Ramucirumab Plus Pembrolizumab in Previously Treated Advanced Gastroesophageal Cancer, NSCLC, and Urothelial Carcinoma


Key Points

  • The combination of ramucirumab and pembrolizumab had a manageable toxicity profile.
  • Evidence of antitumor activity was observed in all cohorts.

Results from a phase IB trial expansion stage reported in The Lancet Oncology by Herbst et al showed the combination of ramucirumab plus pembrolizumab had manageable toxicity and antitumor activity in previously treated advanced gastroesophageal cancer, non–small cell lung cancer (NSCLC), and urothelial carcinoma cohorts.

Study Details

After a phase IA safety run in period, patients with gastric or gastroesophageal junction adenocarcinoma (n = 41), NSCLC (n = 27), and urothelial carcinoma (n = 24) from 16 sites in the United States, France, Germany, Spain, and the United Kingdom were treated between July 2015 and June 2016 with pembrolizumab 200 mg on day 1 and ramucirumab 10 mg/kg on day 1 every 3 weeks; for 24 patients in the gastroesophageal cohort, ramucirumab was given at 8 mg/kg on days 1 and 8 every 3 weeks. Treatment continued until disease progression or other discontinuation criteria were met.

Median follow-up was 32.8 months.


Objective response was observed in three patients (7%) in the gastroesophageal adenocarcinoma cohort, eight patients (30%) in the NSCLC cohort, and three (13%) in the urothelial carcinoma cohort. Stable disease was observed in an additional 44%, 56%, and 38% of patients, respectively.

Adverse Events

Overall, treatment-related adverse events of any grade occurred in 75 patients (82%), with the most common being fatigue (36%). Treatment-related grade 3 or 4 adverse events occurred in 24% of patients, with the most common being hypertension (7%) and colitis (5%). Serious adverse events occurred in 58% and were considered related to treatment in 24%, with the most common treatment-related events being abdominal pain in patients with gastroesophageal adenocarcinoma (7%); asthenia (7%) and myocardial infarction (7%) in patients with NSCLC; and colitis (8%) in patients with urothelial carcinoma. Treatment-related adverse events led to treatment discontinuation in 7% of patients. One death (due to pulmonary sepsis in a patient with gastroesophageal adenocarcinoma) was considered related to treatment.

The investigators concluded, “Ramucirumab in combination with pembrolizumab showed a manageable safety profile with favorable antitumour activity in patients with previously treated advanced gastric or gastroesophageal junction adenocarcinoma, NSCLC, and urothelial carcinoma. Our results contribute to the growing evidence that supports dual inhibition of the vascular endothelial growth factor (VEGF)/VEGFR2 and [programmed cell death protein 1/ligand 1] pathways. This combination could be further explored with or without chemotherapy, especially for patients with tumours for which single-agent checkpoint inhibitors have shown no additional benefit over chemotherapy.”

Roy S. Herbst, MD, of Yale Cancer Center, Yale School of Medicine, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Eli Lilly and Company and Merck and Co. For full disclosures of the study authors, visit

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