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Antibody-drug conjugates deliver chemotherapy payloads into tumours but cause lung, eye and nerve damage that tracks total exposure, and several were approved without an optimised dose. Randomised comparisons of lower doses, longer intervals and capped cumulative payload could keep the benefit while cutting these harms.
Randomised dose and schedule comparisons for ADCs (e.g., lower dose per cycle, extended intervals, capped cumulative payload dose, response-adapted de-escalation) with PK of conjugate and free payload, tolerability estimands (ILD, ocular toxicity, neuropathy) and efficacy. The 5.4 versus 6.4 mg/kg trastuzumab deruxtecan comparison and dose modifications for several approved ADCs show dose was not optimised at approval.
Shares Mirvetuximab soravtansine, Enfortumab vedotin, Sacituzumab govitecan, Trastuzumab deruxtecan.
Shares Payload (ADC), Enfortumab vedotin, Trastuzumab deruxtecan, Antibody-drug conjugate (ADC).
Shares Interstitial lung disease (ILD) / pneumonitis, Wrong doses, Trastuzumab deruxtecan, Antibody-drug conjugate (ADC).
Shares Interstitial lung disease (ILD) / pneumonitis, Payload (ADC), Toxicity and quality of life are undervalued, Antibody-drug conjugate (ADC).
Shares Interstitial lung disease (ILD) / pneumonitis, Sacituzumab govitecan, Trastuzumab deruxtecan, Antibody-drug conjugate (ADC).
Shares Payload (ADC), Sacituzumab govitecan, Trastuzumab deruxtecan, Antibody-drug conjugate (ADC).
Shares Wrong doses, Trastuzumab deruxtecan, Toxicity and quality of life are undervalued, Antibody-drug conjugate (ADC).
Shares Drug-to-antibody ratio (DAR), Interstitial lung disease (ILD) / pneumonitis, Payload (ADC), Trastuzumab deruxtecan.