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A side effect in an early trial severe enough (usually grade 3 or worse, or forcing a long treatment pause) that the dose cannot safely go higher. Counting DLTs at each dose level is how phase 1 trials find the maximum tolerated dose.
Protocols define DLTs in advance (typically grade ≥3 non-haematological toxicity, prolonged grade 4 neutropenia, febrile neutropenia, or inability to deliver a set fraction of planned dose) and observe them over a fixed window, usually the first cycle. If a pre-set proportion of patients at a dose (2 of 6 in a 3+3 design) have DLTs, that dose exceeds tolerance. The one-cycle window misses cumulative and late toxicities (neuropathy, ILD, ocular effects), a recognised limitation for continuously dosed targeted drugs and ADCs that Project Optimus and time-to-event designs aim to correct.
Shares CTCAE toxicity grading (grade 3-4 adverse events), Maximum tolerated dose (MTD), Therapeutic index (therapeutic window), Project Optimus.
Shares Maximum tolerated dose (MTD), Recommended phase 2 dose (RP2D), Therapeutic index (therapeutic window), Project Optimus.
Shares Recommended phase 2 dose (RP2D), Dose-escalation designs (3+3, BOIN, dose-expansion).
Shares Dose-escalation designs (3+3, BOIN, dose-expansion), Project Optimus.
Shares Maximum tolerated dose (MTD), Dose-escalation designs (3+3, BOIN, dose-expansion).
Shares Dose-escalation designs (3+3, BOIN, dose-expansion), Project Optimus.
Shares Dose-escalation designs (3+3, BOIN, dose-expansion), Project Optimus.