Learn and practice PK/PD modelling for antibody-drug conjugates Until now, the ADC has usually used a sequential method to build up the PopPK model. Here, I would like to learn and practice or even summarize the characteristics of these ADC PopPK models. Welcome all the others who are interested in discussing this topic.
1. Troldelvy (FDA first indication's review documents: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/761115Orig1s000TOC.cfm)
Sacituzumab govitecan contains a humanized monoclonal antibody hRS7 IgG1 which targets Trop-2. The antibody portion is linked to SN-38, the small molecule portion, via a hydrolysable linker. Sacituzumab govitecan induces DNA damage, leading to apoptosis.
For adult patients who have received at least two prior systemic therapies, with at least one therapy for metastatic disease.
For adult patients who have previously received platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor.
sacituzumab govitecan is administered as an intravenous (IV) infusion.
The mean volume of distribution of sacituzumab govitecan is 0.045 L/kg.
UGT1A1 is involved in the metabolism of SN-38, the small molecule portion of sacituzumab govitecan, to form SN-38 glucuronide (SN-38G).
the mean terminal half-life of sacituzumab govitecan is 16 hours and SN-38 is 18 hours.
Citation: Sathe, A.G., Singh, I., Singh, P. et al. Population Pharmacokinetics of Sacituzumab Govitecan in Patients with Metastatic Triple-Negative Breast Cancer and Other Solid Tumors. Clin Pharmacokinet 63, 669–681 (2024). https://doi.org/10.1007/s40262-024-01366-3
Scientists from Gilead Sciences, Inc. published this paper: "Three population pharmacokinetic models were constructed using non-linear mixed-effects modeling; clinically relevant covariates were evaluated to assess their impact on exposure. Models for SG and tAB were developed independently whereas free SN-38 was sequentially generated via a first-order release process from SG."