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Review
. 2019 Mar;13(3):549-557.
doi: 10.1002/1878-0261.12465. Epub 2019 Feb 22.

New clinical trial designs in the era of precision medicine

Elena Garralda  1   2 , Rodrigo Dienstmann  1   3 , Alejandro Piris-Giménez  1 , Irene Braña  1   2 , Jordi Rodon  1   4 , Josep Tabernero  1
Affiliations
Review

New clinical trial designs in the era of precision medicine

Elena Garralda et al. Mol Oncol. 2019 Mar.

Abstract

Cancer treatment has made significant strides towards the promise of personalized medicine. Recent scientific advances have shown that there are numerous genetic deregulations that are common in multiple cancer types, raising the possibility of developing drugs targeting those deregulations irrespective of the tumour type. Precision Cancer Medicine (PCM) was born out of accumulated evidence matching targeted agents with these tumour molecular deregulations. At the same time, the therapeutic armamentarium is rapidly increasing and the number of new drugs (including immune-oncology agents) entering drug development continues to rise. These factors, added to strong collaboration with regulatory agencies, which have approved novel agents based on data obtained from phase 1/2 trials, have led to unprecedented evolution in the design of early-stage clinical trials. Currently, we have seen rapid phase 1 dose-escalation trials followed by remarkably large expansion cohorts, and are witnessing the emergence of new trials, such as adaptive studies with basket and umbrella designs aimed at optimizing the biomarker-drug co-development process. Alongside the growing complexity of these clinical trials, new frameworks for stronger and faster collaboration between all stakeholders in drug development, including academic institutions and frameworks, clinicians, pharma companies and regulatory agencies, have been established. In this review article, we describe the main challenges and opportunities that these new trial designs may provide for a more efficient drug development process, which may ultimately help ensure that PCM becomes a reality for patients.

Keywords: Basket of Baskets; Cancer Core Europe; adaptive designs; basket protocols; umbrella protocols.

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Conflict of interest statement

EG declares Advisory role for Roche, Janssen, NeoMed Therapeutics, Boehringer and Ellipses Pharma; Speaker's fee from MSD and Direct Research Funding from Novartis. RD declares Advisory role for Roche and Novartis; Speaker's fee from Roche, Symphogen, Ipsen, Amgen and Sanofi and Direct Research Funding from Merck. AP‐G has no conflicts to declare. IB declares Advisory role for Orion Pharma; Speaker's fee from BMS, AstraZeneca and Merck Serono; and Financial Support for clinical trials or contracted research for AstraZeneca, BMS, Celgene, Gliknik, GSK, Janssen, KURA, MSD, Novartis, Orion Pharma and Pfizer. JR declares Advisory role for Novartis, Eli Lilly, Orion Pharmaceuticals, Servier Pharmaceuticals, Peptomyc, Merck Sharp & Dohme, Kelun Pharmaceutical/Klus Pharma, Spectrum Pharmaceuticals Inc, Pfizer, Roche Pharmaceuticals, and Ellipses Pharma; and Direct Research Funding from Bayer and Novartis; and serving as investigator in clinical trials with Spectrum Pharmaceuticals, Tocagen, Symphogen, BioAtla, Pfizer, GenMab, CytomX, Kelun‐Biotech, Takeda‐Millennium, Glaxo Smith Kline and Ipsen. JT declares Advisory role for Array Biopharma, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Genentech, Inc., Genmab A/S, Halozyme, Imugene Limited, Inflection Biosciences Limited, Ipsen, Kura Oncology, Lilly, MSD, Menarini, Merck Serono, Merrimack, Merus, Molecular Partners, Novartis, Peptomyc, Pfizer, Pharmacyclics, ProteoDesign SL, Rafael Pharmaceuticals, F. Hoffmann‐La Roche Ltd, Sanofi, SeaGen, Seattle Genetics, Servier, Symphogen, Taiho, VCN Biosciences, Biocartis, Foundation Medicine, HalioDX SAS and Roche Diagnostics; and Financial Support for clinical trials or contracted research for Agendia BV, Amgen, Debiopharm, Janssen‐Cilag, Mologen AG, Novartis, Pharma Mar, Roche, Servier and Symphogen.

Figures

Figure 1
Figure 1
Design of the BoB platform sponsored by CCE.
See this image and copyright information in PMC

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