CHICAGO, IL—The anti–PD-1 monoclonal antibody, pembrolizumab (MK-3475), demonstrated promising antitumor activity in advanced gastric cancer, results from the KEYNOTE-012 study presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting have found.

Among patients who were PD-L1–positive, overall response rate (ORR), the primary end point, was 22.2% (95% CI: 10.1, 39.2) by central review and 33.3% (95% CI: 19.1, 50.2) by investigator review, reported Yung-Jue Bang, MD, of the Seoul National University College of Medicine in Seoul, South Korea.

Previously, pembrolizumab has demonstrated clinical activity in multiple tumor types, and is approved in several countries for advanced melanoma, he said.

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In this study, archival tumor samples from patients with recurrent or metastatic adenocarcinoma of the stomach or gastroesophageal junction were screened for PD-L1 expression using a prototype IHC assay with the 22C3 antibody and only those with PD-L1–positive tumors, defined as PD-L1 staining in stroma or 1% or more of tumor cells were eligible for the study.

Of the 162 patients screened, 65 (40%) were PD-L1–positive and 39 were enrolled, 19 from the Asia-Pacific region and 20 from the rest of the world. Median age was 63 years (range: 33-78 years). A total of 67% had received at 2 or more prior therapies for advanced disease (range: 0-5 prior therapies).

Pembrolizumab 10 mg/kg was administered every 2 weeks for up to 2 years or until complete response, disease progression, or unacceptable toxicity. Imaging was performed every 8 weeks. The primary efficacy end point was ORR (RECIST 1.1) by independent central review. Secondary end points included duration of response, progression-free survival (PFS), and overall survival (OS).

Median follow-up duration was 8.8 months (range: 6.2-12.6 months), with 13 patients (33%) remaining on therapy. Median time to response was 8 weeks (range: 7-16 weeks), with 4 of 8 responses ongoing at the time of data cutoff. The median duration of response was 40 weeks (range: 20+ to 48+ weeks).

The 6 month PFS rate was 26% and median PFS was 1.9 months (95% CI: 1.8, 3.5). The 6-month OS rate was 66% and median OS was 11.4 months (95% CI: 5.7, NR).

Five patients (12.8%) experienced grade 3/4 treatment-related adverse events (AEs) with an incidence greater than 3%, peripheral sensory neuropathy (grade 3, 1 patient), fatigue (grade 3, 2 patients), hypothyroidism (grade 3, 1 patient), pemphigoid (grade 3, 1 patient),  and pneumonitis (grade 4, 1 patient). There were no treatment-related deaths and no discontinuations due to treatment-related AEs, Dr. Bang said.

Preliminary evidence points to a relationship between PD-L1 expression and efficacy in the preselected population, Dr. Bang said, with a one-sided P-value of 0.01 for OS in the 38 evaluable patients. Data suggest a relatively low cutoff is sufficient to detect most responders.

These results support further study of pembrolizumab for advanced gastric cancer, Dr. Bang concluded. Two clinical trials are currently underway in this population, KEYNOTE-059, a phase 2 study of pembrolizumab monotherapy or in combination with chemotherapy, and KEYNOTE-061, a phase 3 study of pembrolizumab compared with paclitaxel as second-line therapy.


1. Bang Y-J, Chung H-C, Shankaran V, et al. Relationship between PD-L1 expression and clinical outcomes in patients with advanced gastric cancer treated with the anti-PD-1 monoclonal antibody pembrolizumab (MK-3475) in KEYNOTE-012. J Clin Oncol. 2015;33:(suppl; abstr 4001).