Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Regulatory requirements for histology independent indications in oncology ***

Dr. Hilke Zander (Abschlußjahr: 2020)

Summary
Language: English
Traditionally, classification of cancers is based on their histology and anatomical location. With the approvals of pembrolizumab for the treatment of patients with MSI-H and dMMR tumors and larotrectinib for the treatment of patients with NTRK fusion tumors in 2017 and 2019 by the FDA and larotrectinib by the EMA in 2019,  a paradigm shift in biomarker guided cancer drug development was initiated.  Considering this milestone in cancer drug development, the objective of this master thesis is to describe the regulatory view on this paradigm shift. After providing some fundamental definitions, this thesis analyses the two histology independent applications. Differences in the requirements and challenges between both approvals are highlighted. Basic requirements for histology independent indications are an unmet medical need, an established tumor tissue independent Mode of Action, a validated biomarker, a clinical proof of principle with demonstrated activity across tumor types, and a manageable safety profile. Histology independent drug development is still exceptional and histology independent therapies challenge the existing market entry pathways and regulatory frameworks.  Nevertheless, with the approval of pembrolizumab (FDA) and larotrectinib (FDA and EMA), the agencies clearly stated that they are willing to prioritize cancer drugs that target tumors according to their genetic design rather than where they originate in the body.  Dependent on the biological rationale and the comprehensiveness of preclinical data, histology independent drug development could be considered in future clinical testing strategies.
Pages: 58,
Annexes: 01, Pages: 5