Payload (ADC)
The payload is the poison an ADC carries, usually a chemotherapy far too toxic to give on its own.
The payload is the cytotoxic warhead conjugated to the antibody. Classes: tubulin inhibitors (MMAE, MMAF, DM1, DM4), topoisomerase-I inhibitors (DXd, SN-38, exatecan, belotecan derivatives), DNA-damaging agents (PBD dimers, calicheamicin, duocarmycin). Newer payloads: degraders, immune agonists, radionuclides. Membrane permeability determines bystander killing.
Almost every patient newly diagnosed with advanced bladder or urothelial cancer should now be offered enfortumab vedotin plus pembrolizumab rather than chemotherapy, with median survival extended from about 16 months to over two and a half years. Neuropathy and skin toxicity need monitoring and dose adjustment, and patients with severe diabetes or pre-existing neuropathy need care. Platinum chemotherapy remains an option for those who cannot receive the combination.
For HER2-positive metastatic breast cancer that has progressed after trastuzumab and a taxane, trastuzumab deruxtecan is now the standard second-line treatment and T-DM1 has moved later in the sequence. The benefit is large enough that ADC design, not just the target, is understood to be what matters. Patients need lung monitoring because of the risk of pneumonitis.
Sacituzumab govitecan is a standard second-line or later treatment for metastatic triple-negative breast cancer, roughly doubling survival compared with the chemotherapies it was tested against. Patients should expect neutropenia and diarrhoea, which are manageable with growth factor support and loperamide. Trials are now testing it earlier, in first-line combinations with pembrolizumab and after surgery for residual disease.