# ADC for residual disease after KEYNOTE-522

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

## TL;DR

Patients whose TNBC survives chemo-immunotherapy before surgery have a high relapse risk. Give them an ADC after surgery.

## Summary

Patients whose TNBC survives neoadjuvant chemo-immunotherapy carry a high relapse risk, and this idea gives them a TROP2 ADC, with or without pembrolizumab, after surgery. It applies the KATHERINE model, T-DM1 for HER2-positive residual disease, to TNBC with residual cancer burden after KEYNOTE-522 therapy. Residual disease is chemoresistant but not necessarily ADC-resistant, because the payload is delivered at concentrations chemotherapy cannot reach. The concept is being tested at scale in ASCENT-05 with sacituzumab govitecan plus pembrolizumab and in TROPION-Breast03 with datopotamab deruxtecan, and ctDNA-defined high-risk subgroups should be pre-specified. It forms part of the TNBC roadmap.

## Fields

- Kind: Idea
- Last checked: 2026-09-04
- Hypothesis: Adjuvant TROP2 ADC ± pembrolizumab improves iDFS in TNBC with residual disease (RCB I-III) after neoadjuvant KEYNOTE-522 therapy compared with pembrolizumab ± capecitabine.
- Rationale: Residual disease is chemoresistant but not necessarily ADC-resistant; ADC payload is delivered at concentrations chemotherapy cannot reach.
- Proposed test: ASCENT-05 and TROPION-Breast03 readouts expected 2026-27; ctDNA-defined high-risk subgroups should be pre-specified.
- Maturity: being-tested-at-scale

## Sources

- ClinicalTrials.gov NCT03036488: KEYNOTE-522: https://clinicaltrials.gov/study/NCT03036488

## Connected records

- cancers: [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/)
- drugs: [Datopotamab deruxtecan](https://onco.cc/drugs/datopotamab-deruxtecan/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Sacituzumab govitecan](https://onco.cc/drugs/sacituzumab-govitecan/)
- terms: [Pathologic complete response (pCR)](https://onco.cc/terms/pcr/), [Residual cancer burden (RCB)](https://onco.cc/terms/rcb/)
- trials: [ASCENT-05 / OptimICE-RD (AFT-65, GBG 119, NSABP B-63)](https://onco.cc/trials/ascent-05/), [KEYNOTE-522](https://onco.cc/trials/keynote-522/), [TROPION-Breast03](https://onco.cc/trials/tropion-breast03/)
- key papers: [ASCENT: sacituzumab govitecan doubles survival in heavily pretreated metastatic triple-negative breast cancer](https://onco.cc/key-papers/paper-ascent-nejm-2021/), [KATHERINE: switching to T-DM1 when HER2-positive breast cancer survives pre-surgery treatment](https://onco.cc/key-papers/paper-katherine-nejm-2019/), [KEYNOTE-522: adding pembrolizumab before and after surgery in early triple-negative breast cancer](https://onco.cc/key-papers/paper-keynote-522-nejm-2022/), [Pembrolizumab for Early Triple-Negative Breast Cancer](https://onco.cc/key-papers/paper-keynote-522-n-engl-j-med-2020/), [Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial](https://onco.cc/key-papers/paper-keynote-355-lancet-2020/)
- roadmaps: [TNBC roadmap: from 'nothing to target' to ADC + immunotherapy first line](https://onco.cc/roadmaps/tnbc-history/)

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