Dose and schedule optimisation trials specific to antibody-drug conjugates
Antibody-drug conjugates carry potent chemotherapy into tumours but also cause lung, eye and nerve damage that depends on total exposure. Trials comparing lower doses, longer intervals and payload caps 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.
- Wrong doses · Most drug doses were chosen as the highest a person can tolerate, which is often more than they need.
- Toxicity and quality of life are undervalued · Trials measure how long people live, not how they live. Side-effects are under-reported and under-treated.
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not linked directly; found by shared links- IdeaContinuous-flow synthesis of ultra-potent ADC payloads to ease the capacity squeeze
Shares Enfortumab vedotin, Payload (ADC), Trastuzumab deruxtecan, Antibody-drug conjugate (ADC).
- IdeaLinked human organ chips to predict side effects before people are dosed
Shares Interstitial lung disease (ILD) / pneumonitis, Payload (ADC), Toxicity and quality of life are undervalued, 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, Trastuzumab deruxtecan, Wrong doses, Antibody-drug conjugate (ADC).
- IdeaTumour-on-a-chip with blood flow to test whether big drugs actually get in
Shares Sacituzumab govitecan, Payload (ADC), Trastuzumab deruxtecan, Antibody-drug conjugate (ADC).
- IdeaReduce the dose once the cancer responds: response-adapted de-escalation trials
Shares Trastuzumab deruxtecan, Wrong doses, Toxicity and quality of life are undervalued, Antibody-drug conjugate (ADC).
- Key paperDESTINY-Breast03: trastuzumab deruxtecan beats T-DM1 as second-line treatment of HER2-positive metastatic breast cancer
Shares Drug-to-antibody ratio (DAR), Interstitial lung disease (ILD) / pneumonitis, Payload (ADC), Trastuzumab deruxtecan.
- TermDM4
Shares Mirvetuximab soravtansine, Payload (ADC), Antibody-drug conjugate (ADC).
- TermHydrophilic next-generation linkers (TMALIN, Dolaflexin, sulfonyl-pyrimidine, PEG-containing)
Shares Drug-to-antibody ratio (DAR), Antibody-drug conjugate (ADC).