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STELLAR-303

A Randomized Open-Label Phase 3 Study of XL092 + Atezolizumab vs Regorafenib in Subjects With Metastatic Colorectal Cancer

Phase 3N = 901NCT05425940

Population
Previously treated metastatic colorectal cancer without MSI-H or dMMR tumours
Design
Global, randomised, open-label phase 3 trial at 121 centres in 16 countries: patients aged 18 years and older with metastatic colorectal adenocarcinoma who had previously received standard-of-care therapy and did not have MSI-H or dMMR tumours were randomised (1:1, blocks of four; stratified by geographical region, RAS status and presence of liver metastases) to oral zanzalintinib 100 mg daily plus intravenous atezolizumab 1200 mg every 3 weeks, or oral regorafenib 160 mg daily on days 1 to 21 of each 28-day cycle. Dual primary endpoints were overall survival in the intention-to-treat population and in the subset of patients without liver metastases. The report is a planned overall survival analysis (data cutoff 30 April 2025); the trial continues to the final overall survival analysis in the subset without liver metastases. 901 patients were randomised (451 and 450).
Primary endpoint
OS
Arms
  • Regorafenib (control, n = 450): Oral regorafenib 160 mg daily on days 1 to 21 of each 28-day cycle
  • Zanzalintinib plus atezolizumab (experimental, n = 451): Oral zanzalintinib 100 mg daily plus intravenous atezolizumab 1200 mg every 3 weeks
People
Hecht JR
OSHR 0.80 (95% CI 0.69–0.93)Δ median OS+1.5 monthsOSHR 0.79 (95% CI 0.61–1.03)Δ median OS+3.2 months
Show the numbers
Results reported for STELLAR-303
EndpointAnalysisZanzalintinib plus atezolizumabRegorafenibEffect
OSprimarymedian follow-up 18 monthsHecht 2025median 10.9 months (9.9–12.1)median 9.4 months (8.5–10.2)HR 0.80 (95% CI 0.69–0.93)P=0.0045Dual primary endpoint; stratified hazard ratio from a planned overall survival analysis. The abstract gives the interquartile range of follow-up as 14.6-21.5 months.
OSPatients without liver metastases (interim analysis of the second dual primary endpoint)interimHecht 2025median 15.9 months (13.5–17.6)median 12.7 months (10.9–15.5)HR 0.79 (95% CI 0.61–1.03)P=0.087Interim analysis; the trial continues to the final analysis of overall survival in this subset.
Results reported for STELLAR-303
EndpointAnalysisZanzalintinib plus atezolizumabRegorafenibEffect
OSprimarymedian follow-up 18 monthsHecht 2025median 10.9 months (9.9–12.1)median 9.4 months (8.5–10.2)HR 0.80 (95% CI 0.69–0.93)P=0.0045Dual primary endpoint; stratified hazard ratio from a planned overall survival analysis. The abstract gives the interquartile range of follow-up as 14.6-21.5 months.
OSPatients without liver metastases (interim analysis of the second dual primary endpoint)interimHecht 2025median 15.9 months (13.5–17.6)median 12.7 months (10.9–15.5)HR 0.79 (95% CI 0.61–1.03)P=0.087Interim analysis; the trial continues to the final analysis of overall survival in this subset.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS0.80.69–0.93
OS0.790.61–1.03
Illustrative — modelled from reported values, not trial data. OS, primary.
0%25%50%75%100%0510152025Months (modelled)
  • Zanzalintinib plus atezolizumab (experimental)
  • Regorafenib (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsZanzalintinib plus atezolizumabRegorafenib
0100.0%100.0%
764.1%59.7%
1441.1%35.6%
2028.0%22.9%
2718.0%13.7%
Illustrative — modelled from reported values, not trial data. OS, interim.
0%25%50%75%100%0102030Months (modelled)
  • Zanzalintinib plus atezolizumab (experimental)
  • Regorafenib (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsZanzalintinib plus atezolizumabRegorafenib
0100.0%100.0%
1064.7%57.9%
2041.8%33.6%
3027.0%19.4%
4017.5%11.3%
Primary publication: Hecht JR, Park YS, Tabernero J, Lee MA, Lee S, Virgili AC, et al. Zanzalintinib plus atezolizumab versus regorafenib in refractory colorectal cancer (STELLAR-303): a randomised, open-label, phase 3 trial. Lancet. 2025;406(10517):2360-2370. PubMedDOI

Appears in

Sources

  1. Hecht JR, Park YS, Tabernero J, Lee MA, Lee S, Virgili AC, et al. Zanzalintinib plus atezolizumab versus regorafenib in refractory colorectal cancer (STELLAR-303): a randomised, open-label, phase 3 trial. Lancet. 2025;406(10517):2360-2370.

    PubMedDOI