AB521 for Renal Cell Carcinoma

(ARC-20 Trial)

This trial explores a new treatment called casdatifan (also known as AB521) for individuals with advanced cancers, specifically targeting clear cell renal cell carcinoma (ccRCC), a type of kidney cancer. Researchers aim to assess the safety of casdatifan both alone and in combination with other drugs like cabozantinib or zimberelimab. Those diagnosed with ccRCC or another solid tumor who have exhausted all other treatment options might be suitable candidates for this trial. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

The trial information does not specify if you need to stop taking your current medications. However, you cannot have had certain treatments like a HIF-2α inhibitor or cabozantinib before joining the trial.

Research shows that casdatifan, when used alone for patients with clear cell renal cell carcinoma (ccRCC), is generally well-tolerated. Studies have found that most patients experience only a few side effects. Additionally, casdatifan has shown promising results when combined with cabozantinib, and this combination also has a manageable safety profile, with most patients not experiencing severe side effects.

For those considering the combination of casdatifan and zimberelimab, available data suggests that casdatifan alone has been safe in past studies, and zimberelimab is generally well-tolerated in similar treatments. However, detailed safety information for this specific combination is limited.

Researchers are excited about AB521 for renal cell carcinoma because it introduces casdatifan, a novel treatment that may offer new hope for patients. Unlike standard treatments like sunitinib or pembrolizumab, which primarily target angiogenesis or the immune system, casdatifan works by a potentially unique mechanism that is not yet widespread in current therapies. Additionally, its flexible administration—taken orally and sometimes in combination with other drugs like cabozantinib or zimberelimab infusion—could enhance its effectiveness and patient convenience. This new approach might lead to improved outcomes for patients who have limited options with existing therapies.

Research has shown that casdatifan, which participants in this trial may receive, may help treat kidney cancer. In patients with advanced kidney cancer, casdatifan alone led to a 35% overall response rate, meaning 35% of patients saw their cancer shrink or disappear. On average, these patients went 9.7 months without their cancer worsening. In this trial, some participants will receive casdatifan combined with cabozantinib. Previous studies demonstrated that nearly half of the patients responded positively to this combination. Specifically, 4% of patients had their cancer completely disappear, and 42% saw it shrink. This combination also showed a 46% response rate in patients with clear cell renal cell carcinoma (ccRCC). These results suggest that casdatifan, both on its own and with cabozantinib, could effectively manage ccRCC.³⁶⁷⁸⁹