Masterarbeit

Developments in anticancer immunotherapies for use in combination ***

Dr. Verena Schummer (2013)

Summary

Language: English

Despite the progress in the development of anticancer therapies, most cancer diseases have a high mortality and morbidity. Although many new therapeutic approaches have been found during the last years, the clinical efficacy for patients with advanced cancer stages remains low. There is increasing information on the clinical efficacy of anticancer immunotherapies including therapeutic vaccines and there are promising results from clinical trials combining different immunotherapies or immunotherapies with conventional cytotoxic drugs.

The scope of this master thesis is to analyse regulatory aspects of anticancer combination immunotherapies on the basis of available guidelines and experience from clinical trial applications. The underlying biological effects are discussed as well as the potential benefits and risks using the examples of published clinical studies.

Immunotherapies combined with chemo- and/or radiotherapy or with other immunotherapies can provide benefits in the treatment of tumour patients with regard to safety as well as efficacy. Synergistic and complementary biological effects can be seen in case the doses and treatment intervals are chosen in an optimal way.

For the choice of a correct study design, the EMA as well as the FDA provide some guidance documents. The EU guidelines only give broad recommendations on the starting dose finding and the choice of comparators, whereas the FDA guidelines contain slightly more detailed requirements to be fulfilled by the sponsor which means that combinations must be justified (based on preclinical data), and that a rationale must be provided for the study design as well as the dose selection.

When analysing clinical trial applications in which immunotherapies are combined with other anticancer treatments, preclinical rationales are considered important to define doses, treatment schedules and potential toxic effects. Literature data underlines this need for thorough preclinical investigations as enhanced toxic effects were seen in combination studies even though the single substances were already approved.

The most important challenges using anticancer immunotherapies in combination with other antitumour therapies seem to be the definition of the optimal treatment regimen including optimal doses and dosing schedules. Only few guidance is available for the development of immunotherapies in combination use, and it could therefore be helpful to standardise the requirements in order to facilitate the establishment of safe and efficacious doses and treatment schedules.

Pages: 52, Annexes: pages: 0