Phase II Trial (BCD-100-2/MIRACULUM) of the Novel PD-1 Inhibitor (BCD-100) in Patients with Advanced Melanoma.

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.