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Their integration into third line as monotherapy, and now second line in combination, as well as recent data in the first line underscores their therapeutic potential. The efficacy of bispecific antibodies depends on sustained target antigen expression and preserved T\u2010cell function; the loss of either of these factors, or intrinsic tumour and microenvironment biology, contributes to therapeutic resistance. Combination strategies aim to overcome these resistance mechanisms, enhance anti\u2010tumour efficacy and potentially reduce treatment\u2010related adverse events. In this review, we critically examine the current understanding of TCE resistance and discuss how this informs combination strategies. 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