1235P - Enrichment of rare cancers in pragmatic precision cancer medicine trial: Experience from IMPRESS-Norway

Background

IMPRESS-Norway is a DRUP-like, national clinical study for patients with advanced malignancies, where approved drugs are used outside their indication based on detailed molecular diagnostics. All hospitals in Norway treating cancer patients participate. Rare cancers comprise a group of about 200 cancers that individually occur at low to very low frequencies. For these cancers, randomized trials are difficult to conduct, and they have few approved therapeutic options. Clinical studies are therefore needed.

Methods

In IMPRESS-Norway, patients are screened with TSO500, analysing 535 genes for DNA/RNA alterations. Both tumour tissue and circulating tumour DNA are analysed. We currently have 23 drugs available through the study and can use these outside of their indications, based on identified molecular alterations in the tumour cells in an aggregated treatment algorithm and subject to discussion in a national molecular tumour board.

Results

In the first 2 years, 836 patients were included for screening in IMPRESS-Norway. Of these, 411 patients have a rare cancer diagnosis. 83 patients with a rare cancer (20.2%) were offered treatment based on the molecular diagnostics, whereas 97 of 425 screened with a common cancer (22.8%) were included in treatment cohorts. The most common drugs offered patients with rare cancers were trametinib, alpelisib and atezolizumab. The primary endpoint in the study is clinical benefit at 16 weeks of treatment, which was observed for 53% of patients with rare cancers compared to 42% for patients with common cancers.

Conclusions

In our ongoing study, 49.2% of the patients included for screening in the first 2 years had a rare cancer, and actionable molecular alterations matching one of the drugs available in the trial were found for 20.2% of the patients. We show that many of these patients benefit from advanced diagnostics and from drugs used outside of their current indication. This finding is of special importance for patient groups for whom access to clinical trials are limited due to the rareness of the disease.

Clinical trial identification

NCT04817956.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

The Regional Health Authorities, The Norwegian Cancer Society, The Radium Hospital Foundation , Pharma companies providing drug and funds for treating hospital: AstraZeneca, Roche, InCyte, Novartis, Merck, Eli Lilly.

Disclosure

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. G.O. Hjortland: Financial Interests, Institutional, Research Grant: Astra, Merck, Illumina Roche, Novartis, EliLilly, InCyte. L. Bjorge: Financial Interests, Personal, Advisory Board, Expert testimony regarding a patent application: Onsagers, Oslo; Financial Interests, Personal, Advisory Board, Expert testimony for an application to The National System for Managed Introduction of New Health Technologies within the Specialist Health Service in Norway: AstraZeneca; Financial Interests, Personal, Advisory Board, Part of an ad hoc advisory board for ovarian cancer: AstraZeneca; Financial Interests, Personal, Member of Board of Directors, Oslo Cancer Cluster is an oncology research and industry cluster dedicated to improving the lives of cancer patients by accelerating the development of new cancer diagnostics and treatment. Been part of the board during the period 2015-2022 (elected): Oslo Cancer Cluster; Financial Interests, Personal, Full or part-time Employment, I hold a full-time position as Medical Director and consultant in gynecologic oncology at this institution: Helse Bergen HF; Financial Interests, Personal, Full or part-time Employment, I hold a part-time position as Professor in Obstetrics and Gynecology: University of Bergen; Financial Interests, Institutional, Research Grant, Financial support for a researcher-initiated trial: AstraZeneca; Non-Financial Interests, Leadership Role, Onkologisk Forum is the interest organization for all groups of personal working with cancer patients or cancer treatment or cancer research in Norway, https://onkologiskforum.org/om-onkologisk-forum. During the period 2018-2022 I been the leader for the organization (elected position): Onkologisk Forum; Non-Financial Interests, Leadership Role, From March 2021 hold the position as president for the organization: Nordic Society for Gynecological Oncology; Non-Financial Interests, Leadership Role, Leader of the board since March 2021: Nordic Society of Gynecologic Oncology-Clinical Trial Unit; Non-Financial Interests, Advisory Role, Member of the specialist group in oncology, Sykehusinnkjøp HF, Representing Helse Vest RHF: Sykehus Innkjøp HF; Non-Financial Interests, Leadership Role, Since March 2021 I have hold the position as president for the organization. I have been a member of the organization since 2012, and a board member since 2014: Nordic Society of Gynecologic Oncology; Non-Financial Interests, Member, I have been a member since 2011: ESGO; Non-Financial Interests, Member, I have been a member since 2015: ASCO; Other, I have been evaluating grant applications from different national and international research institutions and grant providers: Different academic institutions. B. Gilje: Financial Interests, Personal, Advisory Board, June 2022 Ad Board: Gilead; Financial Interests, Personal, Advisory Board: Eli Lilly, Daiichi Sankyo, Pierre Fabre, Roche. T. Donnem, O.T.D. Nguyen, B. Mannsåker, S. Smeland, K. Tasken: Financial Interests, Institutional, Research Grant: Astra, Merck, Illumina Roche, Novartis, Eli Lilly, InCyte. A. Flobak: Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Pfizer, Pierre Fabre, Amgen, Bayer. 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. T.K.K. Guren: Financial Interests, Institutional, Other, Honoraria: Pierre Fabre; Financial Interests, Institutional, Local PI: Genentech/Roche, MSD, Merus, Pfizer, Ultimovacs, Eli Lilly/Loxo, Novartis, Boehringer Ingelheim. All other authors have declared no conflicts of interest.