Fig. 8: Stability and pharmacokinetic/toxicokinetic data of GQ1005.
A, B Dynamic changes of the drug-to-antibody ratios (DAR) of GQ1005 and T-DXd (A) ex vivo in plasma and (B) in vivo in circulation in cynomolgus monkeys (n = 3 per group). GQ1005 demonstrated good stability both ex vivo and in vivo when compared to T-DXd, whose DAR nearly halved within 4 days in plasma and 5 days in circulation, respectively. C, D Payload enrichment in tumor and plasma of NCI-N87 human gastric cancer-bearing BALB/c nude mice for GQ1005 versus T-DXd (n = 3 per group). Despite lower DAR, GQ1005 demonstrated high payload enrichment in tumor, comparable to T-DXd, but had markedly lower payload exposure in plasma than T-DXd (AUC, 3.34 vs 22.1 h*ng/mL). The tumor-to-plasma payload exposure ratio for GQ1005 with enhanced linker stability was markedly higher than that for T-DXd (AUC, 198.5:1 vs 39.7:1). E–G Pharmacokinetic/toxicokinetic studies of single-dose intravenous GQ1005 infusion in cynomolgus monkeys (n = 6 per group). The mean serum DXd concentration was far lower than the mean serum GQ1005 ADC concentration. The serum DXd concentration in the 10 mg/kg group measured slightly higher than the lower limit of quantification (LLOQ) or was even unmeasurable. In the 30 and 90 mg/kg GQ1005 groups, the mean Cmax and AUC0-t for DXd remained low. H–J Pharmacokinetic study of repeated-dose intravenous GQ1005 administration in cynomolgus monkeys (n = 10 per group). The exposure level (AUC0-t) of GQ1005 ADC after repeated administration was similar to that after the first administration, indicating no drug accumulation. After repeated administration, the half-life t1/2 of GQ1005 ADC (4.04-6.65 days) and TAb (6.59-10.20 days) was comparable to that after the first administration. After the first and last administration, DXd was only detectable at certain timepoints in the 10 mg/kg GQ1005 group. With increasing dose, the timepoints where DXd was detectable gradually increased in the 30 and 60 mg/kg groups, with DXd concentrations slightly higher than the LLOQ. The average Cmax and AUC0-t of DXd increased with increasing dose of GQ1005 (30-60 mg/kg). In Figs. 8B, 8C & 8E–J, data are presented as mean values with standard deviations. Source data are provided as a Source Data file.
