In the STELLAR-303 trial, zanzalintinib combined with atezolizumab showed significant improvements in overall survival compared to regorafenib in patients with previously treated metastatic colorectal cancer. The combination achieved a median overall survival of 10.9 months versus 9.4 months with regorafenib, and demonstrated greater efficacy across various subgroups. The regimen was associated with higher rates of adverse events.
Study
|
Randomised, open-label, phase 3 trial [STELLAR-303] |
| Metastatic colorectal cancer that is not MSI-H or dMMR, progressed/refractory to FP, irinotecan, oxaliplatin |
| Zanzalintinib+atezolizumab (n=451) vs regorafenib (n=450)
|
Efficacy
|
ORR: 4% vs 1% |
| mOS: 10.9 mos vs 9.4 mos (zanzalintinib + atezolizumab vs. regorafenib) (HR 0.80 [0.69-0.93]) |
| mOS in non-liver met pts: 15.9 mos vs. 12.7 mos (HR: 0.79 [0.61-1.03]) |
| mPFS: 3.7 mos vs 2.0 mos (HR 0.68 [0.59-0.79])
|
Safety
|
Grade >=3 AEs: hypertension (15% vs 9%), proteinuria (6% vs 2%), fatigue (6% vs 2%), diarrhoea (6% vs 2%) |
| Serious AEs: 26% vs 10% |
| Treatment-related deaths: 1% vs <1%
|
Lancet Published online October 20, 2025
Hecht JR, Park YS, Tabernero J New Drug: Zanzalintinib for Metastatic Colorectal Cancer
http://doi.org/10.1016/S0140-6736(25)02025-2
Reviewed by Ulas D. Bayraktar, MD on Oct 26, 2025
