{"entity":{"id":"codebreak-300","kind":"trial","name":"CodeBreaK 300","aka":[],"tldr":"CodeBreaK 300 showed that a KRAS drug needs an EGFR antibody partner to work in colorectal cancer.","summary":"CodeBreaK 300, trial NCT05198934 sponsored by Amgen and published in the New England Journal of Medicine in 2023, showed that a KRAS G12C inhibitor needs an EGFR antibody partner to work in colorectal cancer. It randomised 160 patients with previously treated KRAS G12C colorectal cancer to sotorasib at two doses with panitumumab or standard trifluridine-tipiracil or regorafenib, met its primary progression-free survival endpoint for the 960 mg dose with responses in about a quarter against none, and led to approval in January 2025. OnCo links it to colorectal cancer, KRAS and EGFR as targets, sotorasib, panitumumab, the pairing of a KRAS G12C inhibitor with an anti-EGFR antibody and the CodeBreaK 200 and 300 papers. Whether the combination can move into first-line treatment is the open question.","status":"positive","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT05198934","url":"https://clinicaltrials.gov/study/NCT05198934"}],"tags":[],"related":[],"cancers":["colorectal","kras-g12c-colorectal"],"sections":[],"technologies":["kras-inhibitors"],"targets":["kras","egfr"],"drugs":["sotorasib"],"companies":["amgen"],"institutions":[],"pathways":[],"terms":[],"trials":["nct06252649"],"people":[],"bottlenecks":[],"keyPapers":["paper-codebreak-300-nejm-2023","paper-schirripa-kras-g12c-metastatic-colorectal-clin-colorectal-cancer-2020"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT05198934","phase":"3","setting":"KRAS G12C colorectal cancer, previously treated: sotorasib + panitumumab vs standard of care","sponsor":"Amgen","result":"PFS HR 0.49.","started":"2022-04-19","startedType":"actual","yearReported":2023,"enrolled":160,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival (BICR), sotorasib 960 mg + panitumumab","primary":true,"unit":"months","arms":[{"name":"Sotorasib 960 mg + panitumumab","n":53,"value":5.6},{"name":"Trifluridine-tipiracil or regorafenib","n":54,"value":2.2}],"hr":0.49,"ci":[0.3,0.8],"p":"0.006","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2308795"},{"endpoint":"Objective response rate","unit":"%","arms":[{"name":"Sotorasib 960 mg + panitumumab","value":26.4},{"name":"Trifluridine-tipiracil or regorafenib","value":0}],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2308795"}],"replication":"Consistent with KRYSTAL-1 (adagrasib + cetuximab, ORR 34%), so the KRAS G12C + anti-EGFR combination is supported by two independent programmes."},"route":"/trials/codebreak-300/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"kras-g12c-colorectal","kind":"cancer","name":"KRAS G12C-mutant colorectal cancer","route":"/cancers/kras-g12c-colorectal/"}],"technology":[{"id":"kras-inhibitors","kind":"technology","name":"KRAS & RAS inhibitors","route":"/technologies/kras-inhibitors/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"}],"drug":[{"id":"panitumumab","kind":"drug","name":"Panitumumab","route":"/drugs/panitumumab/"},{"id":"sotorasib","kind":"drug","name":"Sotorasib","route":"/drugs/sotorasib/"}],"company":[{"id":"amgen","kind":"company","name":"Amgen","route":"/companies/amgen/"}],"trial":[{"id":"nct04793958","kind":"trial","name":"Phase 3 Study of MRTX849 With Cetuximab vs Chemotherapy in Patients With Advanced Colorectal Cancer With KRAS G12C Mutation (KRYSTAL-10)","route":"/trials/nct04793958/"},{"id":"nct06252649","kind":"trial","name":"Study of Sotorasib, Panitumumab and FOLFIRI Versus FOLFIRI With or Without Bevacizumab-awwb in Treatment-naïve Participants With Metastatic Colorectal","route":"/trials/nct06252649/"}],"paper":[{"id":"paper-codebreak-200-lancet-2023","kind":"paper","name":"CodeBreaK 200: sotorasib versus docetaxel in KRAS G12C-mutated lung cancer, a modest win for the first KRAS drug","route":"/key-papers/paper-codebreak-200-lancet-2023/"},{"id":"paper-codebreak-300-nejm-2023","kind":"paper","name":"CodeBreaK 300: sotorasib plus panitumumab in chemotherapy-refractory KRAS G12C colorectal cancer","route":"/key-papers/paper-codebreak-300-nejm-2023/"},{"id":"paper-schirripa-kras-g12c-metastatic-colorectal-clin-colorectal-cancer-2020","kind":"paper","name":"KRAS G12C metastatic colorectal cancer: specific features of a new emerging target population","route":"/key-papers/paper-schirripa-kras-g12c-metastatic-colorectal-clin-colorectal-cancer-2020/"}],"idea":[{"id":"idea-bio1-pan-ras-covalent-g12d","kind":"idea","name":"Covalent chemistry for the RAS mutations that still have no drug","route":"/ideas/idea-bio1-pan-ras-covalent-g12d/"},{"id":"idea-immunotherapy-mss-crc","kind":"idea","name":"Making microsatellite-stable colorectal cancer immunotherapy-responsive","route":"/ideas/idea-immunotherapy-mss-crc/"},{"id":"idea-shared-kras-vaccine-adjuvant","kind":"idea","name":"Off-the-shelf KRAS vaccines after pancreatic cancer surgery","route":"/ideas/idea-shared-kras-vaccine-adjuvant/"}],"roadmap":[{"id":"colorectal-roadmap","kind":"roadmap","name":"Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation","route":"/roadmaps/colorectal-roadmap/"},{"id":"targeted-therapy-roadmap","kind":"roadmap","name":"Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall","route":"/roadmaps/targeted-therapy-roadmap/"}],"pairing":[{"id":"kras-plus-egfr-crc","kind":"pairing","name":"KRAS G12C inhibitor + anti-EGFR antibody (colorectal)","route":"/pairings/kras-plus-egfr-crc/"}],"biomarker":[{"id":"ras-wild-type","kind":"biomarker","name":"RAS wild-type (extended KRAS and NRAS testing)","route":"/biomarkers/ras-wild-type/"}]}}