1711P - The DRUP-like clinical trials family: A distributed European trial network for equitable access to precision medicine

Background

While the promise of personalised cancer medicine (PCM) is clear, implementation remains challenging. In the European Union (EU), healthcare systems fall under national responsibility and differ greatly in structure, financing and capacity. Furthermore, EU countries are predominantly small, limiting generated evidence from national trials. The family of DRUP-like clinical trials (DLCTs) addresses this challenge: as a bottom–up, clinician-initiated initiative, DLCTs share the pragmatic core clinical trial design of the original Drug Rediscovery Protocol (DRUP), anchored into national context and financed independently. The result is a distributed DLCT network that addresses local priorities while collaborating internationally for scale and impact.

Methods

In 2022, the DLCT community successfully applied for two projects funded by the EU that will expand the network by supporting investigators to establish national DLCTs in additional countries. At the same time, the projects will build shared cross-DLCT capacity in molecular diagnostics and education (PCM4EU) as well as cross-trial data analytics, initiate shared cohorts and provide Health Technology Assessments (HTA) (based on the EUnetHTA core model) and Health Economic Evaluations (PRIME-ROSE). To ensure successful implementation, the projects involve various national and European decision-makers as well as the cancer patient community.

Results

Our approach demonstrates the feasibility of a novel type of pragmatic clinical trial networks that rely on distributed rather than centralized leadership. This way ensures wide and equitable patient inclusion and building national capacity in PCM diagnostics and treatments. Further, the set-up of a shared core, but variable side modules, allows for parallel experimentation and fast implementation of successful findings by adding these to the common DRUP core model.

Conclusions

This Europe-wide PCM deployment will address key scientific and methodological questions to accelerate broad and equitable access to new and effective cancer treatments. The ongoing effort is leading to standardization and pragmatic consensus, thereby anticipating the benefits of the upcoming European Health Data Space.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

European Commission (EU) EU4Health / Europe Beating Cancer Programme, EC grant agreement no. 101079984 (PCM4EU) and Horizon Europe Cancer Mission, EC grant agreement no. 101104269 (PRIME-ROSE).

Disclosure

H. Gelderblom: Financial Interests, Institutional, Local PI: Daiichi Sankyo, Deciphera, Novartis, Cytovation; Financial Interests, Institutional, Coordinating PI: Boehringer Ingelheim, AmMax Bio, Debiopharm. H.E.G. Russnes: Financial Interests, Institutional, Invited Speaker, Speaker on Illumina satellite meeting (ESMO 2022): Illumina; Financial Interests, Institutional, Advisory Board, Novartis satellite meeting, Nordic Lung Cancer meeting, 2022: Novartis; Financial Interests, Institutional, Other, Debate, precision medicine, Oslo 2022 : Merck; Financial Interests, Institutional, Other, Participation, round table, Cholangiocarcinoma; Nordic meeting 2021: Incyte; Financial Interests, Institutional, Coordinating PI, Funding of 500 FMliquid test to patients in the IMPRESS-Norway trial: Roche Norway; Financial Interests, Institutional, Coordinating PI, Funding of TSO500 liquid tests for 500 patients in the IMPRESS-Norway trial: Illumina; Non-Financial Interests, Leadership Role, InPreD is an establishment in the public health care, securing disciplinary work when implementing precision diagnostics for cancer.: National Infrastructure for Precision Diagnostics (InPreD); Non-Financial Interests, Leadership Role, A network structure established as part of the public health care system, to share knowledge, build competence and work with harmonisation and standardisation to implement precision medicine.: National Competence Network for Precision Medicine; Non-Financial Interests, Leadership Role, Head of working group for molecular pathology and for the Norwegian association for molecular pathology: The Norwegian Association of Pathology. U.N. Lassen: Financial Interests, Personal, Advisory Board: Bayer, Novartis; Financial Interests, Institutional, Research Grant: Roche, BMS, Pfizer, GSK, Lilly, Incyte. A. Helland: Financial Interests, Institutional, Advisory Board, Advisory boards: Jansen, Takeda, AstraZeneca, AbbVie, Roche, BMS, Pfizer, MSD, Bayer, Lilly,; Financial Interests, Institutional, Invited Speaker, talks at meetings: AstraZeneca, Roche, AbbVie, Pfizer; Financial Interests, Institutional, Coordinating PI, BMS provides drug to patients in an investigator initiated clinical trial: BMS; Financial Interests, Institutional, Coordinating PI, Ultimovacs provides drug and funds for investigator initiated clinical trial: Ultimovacs; Financial Interests, Institutional, Coordinating PI, AstraZeneca provides drug and funds for investigator initiated clinical trial: AstraZeneca; Financial Interests, Institutional, Coordinating PI, Roche provides drug and funds for investigator initiated clinical trial: Roche; Financial Interests, Institutional, Coordinating PI, Novartis provides drug and funds for clinical trial: Novartis; Financial Interests, Institutional, Coordinating PI, Eli Lilly provides drug and funds for clinical study: Eli Lilly; Financial Interests, Institutional, Coordinating PI, Incyte provides drug and funds for clinical study: Incyte; Financial Interests, Institutional, Coordinating PI, Illumina provides assays for patients in a clinical trial: Illumina; Non-Financial Interests, Other, Board member in the patient organisation until 2022. Provides advice and gives talks.: The lung cancer patients organisation. B. Ryll: Non-Financial Interests, Personal, Advisory Board: Clinigen Healthcare, Roche, Pierre Fabre; Other, Personal and Institutional, Advisory Board: MSD Oncology, BMS GmbH & Co. KG, Novartis. I. Lugowska: Financial Interests, Personal, Writing Engagement: Roche, ESMO; Financial Interests, Institutional, Other, Research grants: ROCHE; Financial Interests, Institutional, Other, Research grant: Agenus; Financial Interests, Personal and Institutional, Coordinating PI: MSD, Roche, BMS, Janssen, Astra, Amgen, RyVu, Incyte, Siropa, Menarini, Celon, Pfizer, Agenus, Rhizen; Non-Financial Interests, Project Lead: MSCI; Non-Financial Interests, Other, Board Member: OECI; Other, Other, Robert Lugowski (my husband) co-ownership: Clininote. J. Blay: Financial Interests, Personal, Advisory Board: Bayer, Deciphera, GSK, Roche; Financial Interests, Personal, Invited Speaker: PharmaMar; Financial Interests, Institutional, Invited Speaker: MSD, MSD; Financial Interests, Personal, Other, member of the supervisory board: Innate pharma; Financial Interests, Institutional, Funding: MSD, BMS, Deciphera; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Bayer, GSK, Novartis, OSE pharma. K. Peltola: Other, Personal, Other, Employment of an immediate family member: Terveystalo; Non-Financial Interests, Personal, Advisory Role: MSD Oncology, Lilly, Pfizer, Bristol Myers Squibb, Novartis, Ipsen, Roche; Financial Interests, Personal, Stocks or ownership: Faron Pharmaceuticals; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Bristol Myers Squibb, Roche; Financial Interests, Personal, Research Funding: Novartis, Roche, Bayer, Lilly. A. Stenzinger: Financial Interests, Personal, Advisory Board: Aignostics, AstraZeneca, Janssen, Bayer, Seattle Genetics, Pfizer, MSD, Eli Lilly, Illumina, Thermo Fisher, Amgen; Financial Interests, Institutional, Advisory Board: BMS, Takeda, Novartis; Financial Interests, Personal, Invited Speaker: Roche, Incyte; Financial Interests, Institutional, Research Grant: Bayer, Chugai, BMS, Incyte. J. Oliveira: Financial Interests, Personal, Other, Advisory board, Invited speaker: AstraZeneca, Roche, Novartis, Janssen; Financial Interests, Personal, Invited Speaker: GSK, BMS, MSD, Bayer; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Institutional, Funding, Investigator Initiated Clinical Trial funding: AstraZeneca. H.M.W. Verheul: Non-Financial Interests, Institutional, Advisory Role: Lava Therapeutics, Philips Healthcare. E.E. Voest: Financial Interests, Personal, Advisory Board, Hourly rate, to charity: Biogeneration Ventures; Financial Interests, Institutional, Advisory Board, Hourly rate, no compensation in 2019-2020: InteRNA; Financial Interests, Personal, Member of Board of Directors, independent, non-executive director and share holder: Sanofi; Financial Interests, Personal, Other, Founder, strategic adviser and share holder: Mosaic Therapeutics; Financial Interests, Personal, Ownership Interest, Mandatory shares as part of board membership: Sanofi; Financial Interests, Personal, Ownership Interest, Start-up company with shares: Mosaic Therapeutics; Financial Interests, Institutional, Coordinating PI, DRUP trial: Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Clovis Oncology, Eisai, Ipsen, MSD, Novartis, Pfizer, GSK, Seattle Genetics; Financial Interests, Institutional, Coordinating PI, DRUP trialDrug Access Protocol: Bayer, Roche; Financial Interests, Institutional, Coordinating PI, Drug Access Protocol: Sanofi; Non-Financial Interests, Other, Supervisory Board: HMF – Hartwig Medical Foundation; Non-Financial Interests, Principal Investigator, Senior group leader: Oncode Institute; Non-Financial Interests, Advisory Role, Editorial Board: JAMA Oncology; Non-Financial Interests, Leadership Role, Board of Directors: Cancer Core Europe. K. Tasken: Non-Financial Interests, Personal, Advisory Role: Serca Pharmaceuticals; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche; Financial Interests, Personal, Stocks or ownership: Serca Pharmaceuticals, Ledidi; Financial Interests, Personal, Other, Stock and Stock options, and royalty agreement: Oslo University Hospital / University of Oslo Tech Transfer Office Inven2 AS; Financial Interests, Institutional, Research Funding: Roche, Novartis, Lilly, Incyte, Merck KGaA, AstraZeneca, Illumina. All other authors have declared no conflicts of interest.