Clinical pharmacology strategies to accelerate the development of polatuzumab vedotin and summary of key findings

• Published in: Advanced drug delivery reviews 2024-04, Vol.207, p.115193, Article 115193
• Main Authors: Liao, Michael Z., Lu, Dan, Lu, Tong, Gibiansky, Leonid, Deng, Rong, Samineni, Divya, Dere, Randall, Lin, Andy, Hirata, Jamie, Shen, Ben-Quan, Zhang, Donglu, Li, Dongwei, Li, Chunze, Miles, Dale
• Format: Article
• Language: English
• Subjects: Antibody–drug conjugate; Diffuse large B-cell lymphoma; Modeling; Monomethyl auristatin E; non-Hodgkin lymphoma; Pharmacokinetics
• ISSN: 0169-409X; 1872-8294; 1872-8294
• DOI: 10.1016/j.addr.2024.115193

[Display omitted] The favorable benefit–risk profile of polatuzumab vedotin, as demonstrated in a pivotal Phase Ib/II randomized study (GO29365; NCT02257567), coupled with the need for effective therapies in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), prompted the need to accelerate polatuzumab vedotin development. An integrated, fit-for-purpose clinical pharmacology package was designed to support regulatory approval. To address key clinical pharmacology questions without dedicated clinical pharmacology studies, we leveraged non-clinical and clinical data for polatuzumab vedotin, published clinical data for brentuximab vedotin, a similar antibody–drug conjugate, and physiologically based pharmacokinetic and population pharmacokinetic modeling approaches. We review strategies and model-informed outcomes that contributed to regulatory approval of polatuzumab vedotin plus bendamustine and rituximab in R/R DLBCL. These strategies made polatuzumab vedotin available to patients earlier than previously possible; depending on the strength of available data and the regulatory/competitive environment, they may also prove useful in accelerating the development of other agents.