Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with metastatic or locally advanced solid tumors: assessment of safety and tolerability in a phase I, open-label expansion study.

Abstract

3044 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 I, open-label, parallel-group expansion study (NCT01772004) was to assess the safety and tolerability of avelumab in patients (pts) with metastatic or locally advanced solid tumors. Methods: Pts with advanced or metastatic disease (including NSCLC, gastric, ovarian, breast, and melanoma; ECOG PS 0-1 at trial entry) were treated with avelumab at 10 mg/kg Q2W until confirmed complete response (CR), progression, unacceptable toxicity, or withdrawal. Adverse events (AEs) were evaluated by CTCAE v4.0. Results: In total, 480 pts treated with avelumab were followed-up for at least 4 weeks (wks) by Nov 5, 2014 and assessed in this interim analysis (median age, 60 years [range 29-85]; ECOG PS 0 [40.6%], 1 [59.0%], 3 [0.2%], or unknown [0.2%]; median of 2 prior treatments [range 1-≥ 4]). Drug-related treatment-emergent AEs (TEAEs; all grades) occurred in 68.8% of pts, with the most frequent being fatigue (20.2%), nausea (12.9%), infusion-related reaction (IRR) (9.8%), diarrhea (6.9%), chills (6.9%), decreased appetite (6.3%), pyrexia (5.6%), influenza-like illness (5.2%), and arthralgia (5.0%). Drug-related TEAEs resulted in treatment discontinuation in 34 pts; of these, 8 were due to an IRR. Drug-related grade ≥ 3 TEAEs were reported in 12.3% (n = 59); the most common of these were anemia (5), fatigue (5), increased GGT (4), IRR (4), increased lipase (4), and decreased lymphocytes (3). AEs that were potentially immune-related were observed in 11.7% of pts, with the most common being hypothyroidism (4.0%) and pneumonitis (1.5%). Conclusions: Avelumab demonstrated an acceptable safety profile in a heavily pretreated population across a range of tumor types. Development of avelumab as a monotherapy and in combination is ongoing. *Proposed INN. Clinical trial information: NCT01772004.