Antitumor activity and safety of pembrolizumab in patients (pts) with PD-L1 positive advanced ovarian cancer: Interim results from a phase Ib study.

5510 Background: Pembrolizumab is a potent, highly selective humanized monoclonal antibody against PD-1 designed to block interaction with PD-L1 and PD-L2 and remove the inhibition of T-cell activation against cancer. PD-L1 was found to be overexpressed in ovarian cancer and can contribute to malignancy. We assessed the safety and efficacy of pembrolizumab in pts with PD-L1+advanced ovarian cancer. Methods: KEYNOTE-028 (NCT02054806) is a nonrandomized, multicohort phase Ib trial of pembrolizumab in pts with PD-L1+ advanced solid tumors. Key eligibility criteria for the ovarian cancer cohort included advanced ovarian epithelial, fallopian tube, or primary peritoneal carcinoma; failure of prior therapy; PD-L1 expression in ≥ 1% of cells in tumor nests or PD-L1+ bands in stroma as determined by a prototype IHC assay at a central laboratory; and ECOG PS 0-1. Pembrolizumab 10 mg/kg was given every 2 weeks for up to 2 years or until confirmed progression or unacceptable toxicity. Primary end points: safety, tolerability, and preliminary efficacy. Response assessed per RECIST v1.1 by investigators every 8 weeks for the first 6 months and every 12 weeks thereafter. Results: 26 pts were enrolled. Mean (SD) age was 58.1 (7.5); 57.7% were white. 84.6% received prior therapies for recurrent/metastatic disease (38.5% received ≥ 5 therapies), and 50% received prior adjuvant therapies. One pt achieved complete response and 2 pts experienced partial response; 6 pts had stable disease. Of the 3 patients who responded, all remain in response with duration of response ≥ 24 weeks at the time of analysis. The best overall (confirmed) response was 11.5% (95% CI, 2.4-30.2). 6/26 (23.1%) had evidence of tumor reduction; 3 had a tumor reduction of at least 30%. All pts experienced ≥ 1 adverse event (AE) (regardless of treatment); most common were fatigue (42.3%), anemia (30.8%), and decreased appetite (30.8%). Drug-related AEs occurred in 69.2% of pts (grade ≥ 3, 1/26 pts). Currently, 6 pts remain on pembrolizumab treatment. Conclusions: PD-1 blockade with pembrolizumab is well tolerated and has antitumor activity in pts with advanced ovarian cancer. This preliminary signal for clinical efficacy will be further investigated. Clinical trial information: NCT02054806.