subcutaneous injection in healthy volunteers.Methods94 healthy volunteers were enrolled into the study. 10 of them withdrew consent before drug administration and were not included in analysis. All patients were randomly assigned into 2 groups in a ratio of 1:1 to receive a single subcutaneous injection of BCD-057 or rADA at a dose of 40 mg. The primary endpoints were Cmax and AUC0–∞ after the single adalimumab injection. The secondary PK endpoints included AUC0–1680 h, Tmax, T1/2, Vd, Kel, CL. Adalimumab serum concentrations were evaluated immediately before the injection and after 6, 24, 48, 72, 96, 120, 144, 168, 192, 336, 672, 1008, 1440 and 1680 hours after it. Safety and immunogenicity were also assessed during the study.ResultsPharmacokinetic (PK) analysis demonstrated that 90% CI for the ratio of geometric means of Cmax of adalimumab after single injection of BCD-057 or rADA was 87.48–111.84%. 90% CI for the ratio of geometric means of AUC0-∞ lied within 87.90–117.22%. Both of these facts confirm the bioequivalence of BCD-057 and rADA. There were no statistically significant differences between the groups for all other secondary PK parameters. BCD-057 and rADA were well tolerated. No SAEs were observed during the study. AEs were observed in 9 (22.5%) healthy volunteers in BCD-057 group and in 14 (31.8%) volunteers in rADA group (p=0.463, Fisher's exact test [two-tailed]). They were presented by laboratory abnormalities including leucopenia, neutropenia, monocytosis, monocytopenia, increase in total bilirubin, ALT and AST. All AEs were mild (Grade 1 [CTCAE 4.03]), transient and were not associated with any clinical symptoms. 27 (67.5%) subjects in BCD-057 group and 33 (75.0%) subjects in rADA group (p=0.478, Fisher's exact test [two-tailed]) developed anti-adalimumab antibodies. Neutralizing antibodies to adalimumab were found in 2 (5.0%) volunteers in BCD-057 group and in 5 (11.4%) volunteers in rADA group (p=0.437, Fisher's exact test [two-tailed]).ConclusionsPK, safety and immunogenicity of BCD-057 and rADA after a single subcutaneous administration in healthy volunteers are considered to be equivalent. These data allow to proceed to the subsequent BCD-057 study aimed to assess efficacy and safety in patients with moderate-to-severe plaque psoriasis.Referencesfinal study report on phase 1 clinical study of BCD-057 in healthy volunteers. Clinical trial information: NCT02395055.Disclosure of InterestA. Eremeeva Employee of: CJSC BIOCAD, S. Fogt Employee of: CJSC BIOCAD, E. Chernyaeva Employee of: CJSC BIOCAD, A. Kushakova Employee of: CJSC BIOCAD, T. Ostroukhova Employee of: CJSC BIOCAD, R. Ivanov Employee of: CJSC BIOCAD
Широкое внедрение в клиническую практику биологических препаратов на основе моноклональных антител в последнее десятилетие ознаменовало новую веху в истории медицины-появление таргетных молекул с наибольшей избирательностью действия. Возможности, связанные с их использованием, обусловили лавинообразный рост потребности в этих препаратах. Наиболее
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