Pietrantonio, FilippoFilippoPietrantonioSalvatore, LisaLisaSalvatoreEsaki, TaitoTaitoEsakiModest, Dominik PaulDominik PaulModestLopez-Bravo, David PaezDavid PaezLopez-BravoTaieb, JulienJulienTaiebKaramouzis, Michalis VMichalis VKaramouzisRuiz-Garcia, ErikaErikaRuiz-GarciaKim, Tae WonTae WonKimKuboki, YasutoshiYasutoshiKubokiMeriggi, FaustoFaustoMeriggiCunningham, DavidDavidCunninghamKUN-HUEI YEHChan, EmilyEmilyChanChao, JosephJosephChaoTran, QuiQuiTranCremolini, ChiaraChiaraCremoliniFakih, MarwanMarwanFakih2026-01-192026-01-192025-07https://scholars.lib.ntu.edu.tw/handle/123456789/735477In the phase III CodeBreaK 300 study, sotorasib 960 mg-panitumumab significantly prolonged progression-free survival (PFS) versus investigator's choice (trifluridine/tipiracil or regorafenib) in patients with G12C-mutated chemorefractory metastatic colorectal cancer (mCRC). One hundred sixty patients were randomly assigned 1:1:1 to receive sotorasib 960 mg-panitumumab (n = 53), sotorasib 240 mg-panitumumab (n = 53), or investigator's choice (n = 54; crossover permitted after primary analysis). Overall survival (OS) analysis, a key secondary end point, although not adequately powered, was prespecified at 50% maturity (after approximately 80 deaths). In this study, we report the OS, updated overall response rates (ORRs), and data for safety. After a median follow-up of 13.6 months, 24, 28, and 30 deaths occurred in the sotorasib 960 mg-panitumumab, sotorasib 240 mg-panitumumab, and investigator's choice arms, respectively; updated objective response rates (ORRs; 95% CI) were 30.2% (95% CI, 18.3 to 44.3), 7.5% (95% CI, 2.1 to 18.2), and 1.9% (95% CI, 0.0 to 9.9), respectively. Compared with investigator's choice, the hazard ratios (HRs [95% CI]) for OS were 0.70 (95% CI, 0.41 to 1.18; two-sided = .20) with sotorasib 960 mg-panitumumab and 0.83 (95% CI, 0.49 to 1.39; two-sided = .50) with sotorasib 240 mg-panitumumab. No new safety signals were observed. Although not statistically significant, the observed OS HR and ORR along with prior PFS and safety findings support sotorasib 960 mg-panitumumab as a standard of care in patients with chemorefractory G12C mCRC.en[SDGs]SDG3journal article10.1200/JCO-24-0202640215429