Denosumab plus pembrolizumab in advanced clear cell renal cell carcinoma

Preliminary studies have demonstrated that denosumab, an inhibitor of receptor activator of NF-κB ligand (RANKL), may potentiate the effects of the PD-1 inhibitor pembrolizumab. This potential was further studied in the KEYPAD trial in patients with unresectable or metastatic clear cell renal cell carcinoma (ccRCC).

Dr Craig Gedye (Calvary Mater Newcastle, Australia) discussed the KEYPAD trial (NCT03280667) at ASCO GU 2021 [1]. While some benefit is derived from treatment with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors, the prognosis for patients with unresectable or metastatic ccRCC remains poor, as the disease inevitably progresses. Cytokine immunotherapy, although highly toxic, has met with some success.

KEYPAD is a single-arm, multicentre, phase 2 trial aiming to investigate the activity and safety of combining denosumab with pembrolizumab in unresectable or metastatic ccRCC. The study will recruit 70 adults who will receive 200 mg pembrolizumab intravenously every 3 weeks (Q3W) combined with 120 mg denosumab subcutaneous on days 1, 8 and 22 and then Q3W until disease progression, toxicity, or participant withdrawal, up to a maximum of 2 years.

The primary completion date is scheduled for December 2022. The primary outcome measure will be the objective tumour response rate, as measured by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. Secondary outcome measures to be tracked are progression-free survival, disease control rate, time to objective tumour response, time to first skeletal-related event, frequency and severity of adverse events, and frequency of treatment delays and discontinuation due to toxicity.

Dr Gedye concluded that favourable outcomes may lead to a new standard of care and would offer new hope for those afflicted with unresectable or metastatic ccRCC.

1. Gedye C. Denosumab and pembrolizumab in clear cell renal carcinoma (KEYPAD): A Phase 2 trial (ANZUP1601). Abstract TPS367, ASCO Genitourinary Cancers Symposium, 11–13 February 2021.

 

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Posted on 24 March 202127 March 2024