Checkpoint Inhibitor May Be New Tool Against Metastatic Renal Cell Carcinoma

Checkpoint Inhibitor May Be New Tool Against Metastatic Renal Cell Carcinoma

November 19, 2015

Pembrolizumab (Keytruda), a PD-1 or “checkpoint” inhibitor, is showing promise against metastatic renal cell carcinoma (RCC), and now is being tested in a phase II trial to determine what effects it may have when combined with bevacizumab (Avastin) in patients with metastatic kidney cancer.

Pembrolizumab (Keytruda), a PD-1 or “checkpoint” inhibitor, is showing promise against metastatic renal cell carcinoma (RCC), and now is being tested in a phase II trial to determine what effects it may have when combined with bevacizumab (Avastin) in patients with metastatic kidney cancer.

The study, known as BTCRC-GU14-003, will examine several issues. One cohort will consist of a small group of patients who will receive pembrolizumab 200 mg and bevacizumab 5 mg on day 1 of the 21-day cycle. Both agents are administered 15-30 minutes apart in separate intravenous infusions.  A second cohort will include patients who will receive pembrolizumab 200 mg and bevacizumab 10 mg on day 1 of the 21-day cycle.

“For patients with advanced stages of kidney cancer, effective treatment options are limited. By exploring therapies that harness one’s own immune system, there is an opportunity to address an unmet need in this patient population,” said study investigator Eric Singer, MD, MA, FACS, who is a urologic oncologist at Rutgers Cancer Institute and assistant professor of surgery at Rutgers Robert Wood Johnson Medical School in New Brunswick, New Jersey, in a press release.

Pembrolizumab is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. It blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, activating T lymphocytes which may affect both tumor cells and healthy cells.

The US Food and Drug Administration (FDA) have pembrolizumab monotherapy at a dose of 2 mg/kg every 3 weeks for the treatment of patients with metastatic non-small cell lung cancer (NSCLC). It is only approved for those patients with NSCLC whose tumors express PD-L1 as determined by an FDA-approved test and who have disease progression on or after platinum-containing chemotherapy.  Pembrolizumab is also approved for melanoma that cannot be removed by surgery or that has metastasized. It is used in patients whose disease progressed after being treated with ipilimumab (Yervoy) and if their cancer consists of a certain BRAF gene mutation.

The most common side effects associated with this agent are anemia, fatigue, hyperglycemia, hyponatremia, hypoalbuminemia, itching, cough, and nausea.  

This current investigation is being run in conjunction with the Big Ten Research Consortium (BTCRC). The Phase Ib and Phase II Studies of MK-3475 in Combination + for Renal Cell Carcinoma is currently recruiting patients and will include patients 18 and older with histologically assessed metastatic clear cell RCC (defined as more than 50% clear cell component).