BioCentury
ARTICLE | Clinical News

BNC105: Phase II data

March 24, 2014 7:00 AM UTC

Data from 136 evaluable patients with metastatic RCC who failed prior tyrosine kinase inhibitor (TKI) therapy in the Phase II portion of the open-label, dose-escalation, international Phase I/II DISRUPTOR-1 trial showed that IV BNC105 plus Afinitor everolimus (n=69) missed the primary endpoint of a greater proportion of patients who were progression-free at 6 months vs. Afinitor alone (n=67) (23 vs. 20 patients, p=0.6625). Median PFS was also similar between the BNC105 plus Afinitor arm and the Afinitor alone arm (4.7 vs. 4.1 months, p-value undisclosed). A subgroup analysis showed that in patients with liver metastases (n=26), BNC105 plus Afinitor led to a median PFS of 6.6 months vs. 2.8 months for Afinitor alone (p-value undisclosed). In patients with a previous nephrectomy (n=18), BNC105 plus Afinitor led to a median PFS of 7.1 months vs. 4.1 months for Afinitor alone (p-value undisclosed). In patients with Fuhrman Grade 2 histological differentiation grade tumors (n=30), BNC105 plus Afinitor led to a median PFS of 6.4 months vs. 4.1 months for Afinitor alone (p-value undisclosed).

Additionally, a pre-specified exploratory endpoint showed that changes in several plasma biomarkers - macrophage inflammatory protein-1 beta ( CCL4; MIP1B), CCL22 chemokine ligand 22 (CCL22; MDC), IL-1 beta, IL-12B, alpha-2-macroglobulin (A2M), beta-2 microglobulin (B2M) and serpin peptidase inhibitor clade A member 7 ( SERPINA7; TBG) - were significantly associated with PFS or lack thereof at 6 months following combination treatment. Patients received 16 mg/kg IV BNC105 on days 1 and 8 of a 21-day cycle plus once-daily 10 mg Afinitor. Patients who were progressing or who were intolerant to Afinitor monotherapy were allowed to receive BNC105 as a single agent. Bionomics previously reported data from 12 patients with metastatic RCC in the Phase I portion of the trial showing that BNC105 plus Afinitor led to 8 cases of stable disease (see BioCentury, Aug. 8, 2011 & June 17, 2013). ...