
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
Study | Tumour | Design | Control | Primary endpoint |
---|---|---|---|---|
Evolve-RCC02 | 1st-line renal cancer | +/- casdatifan | Opdivo + Yervoy | PFS & OS |
Evolve-HNSCC | Maintenance in head & neck cancer | MonoRx, patients in response to chemoradiation | Observation | PFS |
Evolve-Meso | 1st-line mesothelioma | Chemo combo | Chemo, or Opdivo + Yervoy | OS |
Evolve-Cervical | Maintenance in cervical cancer | MonoRx, patients in response to chemoradiation | Placebo | PFS |
Evolve-Lung02 | 1st-line PD-L1<50% NSCLC | Chemo combo | Keytruda + chemo | PFS & OS |
Source: OncologyPipeline.
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