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 high-light how insights from already-ongoing studies may address current challenges and opportunities in the era of personalised oncology.(c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Automated summary

Personalised oncology is becoming an essential part of clinical care, guided by molecular tumour profiles and next-generation sequencing technology. Clinical trials have shifted towards biomarker-driven studies of molecularly guided therapies and cancer immunotherapies, requiring a multistakeholder perspective. Innovative technologies and dynamic design methodologies will be necessary for efficient translation of scientific discoveries into clinical utility in the future of cancer clinical trials.