The study convincingly shows that EGFR-targeting transTACs efficiently trigger EGFR degradation of varying mutational status even more effective than the respective TKI (afatinib, gefitinib or osimertinib) based targeted therapies, as shown in a non-small cell lung cancer (NSCLC) model and in in vivo testing, demonstrating proper tumor targeting and efficient tumor growth inhibition. Here, EGFR is linked to non-small cell lung carcinoma.