Avelumab (MSB0010718C; anti-PD-L1) in patients with recurrent/refractory ovarian cancer from the JAVELIN Solid Tumor phase Ib trial: Safety and clinical activity.

5533 Background: Avelumab* is a fully human anti-PD-L1 IgG1 antibody under clinical investigation in multiple cancers. We report safety and clinical activity of avelumab in patients (pts) with recurrent/refractory ovarian cancer (OC; NCT01772004). Methods: Pts with advanced OC unselected for PD-L1 expression received avelumab 10 mg/kg IV Q2W until progression, unacceptable toxicity, or withdrawal. Tumors were assessed every 6 wks (RECIST 1.1). Unconfirmed objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated. Adverse events (AEs) were graded by NCI-CTCAE v4.0. PD-L1 expression was assessed by immunohistochemistry. Results: As of Oct 23, 2015, 124 pts were treated with avelumab (median 12 wks [range 2-54]) and followed for a median of 54 wks (range 11-101). Median age was 62 y (range 27-84), ECOG PS was 0 (47.6%) or 1 (52.4%), and median number of prior therapies was 4 (range 1-13). Treatment-related (TR) AEs occurred in 82 pts (66.1%); most common (≥10%) were fatigue (13.7%), infusion-related reaction (12.1%), and diarrhea (11.3%), all of grade 1/2. Grade 3/4 TRAEs were reported in 8 pts (6.5%); of these, only increased lipase occurred in > 1 pt (n = 2). There were no treatment-related deaths. ORR was 9.7% (95% CI: 5.1-16.3) based on 12 partial responses; 6 were ongoing. Stable disease was observed in 55 pts (44.4%); disease control rate was 54.0%. PD-L1 expression was evaluable in 74 pts (59.7%). Using a ≥1% cutoff for tumor cell staining, 57/74 (77.0%) were PD-L1+ and ORR was 12.3% in PD-L1+ (7/57; 95% CI: 5.1, 23.7) vs 5.9% in PD-L1− pts (1/17; 95% CI: 0.1, 28.7). Overall, median PFS was 11.3 wks (95% CI: 6.1, 12.0) and median OS was 10.8 mos (95% CI: 7.0, 16.1). Conclusions: Single-agent avelumabshowed an acceptable safety profile and clinical activity in heavily pretreated pts with OC. These data represent the largest study of anti-PD(L)1 agents in pts with OC to date. The potential relationship between biomarkers, such as germline BRCA mutational status, and the probability of response is being investigated. Randomized phase 3 trials of avelumab in OC are underway. *Proposed INN. Clinical trial information: NCT01772004.