Casdatifan shows activity across treatment settings in advanced ccRCC

Casdatifan, an investigational hypoxia-inducible factor 2-alpha (HIF-2α) inhibitor, demonstrated antitumor activity across first-line, second-line, and later-line treatment settings for advanced clear cell renal cell carcinoma (ccRCC), according to findings from the phase 1 ARC-20 platform study (NCT05536141) shared by Arcus Biosciences.¹

The findings, based on data collected through September 4, 2026, provide additional evidence supporting further investigation of HIF-2α inhibition in ccRCC.

“Across the RCC treatment continuum, and in every setting in which it has been studied, casdatifan has shown rapid disease control, a meaningful impact on survival, and was tolerable, both alone and in combination with standard-of-care therapies,” said Rana R. McKay, MD, professor of medicine, urology, and radiation medicine and associate director of clinical sciences at UC San Diego Moores Cancer Center, in the news release on the results.¹ “These are the attributes that matter most to physicians and patients.”

ARC-20 findings across treatment cohorts

First-line setting

In the first-line setting, 30 patients who received casdatifan plus zimberelimab had a median follow-up of 11.5 months. The confirmed objective response rate (cORR) was 50%, and landmark progression-free survival at 6 and 12 months were 86% and 69%, respectively. Primary progression, defined as progression at or before the first scan, occurred in 6.7% of patients (2 of 30).

The company compared these results with historical outcomes reported for pembrolizumab (Keytruda) monotherapy and nivolumab (Opdivo) plus ipilimumab (Yervoy). In the respective benchmark studies, pembrolizumab monotherapy was associated with a cORR of 36%, primary progression rate of 30%, and landmark PFS rates of 61% at 6 months and 38% at 12 months. Nivolumab plus ipilimumab was associated with a cORR of 39%, primary progression rate of 20%, and landmark PFS rates of 65% and 50% at 6 and 12 months, respectively.

A separate first-line cohort evaluated casdatifan plus ipilimumab and zimberelimab. Among 24 patients with at least 1 scan and a median of 3 months follow-up, 1 patient (4%) experienced primary progression. The company reported no unexpected safety signals in this cohort of 31 patients. Arcus also noted that safety data from this cohort are expected to support the registrational PEAK-20 trial, which will evaluate casdatifan plus ipilimumab plus nivolumab. The trial is expected to launch in Q4 of 2026.

Second-line setting

In the second-line setting, 43 patients treated with casdatifan plus cabozantinib (Cabometyx) had a median PFS of 14.5 months after a median follow-up of 21.3 months. The 18-month landmark overall survival (OS) rate was 77%, the cORR was 44%, and primary progression occurred in 5% of patients. According to the company, efficacy was similar among patients who had received a prior tyrosine kinase inhibitor (TKI) and those who had not.

The ongoing phase 3 PEAK-1 trial is designed to compare casdatifan plus cabozantinib with cabozantinib plus placebo in patients with advanced ccRCC whose disease has progressed on or after prior anti–PD-1 or anti–PD-L1 therapy.

Later-line setting

In the later-line setting, pooled data from 121 patients treated with casdatifan monotherapy showed a median OS of 35 months, a median PFS of 13 months, and a cORR of 36% after a median follow-up of 28 months. More than half of these patients (52%) had received at least 3 prior lines of treatment. According to Arcus, PFS findings were similar among patients who had received 1, 2, or 3 prior TKI-inclusive treatments.

The monotherapy analysis combined 4 dose cohorts: 50 mg once daily, 50 mg twice daily, 100 mg once daily, and 150 mg once daily. The company reported no unexpected safety signals and characterized adverse events as manageable across all doses. Arcus noted plans to initiate a registrational trial evaluating casdatifan plus tivozanib vs tivozanib alone.

Next steps

The next stage of development will test whether the activity observed in ARC-20 translates into clinically meaningful benefits in controlled trials. PEAK-1 is evaluating casdatifan plus cabozantinib against cabozantinib alone in immunotherapy-experienced patients with advanced ccRCC. The company has also outlined plans for PEAK-20, a first-line registrational study of casdatifan with ipilimumab and nivolumab, and a study of casdatifan plus tivozanib in a later-line setting.

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REFERENCE
1. Arcus presents new data from ARC-20 that demonstrate the upportunity for casdatifan to become a foundational treatment across all lines of therapy in kidney cancer. News release. Arcus Biosciences. October 20, 2026. Accessed October 20, 2026. https://investors.arcusbio.com/investors-and-media/press-releases/press-release-details/2026/Arcus-Presents-New-Data-from-ARC-20-that-Demonstrate-the-Opportunity-for-Casdatifan-to-Become-a-Foundational-Treatment-Across-All-Lines-of-Therapy-in-Kidney-Cancer/default.aspx