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Volrustomig's pivotal dish has a casdatifan side helping

One of AstraZeneca's key future hopes in oncology, the anti-PD-1 x CTLA-4 MAb volrustomig, is about to start its fifth potentially pivotal trial. The Evolve-RCC02 study, just revealed on clinicaltrials.gov, concerns first-line renal cell cancer, and adds to volrustomig's ongoing phase 3s in first-line lung and mesothelioma, and head and neck and cervical cancer maintenance trials. An intriguing aspect of Evolve-RCC02 is that in addition to volrustomig monotherapy it includes a combination with Arcus's HIF2α inhibitor casdatifan, which Arcus has increasingly been playing up as enthusiasm wanes for its Gilead-partnered lead, the anti-TIGIT MAb domvanalimab. However, Evolve-RCC02 isn't immediately pivotal; formally it's a phase 1b/3 study, which will first aim to find an optimal dose, based on adverse events, that will then be taken into its controlled phase 3 part, where it will be compared against Opdivo plus Yervoy. The world's most advanced anti-PD-1 x CTLA-4 bispecific is Akeso's cadonilimab, which on Wednesday received its third Chinese approval, in first-line cervical cancer as part of a combo with Avastin and/or chemo, based on the Compassion-16 study. Outside China, however, there have been setbacks, with Xencor discontinuing vudalimab in February. MacroGenics's lorigerlimab has been delayed, but remains that company's lead project.

 

Pivotal trials of volrustomig

StudyTumourDesignControlPrimary endpoint
Evolve-RCC021st-line renal cancer+/- casdatifanOpdivo + YervoyPFS & OS
Evolve-HNSCCMaintenance in head & neck cancerMonoRx, patients in response to chemoradiationObservationPFS
Evolve-Meso1st-line mesotheliomaChemo comboChemo, or Opdivo + YervoyOS
Evolve-CervicalMaintenance in cervical cancerMonoRx, patients in response to chemoradiationPlaceboPFS
Evolve-Lung021st-line PD-L1<50% NSCLCChemo comboKeytruda + chemoPFS & OS

Source: OncologyPipeline.

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