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Review
. 2022 Aug 31;14(1):101.
doi: 10.1186/s13073-022-01102-1.

Clinical trial design in the era of precision medicine

Affiliations
Review

Clinical trial design in the era of precision medicine

Elena Fountzilas et al. Genome Med. .

Abstract

Recent rapid biotechnological breakthroughs have led to the identification of complex and unique molecular features that drive malignancies. Precision medicine has exploited next-generation sequencing and matched targeted therapy/immunotherapy deployment to successfully transform the outlook for several fatal cancers. Tumor and liquid biopsy genomic profiling and transcriptomic, immunomic, and proteomic interrogation can now all be leveraged to optimize therapy. Multiple new trial designs, including basket and umbrella trials, master platform trials, and N-of-1 patient-centric studies, are beginning to supplant standard phase I, II, and III protocols, allowing for accelerated drug evaluation and approval and molecular-based individualized treatment. Furthermore, real-world data, as well as exploitation of digital apps and structured observational registries, and the utilization of machine learning and/or artificial intelligence, may further accelerate knowledge acquisition. Overall, clinical trials have evolved, shifting from tumor type-centered to gene-directed and histology-agnostic trials, with innovative adaptive designs and personalized combination treatment strategies tailored to individual biomarker profiles. Some, but not all, novel trials now demonstrate that matched therapy correlates with superior outcomes compared to non-matched therapy across tumor types and in specific cancers. To further improve the precision medicine paradigm, the strategy of matching drugs to patients based on molecular features should be implemented earlier in the disease course, and cancers should have comprehensive multi-omic (genomics, transcriptomics, proteomics, immunomic) tumor profiling. To overcome cancer complexity, moving from drug-centric to patient-centric individualized combination therapy is critical. This review focuses on the design, advantages, limitations, and challenges of a spectrum of clinical trial designs in the era of precision oncology.

Keywords: Clinical trials; Personalized medicine; Precision oncology; Real-world data.

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Conflict of interest statement

Dr. Elena Fountzilas has the following financial relationships to disclose: Travel grants: Merck, Pfizer, and K.A.M Oncology/Hematology; Speaker fees: Roche, Leo, Pfizer; Stock ownership: Deciphera Pharmaceuticals, Inc.

Dr. Apostolia-Maria Tsimberidou has the following financial relationships to disclose: Research Funding (Institution): OBI Pharma, Parker Institute for Cancer Immunotherapy, Immatics, Tvardi Therapeutics, Tempus, Boston Biomedical, Placon Therapeutics, Karus Therapeutics, Agenus and Novocure. Consulting or Advisory Role: Vincerx, Diaccurate.

Dr. Razelle Kurzrock has the following financial relationships to disclose: Research Funding (Institution): Incyte, Genentech, Merck Serono, Pfizer, Sequenom, Foundation Medicine, Konica Minolta, Grifols, Biologic Dynamics, Boehringer Ingelheim, Medimmune, and Guardant. Consulting role: X-Biotech, Loxo, Biologic Dynamics, Turning Point, TD2, Bicara, and Actuate Therapeutics. Speaker fees: Roche. Ownership interest: IDbyDNA and CureMatch, Inc. Board member: CureMatch and CureMetrix.

Dr. Henry Hiep Vo reports no relevant conflicts of interest.

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