Assessment of chemical stability of monoclonal antibody and antibody drug conjugate administered by pressured intraperitoneal aerosol chemotherapy
3 October 2024
G. Galy1, V. D’Atri2, M. Buff2, M. Imiolek3, M Hübner4, S. Intidhar Labidi-Galy5, D. Guillarme2, L. Carrez11 Service Pharmacie, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Suisse
2 Institut des Sciences Pharmaceutiques de Suisse occidentale, Université de Genève, CMU Genève, Suisse
3 Waters Corporation, Genève, Suisse
4 Service de chirurgie viscérale, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Université de Lausanne (UNIL)
5 Département d’oncologie, Hôpitaux Universitaires de Genève, Genève, Suisse
Introduction
Pressured intraperitoneal aerosol chemotherapy (PIPAC) is a new therapeutic approach for patients with peritoneal cancer. So far, most published studies investigated the administration of established cytostatic agents through PIPAC. This study aimed to evaluate the effect of PIPAC on two breakthrough anti-cancer agents, specifically anti-PD1 pembrolizumab, and anti-HER2 antibody-drug conjugate (ADC) - trastuzumab-deruxtecan.
Methods
We conducted systematic analyses on samples of pembrolizumab and trastuzumab-deruxtecan at clinically relevant concentrations before and after PIPAC administration using an experimental setup of hermetic container system, mimicking the abdominal cavity and by use of identical features as in clinical use.
We utilized a range of chromatographic and spectroscopic techniques to explore potential alterations in the primary, secondary, and tertiary structures of the drugs, focusing on post-translational modifications resulting from the aerosolization.
Results and Discussion
Our findings indicate that PIPAC did not compromise the integrity of tested biopharmaceuticals. The size variants of both drugs, assessed by size exclusion chromatography (SEC), remained unchanged. Reversed phase liquid chromatography (RPLC) and hydrophobic interaction chromatography (HIC) revealed no significant differences in hydrophobicity variants, average drug to antibody ratio (DAR), or DAR distribution before and after PIPAC treatment. Circular dichroism (CD) spectroscopy confirmed that the secondary and tertiary structures were preserved.
While pembrolizumab showed no change in charge variants post-PIPAC, trastuzumab-deruxtecan exhibited a non-negligible change in the quantity of charge variants on the monoclonal antibody itself, while the payload remains unchanged. This shift could possibly be related to the metallic composition of the Capnopen® device (made of nickel and chromium) used in PIPAC and for these experiments.
Conclusion
Together, our results suggest that PIPAC does not alter the structure of pembrolizumab and trastuzumab-deruxtecan, paving the way for future clinical trials.