Updated results for the advanced esophageal carcinoma cohort of the phase Ib KEYNOTE-028 study of pembrolizumab (MK-3475).

Abstract

7 Background: PD-L1 and PD-L2 expression have been associated with poor prognosis in esophageal cancer. Pembrolizumab (pembro) is a humanized monoclonal antibody against PD-1 that blocks interaction with PD-L1 and PD-L2. The multicohort, phase Ib KEYNOTE-028 (NCT02054806) trial was designed to evaluate the safety and efficacy of pembro in patients (pts) with PD-L1+advanced solid tumors. We report updated results from the esophageal carcinoma cohort of this study. Methods: Key eligibility criteria included advanced squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction, PD-L1 expression in tumor or stroma determined centrally by IHC, failure of standard therapy, and ECOG PS 0-1. Pts received pembro 10 mg/kg every 2 wk for up to 2 y or until confirmed progression, intolerable toxicity, or investigator decision. Response was assessed every 8 wk for the first 6 mo and every 12 wk thereafter. Primary end point was ORR per RECIST v1.1 by investigator review. Results: Of the 23 pts enrolled, median age was 65 y, 82.6% were men, 73.9% had squamous histology, and 87.0% received ≥ 2 prior therapies for metastatic disease. As of the Aug 4, 2015 data cutoff date, median follow-up duration was 31 wk (range 5.7-71). Nine pts (39.1%) had drug-related adverse events (DRAEs), most commonly decreased appetite (n = 3, 13.0%). Four pts (17.4%) had grade 3 DRAEs, with only decreased lymphocytes reported in > 1 pt (n = 2, 8.7%). No pts died or discontinued pembro due to a DRAE. Immune-mediated AEs, regardless of attribution by investigator, were grade 2 hypothyroidism (n = 2, 8.7%) and adrenal insufficiency (n = 1, 4.3%). ORR was 30.4% (95% CI 13.2-52.9), and the stable disease rate was 13.0% (n = 3, 95% CI 2.8-33.6); 6-mo and 12-mo PFS rates were 30.4% and 21.7%. Five of 7 responses were ongoing at data cutoff, with a median duration of response of 40.0 wk (range 24.1+ to 46.1+). Analysis of the relationship between PD-L1 expression level and antitumor activity is ongoing. Conclusions: Pembro continued to show manageable toxicity and durable antitumor activity in pts with heavily pretreated, PD-L1+ advanced esophageal carcinoma. Phase II and III trials of pembro in pts with esophageal carcinoma are ongoing. Clinical trial information: NCT02054806.