Therapeutic index (therapeutic window)
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.
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not linked directly; found by shared links- TermRecommended phase 2 dose (RP2D)
Shares Pharmacokinetics (PK), half-life and exposure, Dose-limiting toxicity (DLT), Maximum tolerated dose (MTD), Project Optimus.
- TermDose-escalation designs (3+3, BOIN, dose-expansion)
Shares Dose-limiting toxicity (DLT), Maximum tolerated dose (MTD), Project Optimus.
- TermCTCAE toxicity grading (grade 3-4 adverse events)
Shares Dose-limiting toxicity (DLT), Dose reduction, interruption and discontinuation.
- TermFebrile neutropenia
Shares Dose-limiting toxicity (DLT), Dose reduction, interruption and discontinuation.
- IdeaLinked human organ chips to predict side effects before people are dosed
Shares Interstitial lung disease (ILD) / pneumonitis, Antibody-drug conjugate (ADC).
- IdeaTest flat versus weight-based dosing of antibodies, and use dose banding to cut waste
Shares Interstitial lung disease (ILD) / pneumonitis, Antibody-drug conjugate (ADC).
- ProductBelantamab mafodotin
Shares Ocular toxicity (keratopathy, blurred vision), Antibody-drug conjugate (ADC).
- IdeaDose and schedule optimisation trials specific to antibody-drug conjugates
Shares Interstitial lung disease (ILD) / pneumonitis, Antibody-drug conjugate (ADC).