ASCO-GU 2026 – casdatifan starts to look competitive

This weekend’s ASCO Genitourinary Cancers symposium would have been a non-event for Arcus’s casdatifan – had the company not slipped into it the first disclosure about median progression-free survival. This makes casdatifan look far better than Merck & Co’s rival approved HIF2α inhibitor Welireg on a cross-trial basis, and Arcus stock climbed 7% on Tuesday.

Until now all investors had to go on from casdatifan’s Arc-20 study in relapsed kidney cancer were response rate data, plus the assurance that median PFS hadn’t been reached. Now mPFS has been hit, and amounts to 17.9 months, Arcus revealed in its ASCO-GU announcement. The corresponding number from Welireg’s Litespark-005 trial is just 5.6 months.

The 17.9 months relates specifically to the 100mg daily casdatifan dose on which Arcus zeroed in last year. The dataset still concerns the same 31 patients as at an August 2025 cutoff, but now with an additional five and a half months’ median follow-up.

More responders too

Another positive sign was that the ORR for these same patients had gone up from 35% to 45%. This appears to be down to two previously unconfirmed partial responses now having been confirmed, plus a previous non-responder developing a partial response.

Again the comparison with the admittedly much bigger Litespark-005 study is flattering: there Welireg scored an ORR of only 22%. Arcus’s ASCO-GU presentation formally relates to biomarker data from Arc-20, but the company announced that it had carried out an efficacy analysis at a 30 January cutoff, and this is to be included also. 

Perhaps surprisingly, no fresh safety analysis was done at the same time, Arcus said, adding only that casdatifan’s “safety profile remained consistent with the August 2025 data cutoff”. Safety remains crucial given Welireg’s documented anaemia and hypoxia toxicities, and the fact these had crept up in Arc-20 as that dataset evolved.

Another aspect yet to be determined is whether casdatifan is showing a dose/response relationship – something that would lend support to these early data. Arcus provided a pooled analysis of dosing up to 150mg daily, and this showed mPFS of 12.2 months; that might of course have been pulled down by the lowest dose in this analysis, 50mg daily.

Cross-trial HIF2α inhibitor comparison in relapsed kindey cancer

Source: ASCO-GU & OncologyPipeline.

Casdatifan has become Arcus’s most important pipeline project after the deprioritisation of the company’s anti-TIGIT MAb domvanalimab. Mizuho’s Salim Sayed wrote in a note to clients that mPFS nearly three times higher than Welireg’s was starting to solidify casdatifan as the superior HIF2α inhibitor.

The monotherapy setting is one thing, but Arcus has increasingly been moving towards combining casdatifan with Cabometyx in immunotherapy-relapsed kidney cancer, starting the phase 3 Peak-1 study testing this approach last September. It’s possible that cross-trial superiority on PFS for the monotherapy will translate into similar superiority for the combo, though evidence for this is still early.

A combo cohort in Arc-20 tested a Cabometyx combo and found a 46% ORR, which compared favourably against the 31% that Welireg plus Cabometyx scored in an uncontrolled phase 1 study. Still, for Welireg the much more important combo is with Lenvima, specifically tested in the phase 3 Litespark-011 trial, where it beat Cabometyx on PFS though not on OS.

Full Litespark-011 data are to be presented at an ASCO-GU late-breaking session this weekend. Meanwhile, it remains notable that Arcus’s long-standing partner Gilead has declined to opt in to casdatifan; on Monday Gilead bought out another partner, Arcellx.