Merck keeps its kinase inhibitor options open

Exelixis wants zanzalintinib to become the kinase inhibitor of choice for combinations, and on Monday it got an endorsement from Merck, which will now test the asset alongside its HIF2α inhibitor Welireg in renal cancer. However, the collaboration raises questions about the big pharma’s other renal efforts with Welireg – particularly with Lenvima. The primary completion data of the Litespark-011 trial of Welireg plus Lenvima in second-line RCC was recently changed, from December 2024 to February 2026. Such a delay is rarely a good sign, and the deal will only add to speculation that Litespark-011 is doomed. Lenvima, a multi-kinase inhibitor, is linked with significant side effects; perhaps Merck is looking for something less toxic, although zanzalintinib is also broad acting, hitting MET, AXL, MER and VEGFR. There are few details about the collaboration, except that the companies will co-fund a phase 1/2 trial, with Merck paying for one phase 3 and Exelixis another; all three studies will be sponsored by Merck. Merck will also supply Keytruda for an ongoing Exelixis-sponsored trial in first-line head and neck cancer, Stellar-305. Exelixis is already testing zanzalintinib plus Opdivo in first-line non-clear cell renal cancer, in Stellar-304.

Welireg’s phase 3 renal cancer trials

Source: OncologyPipeline, clinicaltrials.gov.