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The gap between the dose that works and the dose that harms. Classic chemotherapy has a narrow window (the dose that kills the tumour nearly kills the patient); a wider window is the whole point of targeted drugs, ADCs and immunotherapy.
Toxicity can be on-target (the drug hits its intended molecule in normal tissue that also expresses it: EGFR inhibitors and skin, HER2 and heart, CD19 CAR-T and normal B cells, 'on-target off-tumour') or off-target (unintended molecules: hERG and QT prolongation, kinase promiscuity). ADCs widen the window by delivering payloads selectively, but the payload's free fraction sets their class effects (ILD for deruxtecan, ocular toxicity for MMAF, neuropathy for MMAE). Dose-finding in phase 1 traditionally sought the maximum tolerated dose; Project Optimus reframes it as finding the dose with the best therapeutic index, and tolerability over months of continuous therapy is now recognised as part of efficacy.
Showing the technology this term belongs to: Antibody-drug conjugate (ADC).
Shares Dose-limiting toxicity (DLT), Maximum tolerated dose (MTD), Pharmacokinetics (PK), half-life and exposure, Project Optimus.
Shares Maximum tolerated dose (MTD), Pharmacokinetics (PK), half-life and exposure, Project Optimus.
Shares Dose-limiting toxicity (DLT), Dose reduction, interruption and discontinuation.
Shares Dose-limiting toxicity (DLT), Maximum tolerated dose (MTD), Project Optimus.
Shares Ocular toxicity (keratopathy, blurred vision), Interstitial lung disease (ILD) / pneumonitis, Antibody-drug conjugate (ADC).
Shares Interstitial lung disease (ILD) / pneumonitis, Antibody-drug conjugate (ADC).
Shares Pharmacokinetics (PK), half-life and exposure, Dose reduction, interruption and discontinuation.
Shares Interstitial lung disease (ILD) / pneumonitis, Antibody-drug conjugate (ADC).