Not the zanza trial some were looking for

A study in post-immunotherapy renal cancer featuring Merck & Co's HIF2α inhibitor Welireg combined with Exelixis's zanzalintinib has materialised – but it's not the trial some were looking for. Zanzalintinib has been positioned as a key follow-on to Exelixis's ageing workhorse Cabometyx, and there had been hopes that it was about to be tested with Welireg in a phase 3 renal cancer trial. However, the new study, as disclosed in a clinicaltrials.gov listing, is actually a phase 1/2 test with safety lead-in and efficacy phases, but "no hypothesis testing". Formally this is substudy 3C of the Keymaker-03 trial, whose 3A (first-line) and 3B (second-line) Welireg/Keytruda combo cohorts have separate clinicaltrials.gov listings. One intriguing feature of substudy 3C is that it mandates prior progression on anti-PD-(L)1 therapy in the adjuvant setting. That's one consideration for a future comparison against Arcus's rival HIF2α inhibitor casdatifan, whose recently disclosed phase 3 Peak-1 trial tests a Cabometyx combo but enrols patients who progressed on anti-PD-(L)1 drugs in the metastatic setting. Either way, zanzalintinib is moving slowly; any benefit in substudy 3C will need replicating in a formal phase 3 trial, and a Welireg/Lenvima combo seems the primary focus for Merck here. 

HIF2α inhibitors in post-IO renal cancer

Note: *after progressing on adjuvant PD-(L)1 therapy; remaining trials mandate progression in the metastatic setting. Source: OncologyPipeline.