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 this dose 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 volrustomigStudyTumourDesignControlPrimary endpointEvolve-RCC021st-line renal cancer+/- casdatifanOpdivo + YervoyPFS & OSEvolve-HNSCCMaintenance in head & neck cancerMonoRx, patients in response to chemoradiationObservationPFSEvolve-Meso1st-line mesotheliomaChemo comboChemo, or Opdivo + YervoyOSEvolve-CervicalMaintenance in cervical cancerMonoRx, patients in response to chemoradiationPlaceboPFSEvolve-Lung021st-line PD-L1<50% NSCLCChemo comboKeytruda + chemoPFS & OSSource: OncologyPipeline.