Welireg fails to Lite up

After a couple of recent wins with its HIF-2α inhibitor Welireg, Merck & Co was brought back down to earth on Tuesday with the failure of the phase 3 Litespark-012 trial. The study evaluated Welireg plus Merck and Eisai's Lenvima plus Keytruda, versus Lenvima plus Keytruda alone, in first-line renal cell carcinoma. At an interim analysis it didn’t meet its co-primary endpoints of progression-free and overall survival, the companies said, although full data aren’t yet available. The trial also failed to show a benefit with Lenvima plus MK-1308A, a coformulation of Keytruda and the anti-CTLA-4 MAb quavonlimab. The result might come as a surprise after the success of the adjuvant Litespark-022 trial; however, that focused on a Welireg/Keytruda combo. Merck is awaiting an FDA decision on this use, as well as in post-PD-(L)1 renal cancer, where the Litespark-011 study of Welireg plus Lenvima also recently prevailed. Welireg is currently US approved for third-line disease, following a PD-(L)1 inhibitor and VEGF-TKI. Of late, Merck appears to have been moving away from Lenvima and towards Exelixis’s zanzalintinib, that group’s Cabometyx follow-on. Two phase 3 studies of this combo recently began, including the second-line Litespark-034, against Welireg itself.

Welireg phase 3 studies in renal cell carcinoma

Note: *Also evaluated MK-1308A (Keytruda + quavonlimab coformulation), vs Lenvima + Keytruda. Source: OncologyPipeline.