197P - PRIME-ROSE: Merging clinical outcome data from DRUP-like clinical trials

Background

PRIME-ROSE is a European Cancer Mission project on precision cancer medicine trials. It currently encompasses 11 ongoing or soon-to-start DRUP-like clinical trials in various countries (www.prime-rose.eu). These trials are exploring the effect of biomarker-driven treatments outside their current label in a broad variety of tumor types. Such testing in cancer subtypes requires the ability to find patients with rare biomarkers or tumors to offer treatment with matched drugs available in each trial’s drug portfolio. In PRIME-ROSE, the ongoing trials share and aggregate data on patients with the same tumor type, biomarker and drug combination. This collaborative effort will significantly improve the recruitment rate of each cohort, enabling more rapid evidence-building, which directly impacts patient care. The trial network currently has a recruitment area of 71 million inhabitants. Here, we report the first PRIME-ROSE data aggregation.

Methods

After aligning biomarker and tumor definitions, data on patients with advanced or metastatic cancer who harbored actionable alterations and received matched drugs were merged for analysis. The analysis included adult patients who had standard therapy-refractory solid malignancies. Cohorts with 8 patients (stage I) after merging were analyzed for clinical benefit (CB), defined as confirmed objective response or stable disease ≥16 weeks. If one or more of the 8 patients had CB at week 16 of treatment, the cohort moved to stage II and expanded with an additional 16 patients. Data have been merged from FINPROVE in Finland, ProTarget in Denmark, IMPRESS-Norway in Norway, and DRUP in the Netherlands.

Results

The trials are aligned with respect to protocol and end-points, enabling effective merging of cohorts. However, alignment on biomarker definition and tumor type for each cohort is necessary. A total of 7 cohorts are currently in process of merging between DRUP, ProTarget, IMPRESS-Norway, and FINPROVE, of which 5 have included 8 or more patients in total, allowing for analysis of clinical outcome and decision on moving these cohorts to stage II (24 patients).

Conclusions

Merging of data between the DRUP-like clinical trials is feasible and will increase the inclusion rate in cohorts considerably.

Clinical trial identification

DRUP - NCT02925234 FINPROVE - NCT05159245 ProTarget - NCT04341181 IMPRESS-Norway - NCT04817956 MegaMost - NCT04116541 Most plus - NCT02029001 DETERMINE - NCT05722886.

Editorial acknowledgement

Legal entity responsible for the study

Oslo University Hospital.

Funding

European Commission's Mission on Cancer programme.

Disclosure

L. Verlingue: Financial Interests, Personal, Stocks/Shares, CEO of Resolved dedicated to treatment approval prediction: Resolved; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Funding, Contract for bioinformatic analysis: Pierre Fabre, Servier; Non-Financial Interests, Advisory Role: Klineo; Non-Financial Interests, Institutional, Proprietary Information, As part of the Drug Development Department (DITEP) of Gustave Roussy and of the Phase 1 unit of Centre Léon Bérard, as medical doctor, LV report being: Principal/sub-Investigator of Clinical Trials for AbbVie, Adaptimmune, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca Ab, Aveo, Basilea Pharmaceutica International Ltd, Bayer Healthcare Ag, Bbb Technologies Bv, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Ca, Celgene Corporation, Chugai Pharmaceutical Co, Clovis Oncology, Cullinan-Apollo, Daiichi Sankyo, Debiopharm, Eisai, Eisai Limited, Eli Lilly, Exelixis, Faron Pharmaceuticals Ltd, Forma Tharapeutics, Gamamabs, Genentech, GSK, H3 Biomedicine, Hoffmann-La Roche Ag, Imcheck Therapeutics, Innate Pharma, Institut De Recherche Pierre Fabre, Iris Servier, Janssen Cilag, Janssen Research Foundation, Kura Oncology, Kyowa Kirin Pharm. Dev, Lilly France, Loxo Oncology, Lytix Biopharma A: Pharmas. M.G. Krebs: Financial Interests, Personal, Advisory Board: Bayer, Roche, Janssen, Guardant Health, Zai Lab; Financial Interests, Personal, Invited Speaker: Roche, Janssen; Financial Interests, Institutional, Advisory Board: AstraZeneca, Seattle Genetics; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Carrick, Janssen, Pyramid Biosciences, Ellipses; Financial Interests, Institutional, Local PI: Blueprint, Astex, Bayer, BerGenBio, Immutep, Novartis, Nurix, Nuvalent, Roche, Seattle Genetics, Turning Point Therapeutics, Relay Therapeutics; Financial Interests, Institutional, Research Grant: Roche, Novartis; Other, Travel expenses for congress: Immutep, Janssen; Other, Travel expenses: Roche, Zai Lab. J. Blay: Financial Interests, Institutional, Invited Speaker: MSD, MSD, PharmaMar; Financial Interests, Institutional, Advisory Board: Bayer, GSK, Roche; Financial Interests, Personal, Advisory Board: Deciphera; Financial Interests, Personal, Other, member of the supervisory board. No remunerations in 2021 and 2022.: Innate pharma; Financial Interests, Personal, Member of Board of Directors: Transgene; Financial Interests, Institutional, Funding: MSD, BMS, Deciphera; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Bayer, GSK, Novartis, OSE pharma. K. Jalkanen: Financial Interests, Personal, Advisory Board: MSD, Ipsen, Roche, BMS, Pfizer, Lilly, Novartis, Bayer; Financial Interests, Personal, Stocks/Shares: Faron Pharmaceuticals; Financial Interests, Institutional, Local PI, Conduct of sponsored clinical trial: Novartis; Financial Interests, Institutional, Local PI, Sponsored clinical trial: Exelixis; Financial Interests, Institutional, Local PI, Several clinical trials: BMS, MSD, Roche; Financial Interests, Institutional, Local PI, clinical trials: Incyte; Financial Interests, Institutional, Local PI, Conduct of clinical trials: Pfizer; Financial Interests, Institutional, Local PI, Conduct of clinical trial: Bayer. K.S. Rohrberg: Financial Interests, Personal, Invited Speaker: Bayer, Amgen, MSD, GSK; Financial Interests, Personal, Advisory Board: AbbVie, Genmab; Financial Interests, Institutional, Coordinating PI, Compensation for conduction of clinical trial.: Lilly, Roche/Genentech, Bristol Myers Squibb, Symphogen, Pfizer, Novartis, Alligator Bioscience, Genmab, Bioinvent, Monta Bioscience, Navire; Financial Interests, Institutional, Other, Compensation for conduction of clinical trial.: Bayer, Incyte, Puma Biotechnology, Orion Clinical; Financial Interests, Institutional, Local PI, Compensation for conduction of clinical trial.: Amgen. U.N. Lassen: Financial Interests, Personal, Advisory Board: Bayer, Novartis; Financial Interests, Institutional, Research Grant: Roche, BMS, Pfizer, GSK, Lilly, Incyte, Janssen. A. Helland: Financial Interests, Institutional, Advisory Board, Advisory boards: Jansen, Takeda, AstraZeneca, AbbVie, Roche, BMS, Pfizer, MSD, Bayer, Lilly, Medicover; 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; Financial Interests, Institutional, Coordinating PI, GSK provides drug and funds for investigator initiated clinical trial: GSK; Non-Financial Interests, Other, Board member in the patient organisation until 2022. Provides advice and gives talks.: The lung cancer patients organisation. E.E. Voest: Financial Interests, Personal, Advisory Board, Hourly rate: Biogeneration Ventures; 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, BMS, 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. H. Gelderblom: Financial Interests, Institutional, Local PI: Deciphera, Cytovation; Financial Interests, Institutional, Coordinating PI: Boehringer Ingelheim, AmMax Bio, Debiopharm, Abbisko. K. Tasken: Financial Interests, Personal, Advisory Board, Company established based on innovation in my lab. Holds stock and Scientific advisor: Serca Pharmaceuticals; Financial Interests, Personal, Stocks/Shares, Stock and Stock options, and royalty agreement through Oslo UniversityHospital/University of Oslo Tech Transfer Office Inven2 AS.: Serca Pharmaceuticals; Financial Interests, Personal, Stocks/Shares, Stock.: Ledidi; Financial Interests, Personal, Royalties, Stock and Stock options, and royalty agreement through Oslo UniversityHospital/University of Oslo Tech Transfer Office Inven2 AS.: Serca Pharmaceuticals; Financial Interests, Institutional, Steering Committee Member, IMPRESS-Norway trial Trial Management & Steering Committee: Roche; Financial Interests, Institutional, Steering Committee Member, IMPRESS Norway trial Trial Management & Steering Committee: Novartis, Lilly, Incyte, Merck KGaA, AstraZeneca, Illumina. All other authors have declared no conflicts of interest.