Modified study designs to expand treatment options in personalised oncology: a multistakeholder view.

Personalised oncology, whereby patients are given therapies based on their molecular tumour profile, is rapidly becoming an essential part of optimal clinical care, at least partly facilitated by recent advances in next-generation sequencing-based technology using liquid- and tissue-based biopsies. Consequently, clinical trials have shifted in approach, from traditional studies evaluating cytotoxic chemotherapy in largely histology-based populations to modified, biomarker-driven studies (e.g. basket, umbrella, platform) of molecularly guided therapies and cancer immunotherapies in selected patient subsets. Such modified study designs may assess, within the same trial structure, multiple cancer types and treatments, and should incorporate a multistakeholder perspective. This is key to generating complementary, fit-for-purpose and timely evidence for molecularly guided therapies that can be used as proof-of-concept to inform further study designs, lead to approval by regulatory authorities and be used as confirmation of clinical benefit for health technology assessment bodies. In general, the future of cancer clinical trials requires a framework for the application of innovative technologies and dynamic design methodologies, in order to efficiently transform scientific discoveries into clinical utility. Next-generation, modified studies that involve the joint efforts of all key stakeholders will offer individualised strategies that ultimately contribute to globalised knowledge and collective learning. In this review, we outline the background and purpose of such modified study designs and detail key aspects from a multistakeholder perspective. We also provide methodological considerations for designing the studies and highlight how insights from already-ongoing studies may address current challenges and opportunities in the era of personalised oncology.

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Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

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Declaration of Competing Interests The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests: Christophe Le Tourneau has received honoraria from Novartis, Bristol Myers Squibb, MSD, Merck Serono, F. Hoffmann-La Roche Ltd, Nanobiotix, GlaxoSmithKline, Celgene, Rakuten Medical and Seattle Genetics; has had a consulting/advisory role for Amgen, MSD, Bristol Myers Squibb, Merck Serono, AstraZeneca, Nanobiotix, GlaxoSmithKline, Celgene, Rakuten, Seattle Genetics and F. Hoffmann-La Roche Ltd; has received research funding from MSD; and has received travel/accommodation expenses from MSD, Bristol Myers Squibb and AstraZeneca. Fabrice André has received institutional research funding from F. Hoffmann-La Roche, Pfizer, Eli Lilly, Novartis, AstraZeneca and Daiichi Sankyo. Åslaug Helland has received honoraria to her institution for talks and advice given to AstraZeneca, Roche, Janssen, Bayer, Novartis, Takeda, Pfizer, Eli Lilly, MSD, BMS, Eli Lilly, AbbVie, Merck and Sanofi; and has received research funding from Roche, AstraZeneca, BMS, Ultimovacs, Incyte, Eli Lilly and Novartis. Linda Mileshkin has received travel/accommodation expenses from F. Hoffmann-La Roche Ltd and BeiGene. Warnyta Minnaard is the cofounder, director and volunteer at Missie Tumor Onbekend, the CUP patient charity in the Netherlands; is also employed by Noaber Ventures; has received honoraria for various presentations at Dutch hospitals in regards to CUP and various presentations to healthcare industry companies (including pharma) on the CUP patient charity to her institution; has received meeting/travel support from F. Hoffmann-La Roche Ltd; and is a volunteer for Stichting Cancer of Unknown Primary Platform—the Netherlands (CUPP-NL). Anja Schiel is an employee of the Norwegian Medicines Agency and acted as Vice-Chair on the EUnetHTA 21 Committee for Scientific Consistency and Quality Joint Scientific Consultations. Kjetil Taskén has received honoraria to his institution for talks and advice given to Roche, Novartis, AbbVie, AstraZeneca, Bayer and Kite/Gilead. David M. Thomas is supported by an NHMRC Investigator grant (GNT1195742), as well as grants, personal fees and non-financial support from F. Hoffmann-La Roche, Pfizer and Bayer; grants and non-financial support from AstraZeneca, Seattle Genetics, Amgen, Eli Lilly and Eisai; personal fees from Omico; and non-financial support from Elevation Oncology, outside the submitted work. Maria Luisa Veronese is an employee of Incyte International Biosciences Sàrl. Gonzalo Durán-Pacheco, Lada Leyens, Kaspar Rufibach and Marlene Thomas are employees of and hold stock/shares in F. Hoffmann-La Roche Ltd. Alwin Krämer has received honoraria from F. Hoffmann-La Roche Ltd, Daiichi Sankyo and AbbVie; has received honoraria to his institution from F. Hoffmann-La Roche Ltd and Bayer; has a leadership role in F. Hoffmann-La Roche Ltd; has received institutional research funding from Merck and Bayer; has received travel/accommodation expenses from F. Hoffmann-La Roche Ltd, Celgene and Daiichi Sankyo; and has acted as an advisory consultant for Daiichi Sankyo, BMS and AbbVie. All authors received research support (medical writing support) from F. Hoffmann-La Roche Ltd.