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International Journal of Clinical Oncology

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Open Access 19-12-2023 | Targeted Therapy | Original Article

Platform trial for off-label oncology drugs using comprehensive genomic profiling under the universal public healthcare system: the BELIEVE trial

Authors: Sae Ishimaru, Tatsunori Shimoi, Kuniko Sunami, Miho Nakajima, Yayoi Ando, Natsuko Okita, Kenichi Nakamura, Taro Shibata, Yasuhiro Fujiwara, Noboru Yamamoto

Published in: International Journal of Clinical Oncology | Issue 2/2024

Abstract

Background

Precision medicine has transformed cancer treatment by focusing on personalized approaches based on genomic abnormalities. However, comprehensive genomic profiling (CGP) and access to targeted therapies are limited in Japan. This study investigates the BELIEVE trial, which aims to improve drug accessibility for patients with actionable genetic abnormalities through off-label drug administration.

Methods

The BELIEVE trial is a platform trial with a single master protocol, conducted under the Clinical Trials Act and the patient-proposed health services (PPHS) scheme. Eligible patients with solid tumors exhibiting actionable alterations were enrolled, and CGP tests covered by national health insurance were employed. Treatment selection, study drugs from collaborating pharmaceutical companies, and treatment schedules adhered to predefined protocols. Primary and secondary endpoints were evaluated, and statistical analysis was conducted based on patient response rates.

Results

The BELIEVE trial offered treatment opportunities for patients with relapse/refractory disease who lacked standard therapies or clinical trial options. This study addresses unmet medical needs and contributes to the establishment of precision medicine systems. Similar trials like NCI-MATCH and TAPUR are being conducted globally. The BELIEVE trial provides a platform for off-label drug administration, collects essential clinical data, and contributes to drug approval applications.

Conclusion

The BELIEVE trial provides hope for patients with actionable genetic abnormalities by facilitating access to targeted therapies through off-label drug administration. It establishes a regulatory framework and promotes collaboration between industry and academia by expanding organ-specific and cross-organ biomarker-based treatments.

Friedman AA, Letai A, Fisher DE et al (2015) Precision medicine for cancer with next-generation functional diagnostics. Nat Rev Cancer 15:747–756CrossRefPubMedPubMedCentral

Pestana RC, Sen S, Hobbs BP et al (2020) Histology-agnostic drug development—considering issues beyond the tissue. Nat Rev Clin Oncol 17:555–568CrossRefPubMed

Bun S, Yonemori K, Sunadoi H et al (2021) Safety and evidence of off-label use of approved drugs at the National Cancer Center Hospital in Japan. JCO Oncol Pract 17:e416–e425CrossRefPubMed

Nakamura K, Shibata T (2020) Regulatory changes after the enforcement of the new Clinical Trials Act in Japan. Jpn J Clin Oncol 50:399–404CrossRefPubMedPubMedCentral

Ueda K, Sanada S, Uemura N (2020) Advanced medical care program for the rapid introduction of healthcare technologies to the national health insurance system in Japan. Clin Transl Sci 13:700–706CrossRefPubMedPubMedCentral

Ministry of Health, Labour and Welfare. Overview of each technology to be implemented under the Advanced Medical Care system. https://www.mhlw.go.jp/topics/bukyoku/isei/sensiniryo/kikan03.html

Ministry of Health, Labour and Welfare. Overview of each technology for Patient-Proposed Health Services. https://www.mhlw.go.jp/topics/bukyoku/isei/kanja/kikan03.html

Sunami K, Ichikawa H, Kubo T et al (2019) Feasibility and utility of a panel testing for 114 cancer-associated genes in a clinical setting: a hospital-based study. Cancer Sci 110:1480–1490CrossRefPubMedPubMedCentral

Zehir A, Benayed R, Shah RH et al (2017) Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med 23:703–713CrossRefPubMedPubMedCentral

10.

Dienstmann R, Jang IS, Bot B et al (2015) Database of genomic biomarkers for cancer drugs and clinical targetability in solid tumors. Cancer Discov 5:118–123CrossRefPubMedPubMedCentral

11.

Debien V, Vignot S, Massard C et al (2013) Molecular analysis for refractory rare cancers: sequencing battle continues—learnings for the MOSCATO-01 study. Crit Rev Oncol Hematol 181:103888CrossRef

12.

Trédan O, Wang Q, Pissaloux D et al (2019) Molecular screening program to select molecular-based recommended therapies for metastatic cancer patients: analysis from the ProfiLER trial. Ann Oncol 30:757–765CrossRefPubMed

13.

Fujiwara Y (2016) Evolution of frameworks for expediting access to new drugs in Japan. Nat Rev Drug Discov 15:293–294CrossRefPubMed

14.

Mukai Y, Ueno H (2021) Establishment and implementation of cancer genomic medicine in Japan. Cancer Sci 112:970–977CrossRefPubMedPubMedCentral

15.

List of the designated core hospitals for cancer genomic medicine in the system for providing cancer genomic medicine. https://www.mhlw.go.jp/content/000928433.pdf

16.

Japan Registry of Clinical Trials. https://jrct.niph.go.jp/latest-detail/jRCTs031190104

17.

Kohno T, Kato M, Kohsaka S et al (2022) C-CAT: the national datacenter for cancer genomic medicine in Japan. Cancer Discov 12:2509–2515CrossRefPubMedPubMedCentral

18.

Sunami K, Takahashi H, Tsuchihara K et al (2018) Clinical practice guidance for next-generation sequencing in cancer diagnosis and treatment (Edition 1.0). Cancer Sci 109:2980–2985CrossRefPubMedPubMedCentral

19.

Japanese Society of Medical Oncology, Japan Society of Clinical Oncology, and Japanese Cancer association. The guidance for cancer treatment based on gene panel testing using next-generation sequencers (2.1 edition) http://www.jca.gr.jp/researcher/topics/2020/files/20200518.pdf

20.

Li MM, Datto M, Duncavage EJ et al (2017) Standards and guidelines for the interpretation and reporting of sequence variants in cancer: a joint consensus recommendation of the association for molecular pathology, American Society of Clinical Oncology, and College of American Pathologists. J Mol Diagn 19:4–23CrossRefPubMedPubMedCentral

21.

Mateo J, Chakravarty D, Dienstmann R et al (2018) A framework to rank genomic alterations as targets for cancer precision medicine: the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT). Ann Oncol 29:1895–1902CrossRefPubMedPubMedCentral

22.

Ministry of Health, Labour and Welfare. Report of the fact survey of gene panel tests. https://www.mhlw.go.jp/content/10901000/000573712.pdf

23.

Sunami K, Naito Y, Aimono E et al (2021) The initial assessment of molecular tumor board performance in core hospitals for cancer genomic medicine in Japan. Int J Clin Oncol 26:443–449CrossRefPubMedPubMedCentral

24.

Lewis JR, Kerridge I, Lipworth W (2015) Coverage with evidence development and managed entry in the funding of personalized medicine: practical and ethical challenges for oncology. J Clin Oncol 33:4112–4117CrossRefPubMed

25.

Mangat PK, Halabi S, Bruinooge SS et al (2018) Rationale and design of the targeted agent and profiling utilization registry (TAPUR) study. JCO Precis Oncol 2:1–4CrossRef

26.

Flaherty KT, Gray R, Chen A et al (2020) The molecular analysis for therapy choice (NCI-MATCH) trial: lessons for genomic trial design. J Natl Cancer Inst 112:1021–1029CrossRefPubMedPubMedCentral

27.

Robinson JC (2022) Drug pricing with evidence development. JAMA 327:1545–1546CrossRefPubMed

28.

Allen CE, Laetsch TW, Mody R et al (2017) Target and agent prioritization for the Children’s Oncology Group-National Cancer Institute Pediatric MATCH trial. J Natl Cancer Inst 109:djw274CrossRefPubMedPubMedCentral

29.

Parsons DW, Janeway KA, Patton DR et al (2022) Actionable tumor alterations and treatment protocol enrollment of pediatric and young adult patients with refractory cancers in the National Cancer Institute-Children’s Oncology Group Pediatric MATCH trial. J Clin Oncol 40:2224–2234CrossRefPubMedPubMedCentral

Title: Platform trial for off-label oncology drugs using comprehensive genomic profiling under the universal public healthcare system: the BELIEVE trial
Authors: Sae Ishimaru
Tatsunori Shimoi
Kuniko Sunami
Miho Nakajima
Yayoi Ando
Natsuko Okita
Kenichi Nakamura
Taro Shibata
Yasuhiro Fujiwara
Noboru Yamamoto
Publication date: 19-12-2023
Publisher: Springer Nature Singapore
Keyword: Targeted Therapy
Published in: International Journal of Clinical Oncology / Issue 2/2024
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-023-02439-2

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Abstract

Background

Methods

Results

Conclusion

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