# EGFR TKI → ADC on progression

Source: https://onco.cc/pairings/tki-then-adc-lung/  
OnCo record `tki-then-adc-lung` (Pairing). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

After the lung cancer pill stops working, an ADC that does not care which resistance mutation emerged.

## Summary

This sequence pairing follows an EGFR tyrosine kinase inhibitor, Osimertinib, with an antibody-drug conjugate, Datopotamab deruxtecan, on progression in EGFR-mutant Non-small-cell lung cancer: after the pill stops working, an ADC that does not care which resistance mutation emerged takes over. The rationale is that resistance to TKIs is heterogeneous (C797S, MET, histologic transformation), and ADCs bypass genotype by exploiting antigen expression instead. Datopotamab deruxtecan was approved in 2025 after osimertinib and chemotherapy on phase 3 data, and Patritumab deruxtecan (HER3-DXd) and Izalontamab brengitecan (iza-bren) target the same setting. Amivantamab plus chemotherapy, tested in MARIPOSA-2, is the alternative strategy at this point in the sequence.

## Fields

- Kind: Pairing
- Last checked: 2026-09-04
- Pairs: Osimertinib + Datopotamab deruxtecan
- Type: sequence
- Rationale: Resistance to TKIs is heterogeneous (C797S, MET, transformation); ADCs bypass genotype by exploiting antigen expression.
- Evidence: Approval; phase 3 data.

## Sources

- HERTHENA-Lung01: patritumab deruxtecan in EGFR-mutated NSCLC after EGFR TKI (Journal of Clinical Oncology 2023): https://doi.org/10.1200/JCO.23.01476

## Connected records

- cancers: [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- drugs: [Amivantamab](https://onco.cc/drugs/amivantamab/), [Datopotamab deruxtecan](https://onco.cc/drugs/datopotamab-deruxtecan/), [Izalontamab brengitecan](https://onco.cc/drugs/izalontamab-brengitecan/), [Osimertinib](https://onco.cc/drugs/osimertinib/), [Patritumab deruxtecan](https://onco.cc/drugs/patritumab-deruxtecan/)

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