# TROP2 PET to choose and sequence TROP2 ADCs

Source: https://onco.cc/ideas/idea-trop2-pet-selection/  
OnCo record `idea-trop2-pet-selection` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-04
- 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.
- Proposed 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

## Sources

- ASCENT: sacituzumab govitecan doubles survival in heavily pretreated metastatic triple-negative breast cancer (New England Journal of Medicine 2021): https://doi.org/10.1056/NEJMoa2028485

## Connected records

- pairings: [PSMA PET → PSMA radioligand therapy](https://onco.cc/pairings/psma-pet-to-rlt/), [TROP2 PET → TROP2 ADC selection](https://onco.cc/pairings/trop2-pet-to-adc/)
- cancers: [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Immuno-PET](https://onco.cc/technologies/immuno-pet/), [TROP2 PET](https://onco.cc/technologies/trop2-pet/)
- targets: [TROP2](https://onco.cc/targets/trop2/)
- drugs: [Datopotamab deruxtecan](https://onco.cc/drugs/datopotamab-deruxtecan/), [Sacituzumab govitecan](https://onco.cc/drugs/sacituzumab-govitecan/), [Sacituzumab tirumotecan](https://onco.cc/drugs/sacituzumab-tirumotecan/)
- trials: [ASCENT](https://onco.cc/trials/ascent/), [ASCENT-03](https://onco.cc/trials/ascent-03/), [ASCENT-04 / KEYNOTE-D19](https://onco.cc/trials/ascent-04/), [TROPION-Breast02](https://onco.cc/trials/tropion-breast02/), [TROPION-Lung01](https://onco.cc/trials/tropion-lung01/)
- key papers: [ASCENT: sacituzumab govitecan doubles survival in heavily pretreated metastatic triple-negative breast cancer](https://onco.cc/key-papers/paper-ascent-nejm-2021/), [Efficacy and Safety of Anti-Trop-2 Antibody Drug Conjugate Sacituzumab Govitecan (IMMU-132) in Heavily Pretreated Patients With Metastatic Triple-Negative Breast Cancer](https://onco.cc/key-papers/paper-sacituzumab-govitecan-tnbc-j-clin-oncol-2017/), [Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer](https://onco.cc/key-papers/paper-sacituzumab-govitecan-tnbc-n-engl-j-med-2019/), [TROPION-Breast01: datopotamab deruxtecan versus chemotherapy in pretreated hormone-receptor-positive breast cancer, and why a PFS win did not translate to survival](https://onco.cc/key-papers/paper-tropion-breast01-jco-2024/)
- roadmaps: [TROP2 ADC roadmap: sacituzumab govitecan → Dato-DXd → sac-TMT → bispecifics and PET](https://onco.cc/roadmaps/trop2-adc-roadmap/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/)

---
JSON: https://onco.cc/api/v1/entities/idea-trop2-pet-selection.json