PCA062

PCA062 is an antibody-drug conjugate (ADC) developed to target P-cadherin (CDH3), a cell surface glycoprotein highly expressed in several malignancies, including breast, esophageal, head and neck, bladder, and lung cancers. The drug consists of a human IgG1 monoclonal antibody specific for P-cadherin conjugated via a non-cleavable thioether linker (SMCC) to the cytotoxic payload DM1 (a maytansinoid tubulin inhibitor). Upon binding to P-cadherin-expressing tumor cells and internalization into lysosomes, the DM1 payload is released intracellularly where it disrupts microtubule dynamics leading to mitotic arrest and apoptosis. Preclinical studies showed potent antitumor activity in models of P-cadherin–expressing cancers. In clinical trials, PCA062 was administered intravenously every two weeks; however, development was discontinued by Novartis due to limited efficacy at the maximum tolerated dose despite manageable toxicity[1][2][3][4][5][6].