In previous clinical trials of patients with advanced renal cell carcinoma (aRCC), including CheckMate 214, patients with brain metastases have been excluded. However, according to Hamid Emamekhoo, MD, and colleagues, antitumor activity has been observed in patients with melanoma treated with nivolumab (1 mg/kg) plus ipilimumab 3 mg/kg) with brain metastases; antitumor activity has also been observed in patients with non-small cell lung cancer treated with nivolumab (240 mg) plus ipilimumab (1 mg/kg).
During a poster session at the ASCO 2019 Annual Meeting, the researchers presented safety and efficacy results of the CheckMate 920 trial, an ongoing, phase 3b/4 clinical trial of nivolumab plus ipilimumab in patients with aRCC not on corticosteroids or receiving radiation with Karnofsky performance status ≥70%. The poster was titled Safety and Efficacy of Nivolumab plus Ipilimumab (NIVO+IPI) in Patients with Advanced Renal Cell Carcinoma (aRCC) with Brain Metastases: Interim analysis of CheckMate 920.
Eligible patients were assigned to treatment with nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses, followed by nivolumab 480 mg every 4 weeks. Treatment continued until disease progression, unacceptable toxicity, or for a maximum of 2 years.
The primary end point of interest was the incidence of high-grade immune-mediated adverse events. Secondary end points included progression-free survival and objective response rate by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) per investigator. Additional safety analyses and overall survival were exploratory end points.
A total of 28 patients were enrolled in the brain metastases cohort. During a minimum follow-up of 6.47 months, there were six cases of grade 3 to 4 immune-mediated adverse events within 100 days of the last dose. Grade 3 to 4 immune-mediated adverse events observed in ≥1 patents were diarrhea, colitis, diabetic ketoacidosis, immune-mediated hepatitis, hypophysitis, and rash of any type (n=1 each). There were no treatment-related immune-mediated adverse events grade 5 reported.
Median progression-free survival in all treated subjects was 9.0 months. Median overall survival has not been reached.
“In patients with aRCC and brain metastases who are often excluded from clinical trials, nivolumab plus ipilimumab treatment showed a safety profile consistent with previous reports of this dosing regimen, with encouraging antitumor activity,” the researchers said.
Source: Emamekhoo H, Olsen M, Carthon BC, et al. Safety and efficacy of nivolumab plus ipilimumab (NIVO+IPI) in patients with advanced renal cell carcinoma (aRCC) with brain metastases: Interim analysis of CheckMate 920. Abstract of a poster presented at the American Society of Clinical Oncology 2019 Annual Meeting, June 3, 2019, Chicago, Illinois.