Background: Patients (pts) with cHL who relapse after autologous stem-cell transplant (ASCT) or progress after brentuximab vedotin (BV) have a poor prognosis. The PD-1 ligands PD-L1 and PD-L2 are frequently overexpressed in R/R cHL. Pembrolizumab is a humanized monoclonal antibody against PD-1 preventing binding to PD-L1 and PD-L2. In the phase 1b KEYNOTE-013 study, pembrolizumab demonstrated high antitumor activity (ORR = 65%) in heavily pretreated cHL pts. KEYNOTE-087 (NCT02453594) is a multicohort phase 2 study designed to confirm clinical activity of pembrolizumab in cHL pts. Methods: The study has 3 cohorts: R/R cHL after ASCT and subsequent BV therapy (cohort 1); ineligible for ASCT due to chemo-resistance (no response to salvage chemotherapy) and BV therapy failure (cohort 2); R/R cHL after ASCT but not treated with BV after ASCT (cohort 3). Pts receive pembrolizumab at a fixed dose of 200 mg IV Q3W. Primary end point is ORR, with response assessed every 12 wk according to Revised Response Criteria for Malignant Lymphomas. Prespecified interim analysis, based on investigator-assessed response, was performed after 30 pts reached first response assessment in cohorts 1 and 2. Results: At time of data cutoff (Feb 1, 2016), 60 pts were evaluable for cohorts 1 and 2. Median (range) age was 36 (19-64) years in cohort 1 and 33 (20-71) in cohort 2. 67% received ≥ 4 prior lines of therapy, and by design 100% failed prior BV. ORR among 30 pts in cohort 1 is 70% (95% CI, 51-85). 6 pts (20%) achieved CR (residual mass permitted if PET negative), 15 (50%) PR, and 6 (20%) stable disease as best response. ORR among 30 pts in cohort 2 is 80% (95% CI, 61-92). 8 pts (27%) achieved CR, 16 (53%) PR, and 4 (13%) stable disease as best response. With a median of 6 treatment cycles, most common treatment-related AEs in the combined cohorts are pyrexia (13%), diarrhea (8%), fatigue, back pain, platelet count decrease, dry skin, and cough (7% each). Conclusions: PD-1 blockade with pembrolizumab shows early responses in heavily pretreated cHL pts. Of note, pembrolizumab shows an unprecedented high ORR (80%) in pts who were not candidates for ASCT and failed previous BV therapy. Cohort 3 continues accrual and interim analysis results will be presented. Clinical trial information: NCT02453594