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Some backing for Arcus's HIF2α bet

Arcus has bet on its HIF2α inhibitor casdatifan as part of a combination with Cabometyx rather than as monotherapy, but the latter setting is still key to gauging the molecule's overall potential. Updated findings from the phase 1 Arc-20 study were presented on Monday, zeroing in on a 100mg daily casdatifan dose, and showing an uptick in response rates – and toxicities – versus those presented at ASCO-GU in February. In essence, with another 12 months of data, Arcus has seen responses in all four additional late-line kidney cancer patients dosed, with two responses confirmed. The focus is increasingly on progression-free survival, given that small molecules often yield impressive-sounding responses that fail to be sustained, and here Evercore ISI's Jonathan Miller was expecting a result "at least in the mid to high teens; 17-18 months is good". Now, at 12.4 months' median follow-up, casdatifan 100mg still hasn't reached median PFS, which is surely a positive sign. Both this and ORR are better than Merck & Co's Welireg on a cross-trial basis, and PFS and safety data still appear to bode well for Arcus's efforts to combine the 100mg dose with Cabometyx in the Peak-1 phase 3 trial; Arcus stock opened up 8% on Monday.

 

Cross-trial comparison in HIF2α inhibition

 Casdatifan 100mg dailyWelireg 120mg
TrialArc-20Litespark-005
Cutoff30 Aug 202415 Aug 20251 Nov 2022
Efficacy-evaluable patients2731373
Confirmed ORR33%35%*22%
mPFSNRNR5.6 mth
Median follow-up5.0mth12.4mthNA
Serious treatment-emergent AEs24%31%38%
Gr3+ treatment-related anaemia17%25%33%
Gr3+ treatment-related hypoxia10%9%11%

Note: *2 additional responders pending confirmation. Source: ASCO-GU, company statement & prescribing info.

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