Phase I open-label, multiple ascending dose trial of MSB0010718C, an anti-PD-L1 monoclonal antibody, in advanced solid malignancies.

3064 Background: MSB0010718C is a fully human IgG1 monoclonal antibody targeting the coregulatory protein Programmed Death (PD)-Ligand 1 (PD-L1). PD-1/PD-L1 interactions induce T-cell anergy, protecting tumor cells from elimination by the immune system. MSB0010718C is expected to have antitumor activity by restoring immune system activity and through ADCC. Objectives: Assess the safety of MSB0010718C and determine its maximum tolerated dose, and analyze its pharmacokinetic (PK) profile and target receptor occupancy (RO). Methods: Twenty-seven patients (pts) with refractory malignancies have been enrolled and treated to date. Dose escalation (3+3 design) has been performed for 4 dose levels (1, 3, 10, and 20 mg/kg, q2w). After dose-level safety was determined, accrual of additional pts was allowed in order to generate additional safety, PK, and RO data. Results: Four, 11, 6, and 6 pts have been accrued to dose levels 1–4, respectively. Median pt age is 64 years (range 34–77), ECOG 0–1, with a median of 2 prior lines of therapy for metastatic disease (range 0–5). Eleven pts received prior immunotherapy (range 1–2 lines). Twenty-three pts have been followed for at least 4 weeks by Jan 7, 2014. To date, 12 pts (52.2%) have come off study: 9 (39.1%) for progression, 2 (8.7%) for adverse events (AEs), and 1 (4.3%) for death. Grade ≥3 AEs attributable to drug comprised laboratory abnormalities in 3 pts (2 pts with grade 3 AEs; 1 pt with a grade 4 AE). One DLT was observed in 1 pt at dose level 4: an immune-related AE with creatine kinase increase, myositis and myocarditis. Data from 25 pts were evaluable for PK and RO analysis. Median time to maximum concentration for all doses was approximately 1.5 to 2 h after infusion, with a linear PK. Half-life was 63.4, 80.7, 93.9, and 115.1 h for dose levels 1, 2, 3, and 4, respectively, as measured by ELISA. Target RO data were available for 13 pts, as measured by PD-L1 binding on peripheral leukocytes via flow cytometry. Mean RO prior to second infusion was 75.7, 93.8, and 93.2% for dose levels 1, 2, and 3, respectively. Conclusions: MSB0010718C can be safely administered in doses up to 20 mg/kg IV every 2 weeks. Clinical trial information: NCT01772004.