Denosumab and Pembrolizumab in clear cell renal carcinoma: a phase II trial (ANZUP1601)

Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer. Mainstay treatment for advanced ccRCC involves using tablets that block the blood supply to the cancer. This treatment usually fails, so further therapy options are required. Recently, immunomodulatory drugs, such as pembrolizumab, have been shown to be effective in advanced ccRCC, as well as in other cancers. They work by targeting the PD-1 receptor on immune T cells, which then mobilises a person’s immune system to kill cancer cells.

The ANZUP-CTC Phase II KEYPAD trial is a second-line study in advanced ccRCC designed to test the activity and safety of pembrolizumab in combination with denosumab, a drug that has traditionally been used for bone support. Denosumab is an antibody that works by blocking a signalling molecule called RANK ligand (RANKL). More recently, studies have found that blocking RANKL also stimulates the immune system and potentially has a synergistic effect with other immunomodulatory drugs to fight cancer.

This trial will recruit 70 patients over 16 Australian sites, and all participants on the study will receive both pembrolizumab and denosumab. The study aims to determine whether giving both drugs together will improve tumour response and survival in advanced kidney cancer. Both pembrolizumab and denosumab have very favourable individual safety profiles, and the study will also assess their tolerability as a combination.

See ANZCTR for full trial details >


Trial Summary:

Single-arm, multicentre, phase 2 trial to determine the activity and safety of pembrolizumab and denosumab in advanced clear cell renal cell carcinoma (ccRCC).

Supported By:



Adults with unresectable or metastatic ccRCC progressing after treatment with a VEGFR TKI.

Registration ID:




Australian Lead Group:




Activation Date:



Dr Craig Gedye