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. 2024 Oct;56(4):991-1013.
doi: 10.4143/crt.2024.128. Epub 2024 May 7.

Precision Oncology Clinical Trials: A Systematic Review of Phase II Clinical Trials with Biomarker-Driven, Adaptive Design

Hyerim Ha  1 , Hee Yeon Lee  2 , Jee Hyun Kim  3 , Do Yeun Kim  4 , Ho Jung An  5 , SeungJin Bae  6 , Hye-Sung Park  7 , Jin Hyoung Kang  7
Affiliations

Precision Oncology Clinical Trials: A Systematic Review of Phase II Clinical Trials with Biomarker-Driven, Adaptive Design

Hyerim Ha et al. Cancer Res Treat. 2024 Oct.

Abstract

Novel clinical trial designs are conducted in the precision medicine era. This study aimed to evaluate biomarker-driven, adaptive phase II trials in precision oncology, focusing on infrastructure, efficacy, and safety. We systematically reviewed and analyzed the target studies. EMBASE and PubMed searches from 2015 to 2023 generated 29 eligible trials. Data extraction included infrastructure, biomarker screening methodologies, efficacy, and safety profiles. Government agencies, cancer hospitals, and academic societies with accumulated experiences led investigator-initiated precision oncology clinical trials (IIPOCTs), which later guided sponsor-initiated precision oncology clinical trials (SIPOCTs). Most SIPOCTs were international studies with basket design. IIPOCTs primarily used the central laboratory for biomarker screening, but SIPOCTs used both central and local laboratories. Most of the studies adapted next-generation sequencing and/or immunohistochemistry for biomarker screening. Fifteen studies included an independent central review committee for outcome investigation. Efficacy assessments predominantly featured objective response rate as the primary endpoint, with varying results. Nine eligible studies contributed to the United States Food and Drug Administration's marketing authorization. Safety monitoring was rigorous, but reporting formats lacked uniformity. Health-related quality of life and patient-reported outcomes were described in some protocols but rarely reported. Our results reveal that precision oncology trials with adaptive design rapidly and efficiently evaluate anticancer drugs' efficacy and safety, particularly in specified biomarker-driven cohorts. The evolution from IIPOCT to SIPOCT has facilitated fast regulatory approval, providing valuable insights into the precision oncology landscape.

Keywords: Adaptive design; Biomarkers; Efficacy; Independent central review committees; Neoplasms; Precision medicine; Safety.

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Conflict of interest statement

Conflict of Interest

Conflict of interest relevant to this article was not reported.

Figures

Fig. 1.
Fig. 1.
The PRISMA diagram for systematic review of precision oncology clinical trials.
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