Enhertu (fam-trastuzumab deruxtecan): how was the first human dose set?

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Enhertu: how was the first human dose set?

fam-trastuzumab deruxtecan · HER2

First-in-human starting dose

1/12 HED of monkey HNSTD (0.8 mg/kg), also matching minimum effective trough concentration

“The FIH dose of 0.8 mg/kg was selected based on one-twelfth of the human equivalent dose of the highest non-severely toxic dose (HNSTD) in cynomolgus monkeys in toxicology studies and was also estimated to provide trough concentration in humans comparable to the minimum effective concentrations in nonclinical studies.”

✓ VerifiedFDA multi-discipline review, p. 80Source ↗

NOAEL / key findings

HNSTD 30 mg/kg monkey, 197 mg/kg rat; bone marrow, intestine, skin, lung, testis, kidney; lung toxicity at 78.8 mg/kg

“The highest non-severely toxic dose of trastuzumab deruxtecan was established at 197 mg/kg in rats (non-binding species), and 30 mg/kg in cynomolgus monkey”

✓ VerifiedEMA assessment report, p. 49Source ↗

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Enhertu: how was the first human dose set?

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