Abstract CT132: Safety of avelumab (MSB0010718C), an anti-PD-L1 antibody: updated analysis from the phase Ib JAVELIN Solid Tumor trial
Authors: Kelly Karen , Patel Manish , Infante Jeffrey R. , Iannotti Nicholas , Nikolinakos Petros , Leach Joseph , Wang Ding , Chandler Jason , Jerusalem Guy , Gurtler Jayne , Arkenau Henrik-Tobias , Bajars Marcis , von Heydebreck Anja , Speit Isabell , Heery Christopher R. , Gulley James L. 
Published: July 2016

Abstract
Background: The programmed death-1 receptor (PD-1) and its ligand (PD-L1) are key therapeutic targets in the reactivation of the immune response against multiple cancers. Avelumab* (MSB0010718C) is a fully human anti-PD-L1 IgG1 antibody currently being investigated in clinical trials. The primary objective of this phase Ib, open-label expansion study (NCT01772004) was to assess the safety and tolerability of avelumab in patients (pts) with locally advanced or metastatic (LA/M) solid tumors.
Methods: Pts from 16 different expansion cohorts (including NSCLC, gastric, ovarian, urothelial, and breast; ECOG performance status [PS] of 0-1 at trial entry) and unselected for PD-L1 expression were treated with avelumab at 10 mg/kg IV, Q2W until confirmed progression, unacceptable toxicity, or any criteria for withdrawal occurred. Adverse events (AEs) were graded by NCI-CTCAE v4.0.
Results: As of Aug 4, 2015, 900 pts were treated with avelumab and followed for ?4 wks. Median age was 62 years (range, 23-91), ECOG PS was 0 (39.1%), 1 (60.6%), or 2-3 (0.2%), and median number of prior lines of anticancer therapy was 2 (range, 1-13). Median duration of treatment with avelumab and number of administrations were 10.0 wks (range, 2-92) and 5 infusions (range, 1-43), respectively. Treatment-related (TR) AEs of any grade occurred in 585 pts (65.0%). Grade ?3 TRAEs occurred in 91 pts (10.1%). The most frequent (?0.5%) grade ?3 TRAEs were IRRs (n = 8, 0.9%), GGT elevation (n = 7, 0.8%), lipase elevation (n = 7, 0.8%), anemia (n = 7, 0.8%), and fatigue (n = 6, 0.7%). Seventy-five pts (8.3%) experienced potential immune-related (ir) TRAEs, with hypothyroidism (n = 34, 3.8%) and pneumonitis (n = 8, 0.9%) occurring most frequently (?0.5%). Grade ?3 potential irTRAEs were reported for 17 pts (1.9%); the most frequent (?0.3%) were autoimmune hepatitis (n = 4; 0.4%), colitis (n = 3; 0.3%), and pneumonitis (n = 3; 0.3%). TRAEs resulted in permanent treatment discontinuation for 64 pts (7.1%); 2.6% (n = 23) discontinued due to an IRR and 1.3% (n = 12) discontinued due to a potential irTRAE. TRAEs were considered the primary cause of death by the investigator for 4 pts (0.4%): radiation pneumonitis (1), autoimmune hepatitis (1), acute liver failure (1), and respiratory distress (1).
Conclusion: Single-agent avelumab shows an acceptable safety profile in a heavily pretreated population of pts with LA/M malignancies. To date, &gt;1,500 pts have been enrolled in the JAVELIN Solid Tumor clinical trial. Additional safety and efficacy analyses from this study are ongoing, and recruitment to several phase III trials is underway. *Proposed INN.
Citation Format: Karen Kelly, Manish Patel, Jeffrey R. Infante, Nicholas Iannotti, Petros Nikolinakos, Joseph Leach, Ding Wang, Jason Chandler, Guy Jerusalem, Jayne Gurtler, Henrik-Tobias Arkenau, Marcis Bajars, Anja von Heydebreck, Isabell Speit, Christopher R. Heery, James L. Gulley. Safety of avelumab (MSB0010718C), an anti-PD-L1 antibody: updated analysis from the phase Ib JAVELIN Solid Tumor trial. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT132.