# ADC sequencing

Source: https://onco.cc/terms/adc-sequencing/  
OnCo record `adc-sequencing` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The open question of whether a second ADC works after the first one fails, especially when both carry the same type of payload.

## Summary

ADC sequencing is the open question of whether a second antibody-drug conjugate works after the first one fails, especially when both carry the same class of payload. Retrospective series including SATEEN, BRE-354 and data at ESMO Breast 2026 show reduced efficacy when a second TOP1-payload ADC follows immediately after the first; proposed mechanisms are SLFN11 loss, TOP1 mutations, efflux and antigen downregulation. Prospective trials such as TRADE-DXd are under way. The term is attached to Triple-negative breast cancer (TNBC) and HR-positive / HER2-negative breast cancer and to the Antibody-drug conjugate (ADC) technology, and it is referenced by Mersana Therapeutics, the pairing cautioning against TOP1 ADC after TOP1 ADC and the idea of payload-class switching.

## Fields

- Kind: Term
- Last checked: 2026-09-04

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Antibody-drug_conjugate
- Wikipedia: https://en.wikipedia.org/wiki/Antibody-drug_conjugate

## Connected records

- cancers: [HER2-positive breast cancer](https://onco.cc/cancers/breast-her2-positive/), [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Topoisomerase-I inhibitors (and ADC payloads)](https://onco.cc/technologies/topoisomerase-inhibitors/)
- ideas: [A randomised trial of antibody-drug conjugate sequence in metastatic triple-negative breast cancer](https://onco.cc/ideas/idea-tnbc-adc-sequencing-trial/), [A real-world sequencing analysis within a year of every new approval](https://onco.cc/ideas/idea-data-sequencing-analysis-per-approval/), [A registry of every treatment sequence patients actually receive, with outcomes](https://onco.cc/ideas/idea-tr2-sequence-registry/), [Multi-arm, multi-stage trials to answer which order to give approved drugs](https://onco.cc/ideas/idea-tr1-mams-for-sequencing-questions/), [Payload-class switching as the rule for ADC sequencing](https://onco.cc/ideas/idea-payload-switching/), [Randomise the next line of treatment before the first one fails](https://onco.cc/ideas/idea-bio1-pre-randomised-sequencing-trials/), [Registry-embedded randomisation of treatment order in routine care](https://onco.cc/ideas/idea-tr2-pragmatic-sequence-randomisation/), [Sequence folate-receptor ADCs by payload class](https://onco.cc/ideas/idea-fra-adc-sequencing-ovarian/), [Sequencing HER2 ADCs by payload after T-DXd](https://onco.cc/ideas/idea-her2-adc-sequencing-payload/), [Sequential multiple-assignment randomised trials to find the best order of ADCs](https://onco.cc/ideas/idea-tr2-smart-sequencing-adc/), [Use SLFN11 status to decide which antibody-drug payload to give next](https://onco.cc/ideas/idea-bio1-slfn11-payload-guidance/)
- key papers: [Datopotamab deruxtecan in patients with untreated, advanced triple-negative breast cancer (TROPION-Breast02): a randomised, open-label, international, phase III trial](https://onco.cc/key-papers/paper-tropion-breast02-ann-oncol-2026/), [DESTINY-Breast03: trastuzumab deruxtecan beats T-DM1 as second-line treatment of HER2-positive metastatic breast cancer](https://onco.cc/key-papers/paper-destiny-breast03-nejm-2022/), [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: [ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs](https://onco.cc/roadmaps/adc-generations/), [Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem](https://onco.cc/roadmaps/tnbc-roadmap/), [TROP2 ADC roadmap: sacituzumab govitecan → Dato-DXd → sac-TMT → bispecifics and PET](https://onco.cc/roadmaps/trop2-adc-roadmap/)
- companies: [Mersana Therapeutics](https://onco.cc/companies/mersana/)
- pairings: [Caution: TOP1 ADC immediately after TOP1 ADC](https://onco.cc/pairings/adc-after-adc-caution/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [Too many combinations to test](https://onco.cc/bottlenecks/b-combination-space/)
- terms: [Cross-resistance](https://onco.cc/terms/cross-resistance/), [Exatecan (and derivatives)](https://onco.cc/terms/exatecan/), [Topoisomerase-I inhibitor payloads](https://onco.cc/terms/topoisomerase-i-payloads/)
- pathways: [Drug efflux pumps (ABC transporters)](https://onco.cc/pathways/drug-efflux-pumps/)

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