{"entity":{"id":"idea-trop2-pet-selection","kind":"idea","name":"TROP2 PET to choose and sequence TROP2 ADCs","aka":[],"tldr":"Use a whole-body TROP2 scan instead of a single tissue stain to decide which patients get a TROP2 ADC, which one, and when to switch.","summary":"The proposal is to use a whole-body TROP2 PET scan, rather than a single tissue stain, to decide which patients receive a TROP2 ADC, which agent they get and when to switch. Baseline uptake and heterogeneity would predict benefit, and a fall in uptake at progression would signal antigen loss that should prompt a move to a non-TROP2 ADC rather than a second TROP2 agent. IHC on archival tissue failed to predict sacituzumab govitecan benefit, whereas PSMA PET already plays this role for Pluvicto and 89Zr-antibody and 68Ga-nanobody tracers image human tumours. The test is an imaging sub-study inside a first-line TNBC ADC trial, then a randomised PET-guided versus standard sequencing trial. At early-clinical maturity, it bears on the bottleneck Biomarkers are not validated or standardised.","asOf":"2026-09-04","links":[{"label":"ASCENT: sacituzumab govitecan doubles survival in heavily pretreated metastatic triple-negative breast cancer (New England Journal of Medicine 2021)","url":"https://doi.org/10.1056/NEJMoa2028485"}],"tags":[],"related":["trop2-pet-to-adc","psma-pet-to-rlt"],"cancers":["tnbc","nsclc"],"sections":[],"technologies":["trop2-pet","adc","immuno-pet"],"targets":["trop2"],"drugs":["sacituzumab-govitecan","datopotamab-deruxtecan","sacituzumab-tirumotecan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["ascent","ascent-03","ascent-04","tropion-breast02","tropion-lung01"],"people":[],"bottlenecks":[],"keyPapers":["paper-ascent-nejm-2021","paper-sacituzumab-govitecan-tnbc-n-engl-j-med-2019","paper-sacituzumab-govitecan-tnbc-j-clin-oncol-2017"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Baseline TROP2 PET uptake (SUV, heterogeneity index) predicts PFS on TROP2 ADCs better than IHC, and a fall in uptake at progression indicates antigen-loss resistance that should prompt a switch to a non-TROP2 ADC rather than a second TROP2 agent.","rationale":"PSMA PET does exactly this for Pluvicto. TROP2 is internalising and abundant; 89Zr-antibody and 68Ga-nanobody tracers already image human tumours.","test":"Prospective imaging sub-study in a first-line TNBC ADC trial (e.g., a TROPION-Breast05 or sac-TMT cohort) correlating baseline and on-treatment TROP2 PET with response and PFS; then a randomised PET-guided vs standard sequencing trial.","maturity":"early-clinical"},"route":"/ideas/idea-trop2-pet-selection/","neighbours":{"pairing":[{"id":"psma-pet-to-rlt","kind":"pairing","name":"PSMA PET → PSMA radioligand therapy","route":"/pairings/psma-pet-to-rlt/"},{"id":"trop2-pet-to-adc","kind":"pairing","name":"TROP2 PET → TROP2 ADC selection","route":"/pairings/trop2-pet-to-adc/"}],"cancer":[{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"immuno-pet","kind":"technology","name":"Immuno-PET","route":"/technologies/immuno-pet/"},{"id":"trop2-pet","kind":"technology","name":"TROP2 PET","route":"/technologies/trop2-pet/"}],"target":[{"id":"trop2","kind":"target","name":"TROP2","route":"/targets/trop2/"}],"drug":[{"id":"datopotamab-deruxtecan","kind":"drug","name":"Datopotamab deruxtecan","route":"/drugs/datopotamab-deruxtecan/"},{"id":"sacituzumab-govitecan","kind":"drug","name":"Sacituzumab govitecan","route":"/drugs/sacituzumab-govitecan/"},{"id":"sacituzumab-tirumotecan","kind":"drug","name":"Sacituzumab tirumotecan","route":"/drugs/sacituzumab-tirumotecan/"}],"trial":[{"id":"ascent","kind":"trial","name":"ASCENT","route":"/trials/ascent/"},{"id":"ascent-03","kind":"trial","name":"ASCENT-03","route":"/trials/ascent-03/"},{"id":"ascent-04","kind":"trial","name":"ASCENT-04 / KEYNOTE-D19","route":"/trials/ascent-04/"},{"id":"tropion-breast02","kind":"trial","name":"TROPION-Breast02","route":"/trials/tropion-breast02/"},{"id":"tropion-lung01","kind":"trial","name":"TROPION-Lung01","route":"/trials/tropion-lung01/"}],"paper":[{"id":"paper-ascent-nejm-2021","kind":"paper","name":"ASCENT: sacituzumab govitecan doubles survival in heavily pretreated metastatic triple-negative breast cancer","route":"/key-papers/paper-ascent-nejm-2021/"},{"id":"paper-sacituzumab-govitecan-tnbc-j-clin-oncol-2017","kind":"paper","name":"Efficacy and Safety of Anti-Trop-2 Antibody Drug Conjugate Sacituzumab Govitecan (IMMU-132) in Heavily Pretreated Patients With Metastatic Triple-Negative Breast Cancer","route":"/key-papers/paper-sacituzumab-govitecan-tnbc-j-clin-oncol-2017/"},{"id":"paper-sacituzumab-govitecan-tnbc-n-engl-j-med-2019","kind":"paper","name":"Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer","route":"/key-papers/paper-sacituzumab-govitecan-tnbc-n-engl-j-med-2019/"},{"id":"paper-tropion-breast01-jco-2024","kind":"paper","name":"TROPION-Breast01: datopotamab deruxtecan versus chemotherapy in pretreated hormone-receptor-positive breast cancer, and why a PFS win did not translate to survival","route":"/key-papers/paper-tropion-breast01-jco-2024/"}],"roadmap":[{"id":"trop2-adc-roadmap","kind":"roadmap","name":"TROP2 ADC roadmap: sacituzumab govitecan → Dato-DXd → sac-TMT → bispecifics and PET","route":"/roadmaps/trop2-adc-roadmap/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"}]}}