# Neoadjuvant ADC + IO replacing anthracycline chemotherapy in TNBC

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

## TL;DR

Replace the toughest part of pre-surgery chemotherapy with an ADC plus immunotherapy, aiming for the same cure rate with less harm.

## Summary

This idea replaces the anthracycline part of pre-surgery chemotherapy in TNBC with a TROP2 ADC plus pembrolizumab, aiming for the same cure rate with less harm. The KEYNOTE-522 backbone carries cardiac and leukaemia risk from anthracyclines, while ADCs deliver the same chemotherapy class more selectively and ADC-induced immunogenic death complements checkpoint blockade. Sacituzumab govitecan and datopotamab deruxtecan with pembrolizumab already show activity in metastatic disease and in the NeoSTAR and I-SPY 2 arms. The test is a randomised phase 3 against the KEYNOTE-522 regimen with pathologic complete response and then event-free survival endpoints. At early-clinical maturity it bears on the ADC plus checkpoint inhibitor pairing and the SCARLET trial.

## Fields

- Kind: Idea
- Last checked: 2026-09-04
- Hypothesis: Neoadjuvant TROP2 ADC + pembrolizumab achieves non-inferior pCR and EFS to KEYNOTE-522 with fewer grade 3+ toxicities.
- Rationale: ADC payloads are the same chemotherapy class delivered more selectively; ADC-induced immunogenic death complements pembrolizumab.
- Proposed test: Randomised phase 3 versus KEYNOTE-522 regimen with pCR then EFS endpoints; TIL-high and HER2-low subgroups pre-specified.
- Maturity: early-clinical

## Sources

- ClinicalTrials.gov NCT03036488: KEYNOTE-522: https://clinicaltrials.gov/study/NCT03036488
- ClinicalTrials.gov NCT05929768: SCARLET (SWOG S2212): https://clinicaltrials.gov/study/NCT05929768

## Connected records

- pairings: [ADC + checkpoint inhibitor](https://onco.cc/pairings/adc-plus-io/)
- cancers: [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- drugs: [Datopotamab deruxtecan](https://onco.cc/drugs/datopotamab-deruxtecan/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Sacituzumab govitecan](https://onco.cc/drugs/sacituzumab-govitecan/)
- trials: [KEYNOTE-522](https://onco.cc/trials/keynote-522/), [SCARLET (SWOG S2212)](https://onco.cc/trials/scarlet-s2212/)
- key papers: [ASCENT: sacituzumab govitecan doubles survival in heavily pretreated metastatic triple-negative breast cancer](https://onco.cc/key-papers/paper-ascent-nejm-2021/), [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/)

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