Results from the phase 2 KEYPAD trial suggest that combining pembrolizumab with denosumab may benefit patients with advanced clear-cell renal cell carcinoma (ccRCC) whose cancer progressed after previous VEGFR-targeted therapy. The Australian single-arm study enrolled 59 patients with unresectable or metastatic disease.
The combination achieved an objective response rate of 31%, with all responses being partial. Although this did not reach the trial’s target of 40%, the results were similar to those seen with other second-line immunotherapy treatments. Median progression-free survival was 7.5 months, and responses lasted a median of 17 months. Patients with bone metastases also benefited, with a 29% response rate.
Treatment-related side effects were common, with 98% of patients experiencing at least one adverse event and 64% having severe side effects. Immune-related adverse events occurred in 32% of patients, including pneumonitis, myocarditis, and colitis. One treatment-related death from myositis was reported. Serious bone-related side effects from denosumab were uncommon. Researchers are continuing to study which patients are most likely to benefit from adding denosumab to pembrolizumab.