Merck and Exelixis reveal their combo study
Merck & Co has finally pulled back the curtain on its long-awaited phase 3 trial pairing Welireg against Exelixis’s Cabometyx follow-on zanzalintinib. The study, Litespark-033, has now landed on clinicaltrials.gov, and is set to kick off before the end of the year. This is the first of two phase 3 trials in renal cancer that the partners promised when they signed a deal last year, with silence still surrounding the second. Litespark-033 will evaluate the Welireg/zanzalintinib combo against Cabometyx in the post adjuvant PD-(L)1 setting, mirroring the indication explored in the phase 1/2 trial that started earlier this year. Beyond efficacy, Litespark-033 will be a crucial test of whether zanzalintinib’s safety profile truly offers an advantage over Cabometyx, a question raised during ESMO after the company reported five treatment-related deaths in the active cohort of the Stellar-303 trial in relapsed colorectal cancer. Meanwhile, Merck enters the new trial with momentum; after a string of Lenvima disappointments the company finally notched up a win last month when the Litespark-011 study of Welireg plus Lenvima in a post-IO setting hit one of its co-primary endpoints of PFS; however, there was only a trend towards a benefit on the other co-primary, overall survival.
Welireg phase 3 studies in renal cell carcinoma
| Trial name | Setting | Regimen | Note |
|---|---|---|---|
| Litespark-005 | 3rd-line (post-PD-(L)1 & VEGF-TKI) | Monotherapy | Approved Dec 2023 |
| Litespark-011 | 2nd-line-plus (post PD-(L)1) | Welireg + Lenvima, vs Cabometyx | Primary endpoint of PFS met in Oct 2025; positive OS trend at interim analysis |
| Litespark-022 | Adjuvant | Welireg + Keytruda, vs Keytruda | Primary endpoint met in Oct 2025 |
| Litespark-012 | 1st-line | Welireg + Lenvima + Keytruda, vs Lenvima + Keytruda | Primary completion Oct 2026 |
| Litespark-033 | Post adjuvant PD-(L)1 | Welireg + zanzalintinib, vs Cabometyx | Primary completion Feb 2032 |
Source: OncologyPipeline.
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