Pembrolizumab/Ramucirumab Combo Active in Advanced Gastric/GEJ Adenocarcinoma

Ian Chau, MD

A novel combination regimen of ramucirumab plus pembrolizumab demonstrated modest activity in patients with previously treated gastric or gastroesophageal juncture (GEJ) cancer, according to a report at the Gastrointestinal Cancers Symposium in San Francisco.

Four of 41 patients had partial responses to treatment with pembrolizumab and 2 different doses of ramucirumab. Almost half of the patients achieved disease control, which included stable disease.

The median progression-free survival was 2 to 3 months in the 2 patient cohorts, who developed no new or unexpected adverse effects, reported Ian Chau, MD, consultant medical oncologist at the Royal Marsden Hospital in London.

“Some activity was observed in previously treated gastric and GEJ adenocarcinoma, but the data are immature for survival end points,” Chau and colleagues concluded in a poster presentation. “The study was amended to explore this combination in first line, and enrollment is ongoing.”

“Additional data from these cohorts, including first-line treatment, will guide the future development of this combination in gastric/GEJ adenocarcinoma,” Chau said.

Although angiogenesis and immunosuppression are hallmarks of tumor evolution and progression, few studies have evaluated treatment strategies that simultaneously target the 2 processes.

Four clinical trials of ramucirumab, a vascular endothelial growth factor receptor (VEGFR)-2 inhibitor, demonstrated prolonged survival in patients with advanced gastric/GEJ cancer. Trials of pembrolizumab, a monoclonal antibody against programmed death-ligand 1 (PD-L1), demonstrated improved survival in patients with non-small cell lung cancer (NSCLC) and melanoma, as well as promising activity in a number of other tumor types, including gastric/GEJ cancers, Chau and colleagues noted in the background information of their presentation.

An ongoing phase Ia/b clinical trial evaluated the addition of ramucirumab to pembrolizumab in patients with gastric/GEJ, NSCLC, urothelial carcinoma, or biliary tract cancer that had progressed on systemic therapy. The gastric/GEJ subgroup enrolled in 2 cohorts, 1 that received ramucirumab 8 mg/kg on days 1 and 8, and 1 that received 10 mg/kg on day 1. Both cohorts received pembrolizumab 200 mg every 3 weeks.

The gastric/GEJ subgroup in the 8 mg ramucirumab cohort included some patients who received the combination in first line. All of the patients with gastric/GEJ cancer in the second cohort received the combination in second or third line.

Data analysis included 24 patients from the 8 mg/kg ramucirumab cohort and 17 from the 10 mg/kg cohort. For both cohorts combined, the most common adverse events (AEs) (all grades) were fatigue (32%), decreased appetite (12%), nausea (7%), and abdominal pain, pyrexia, cough, and dyspnea (5% each). Grade ≥3 AEs were infrequent. Treatment-related AEs of particular interest (all grades) included rash (17%), infusion-related reaction (15%), hypertension (12%), endocrine disorders (12%), pruritus (10%), colitis (7%), and diarrhea, pulmonary embolism, epistaxis, and elevated liver enzymes (5% each).

Chau reported that three patients in the 8 mg ramucirumab cohort and 1 in the 10 mg cohort had partial responses for an overall response rate of 10%. The disease control rate was 42% in the 8 mg cohort, 53% in the 10 mg cohort, and 46% overall (19 of 41 patients).

Patients in the 8 mg cohort had a median PFS of 2.10 months, and those in the 10 mg cohort had a median PFS of 2.6 months.

An analysis of the patients who responded to treatment showed that all four had GEJ disease. Two patients had tumors that expressed PD-L1, 1 tested PD-L1 negative, and the fourth responding patient had unknown PD-L1 status. Two of the 4 were former smokers, and 2 had never smoked. The patients had received a variety of prior systemic therapies.

Reference:

Chau I, Bendell J, Calvo E, et al. Interim safety and clinical activity in patients with advanced gastric or gastroesophageal junction adenocarcinoma from a multi-cohort phase 1 study of ramucirumab plus pembrolizumab. Poster presented at: 2017 Gastrointestinal Cancers Symposium; January 19, 2017; San Francisco, CA. Abstract 102.