OnCo
ideasIdea

Neoadjuvant ADC + IO replacing anthracycline chemotherapy in TNBC

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

KEYNOTE-522's backbone includes anthracyclines with cardiac and leukaemia risk. ADCs + pembrolizumab achieve high response rates in metastatic disease; NeoSTAR (sacituzumab) and I-SPY 2 arms show meaningful pCR rates.

Confidence
40%65%likelyOnCo editors (initial estimate), 2026-09-07 · High metastatic response rates and I-SPY signals support it; anthracycline omission is the risk.
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.
What would test it
Randomised phase 3 versus KEYNOTE-522 regimen with pCR then EFS endpoints; TIL-high and HER2-low subgroups pre-specified.
Maturity
early clinical

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