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(MK-3475) and Chemotherapy in Participants With First-Line Locally Advanced Unresectable/Metastatic Gastroesophageal Adenocarcinoma (MK-3475-06C/KEYMAKER-U06)","nct":"NCT06469944","phase":"1/2","status":"recruiting"},{"id":"nct06445972","name":"Substudy 06D: Combination Therapies in Second Line (2L) Gastroesophageal Adenocarcinoma (MK-3475-06D/Keymaker-U06)","nct":"NCT06445972","phase":"1/2","status":"recruiting"},{"id":"nct06780111","name":"Substudy 06E: Umbrella Study of Combination Therapies in Esophageal Cancer (MK-3475-06E/KEYMAKER-U06)","nct":"NCT06780111","phase":"1/2","status":"recruiting"}],"pathways":["dna-replication-licensing","drug-efflux-pumps"],"companies":["akeso","astrazeneca","avenzo","daiichi-sankyo","gilead","ligachem-biosciences","merck","pathos-ai","kelun-biotech"],"keyPapers":["paper-tropion-breast02-ann-oncol-2026","paper-tropion-breast01-jco-2024","paper-asco-biomarkers-metastatic-breast-cancer-guideline-jco-2022","paper-ascent-nejm-2021","paper-bardia-ascent-trop2-biomarker-ann-oncol-2021"],"hotspots":[],"openQuestions":[{"id":"trop2-patient-selection","question":"Is there any biomarker (IHC, PET, quantitative continuous scoring) that predicts who benefits from a TROP2 ADC?","stage":"translational","actor":"research","source":{"label":"ASCENT, NEJM 2021","url":"https://doi.org/10.1056/NEJMoa2028485"}}],"assays":[],"resistance":[{"class":"egfr-tki","mechanism":"On-target EGFR C797S","category":"on-target"},{"class":"top1-adc","mechanism":"Payload resistance: TOP1 mutation or loss","category":"payload"},{"class":"top1-adc","mechanism":"SLFN11 loss","category":"payload"},{"class":"top1-adc","mechanism":"Efflux pump upregulation (ABCG2, ABCB1)","category":"payload"},{"class":"top1-adc","mechanism":"Antigen loss or downregulation","category":"antigen"},{"class":"top1-adc","mechanism":"Impaired internalisation / lysosomal processing","category":"pharmacology"},{"class":"cdk46-endocrine","mechanism":"RB1 loss","category":"bypass"}],"licence":"CC BY-NC 4.0, attribution to OnCo (https://onco.cc); commercial use needs a licence"}