Pembrolizumab (MK-3475) for patients (pts) with advanced esophageal carcinoma: Preliminary results from KEYNOTE-028.

Abstract

4010 Background: Expression of the PD-1 ligands PD-L1 and PD-L2 has been associated with poor prognosis in esophageal cancer. Pembrolizumab is a highly selective humanized monoclonal antibody against PD-1 designed to block the interaction between PD-1 and PD-L1 and PD-L2. We assessed pembrolizumab safety and efficacy in pts with PD-L1+ esophageal carcinoma. Methods: KEYNOTE-028 (NCT02054806) is a nonrandomized, multicohort, phase Ib trial of pembrolizumab for PD-L1+ advanced solid tumors. Key eligibility criteria for this cohort included squamous cell carcinoma (SCC) or adenocarcinoma of the esophagus or gastroesophageal junction, measurable disease, PD-L1 expression in ≥ 1% of cells in tumor nests or PD-L1+ stromal bands determined centrally by IHC, failure of standard therapy, ECOG PS 0-1, and no autoimmune disease. Pembrolizumab 10 mg/kg is being given every 2 weeks for up to 2 years or until confirmed progression, unacceptable toxicity, or investigator decision. Response is assessed every 8 weeks for the first 6 months and every 12 weeks thereafter. Primary end points are safety, tolerability, and ORR per RECIST v1.1 by investigator review. Results: Of the 90 pts with esophageal cancer who were screened, 37 (41%) had PD-L1+ tumors. Of the 23 pts treated between March and December 2014, 83% were men and median age was 65. Histology was squamous in 77% of pts, adenocarcinoma in 18%, and mucoepidermoid in 5%. Eighty-seven percent of pts received ≥ 2 prior therapies for metastatic disease; all pts received ≥ 1 platinum-based therapy. Six pts (26%) experienced drug-related adverse events (DRAEs), including 2 (9%) who experienced grade 3 DRAEs. There were no grade 4 DRAEs, and no pts died or discontinued due to a DRAE. ORR (confirmed and unconfirmed) was 23% (n = 5); best response was stable disease in 18% (n = 4) and progressive disease in 59% (n = 13). One pt did not have response assessed at the time of analysis. Six pts, including all responders, remain on treatment. Conclusions: Pembrolizumab has an acceptable safety profile and provides promising antitumor activity in pts with heavily pretreated, PD-L1+ advanced esophageal carcinoma. These data support further study of pembrolizumab for pts with esophageal carcinoma. Clinical trial information: NCT02054806.