Phase II Study of Nivolumab (ONO-4538/BMS-936558) for Esophageal Cancer: Clinical activity by PD-L1 expression analysis

Abstract

Background: Since no other standard chemotherapy for esophageal cancer if a patient who is refractory or intolerant to standard therapies including combination therapy with cisplatin and 5‐FU (FP therapy), investigation of a novel drug is in higher demand. Nivolumab, a human monoclonal antibody to human programmed cell death‐1 (PD‐1), inhibits the binding of PD‐1 to PD‐1 ligand to enhance proliferation and activation of antigen‐specific T‐cells. Hence we explored the relationship between efficacy of nivolumab and PD‐L1 expression levels. Methods: We investigated the efficacy and safety of nivolumab in Japanese patients with unresectable, recurrent esophageal cancer who are refractory or intolerant to the standard therapy. Patients received nivolumab 3 mg/kg IV Q2W until progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) evaluated by independent review committee according to RECIST 1.1 while the relationship between PD‐L1 expression levels and efficacy was also explored. Results: We enrolled 65 patients and treated. A past report indicated that 11 (17.2%) of 64 patients had ORR (CR/PR, 1/10) as of the data cut on May 17, 2015. With regard to the report, immunohistochemistry assay was performed on pretreatment tumor biopsies from 37 patients. ORR (95% CI) for PD‐L1 positive >1%, >5% and‐10% patients was 23.8% (10.6, 45.1), 38.5% (17.7, 64.5), 33.3% (12.1, 64.6) and PD‐L1 negative <1%,<5% and <10% patients was 12.5% (3.5, 36.0), 8.3% (2.3, 25.8), 14.3% (5.7, 31.5). Conclusions: Nivolumab has meaningful activity and a manageable safety profile in pretreated esophageal cancer. Although no definitive conclusion was made due to the limited number of the provided tumor tissues, we obtained data potentially applicable to confirm a correlation between PD‐L1 expression levels and efficacy. We will confirm the detail relationship between PD‐L1 expression levels and efficacy in the ongoing phase III study with esophageal cancer.