Hospital in-use evaluation of the physical, chemical and affinity stability of the antibody-drug conjugate trastuzumab deruxtecan (Enhertu®)

More and more expensive antineoplastic therapies such as antibody-drug conjugates (ADCs) are being marketed worldwide. To ease the burden on the healthcare system, it is therefore important to optimize their use from preparation to administration. In hospital drug preparation units, the use of vials leads to waste as dosages are expressed in milligrams per kilograms. In the case of trastuzumab deruxtecan (Enhertu® or T-DXd), reconstituted vial leftovers are thrown away after 48 hours, resulting in considerable economic losses. In this study, physical (SEC-UV, DLS, nano-DSF), chemical (LC-HRMS) and affinity (ELISA, BLI) analyses are used to compare different post-reconstitution study times to the < 48 hours reconstituted T-DXd. This hospital stability in-use study is the first to be conducted on an ADC. We demonstrated on reconstituted T-DXd that drug-to-antibody ratio of 8.0, HER-2 recognition, aggregation propensity, monomeric profile > 95 %, hydrodynamic diameter (∼ 13.6 nm) and polydispersity index (< 0.15) remain similar for up to 4 weeks. These results support stability for up to 4 weeks post-reconstitution under our analysis conditions and under appropriate preparation and storage conditions (2-8°C). T-DXd is a blockbuster breast cancer therapy showing excellent results in many clinical trials, so for economic reasons, its use should be rationalized in the future.