Abstract 82P
Background
The emergence of molecular tumor profiling has unlocked unprecedented opportunities, facilitating the identification of actionable driver mutations spanning diverse tumor types. FINPROVE (NCT05159245) is an investigator initiated, non-randomized multi-center phase II clinical trial investigating the efficacy of molecularly targeted therapeutics in patients who have exhausted the standard of care therapeutic options. A deeper understanding on the molecular underpinnings of the tumors is urgently needed to enhance precision oncology approaches.
Methods
All patients undergo targeted NGS panel for potentially actionable molecular alterations. We employ advanced bioinformatic analyses on the molecular data, including mutational signature analysis, Nanostring gene-expression profiling, and single-cell spatial proteomics to reveal dysregulated pathways associated with distinct molecular alterations.
Results
Between 1/2022 and 3/2024 we profiled 454 tumors. Of these, 72 (16%) were patients with advanced gynecological malignancies, with an average age of 56 (range 30-76) years. The most common subtype was ovarian cancer (n=41, 57%), followed by uterine (n=13, 25%), cervical, vaginal and vulvar cancers (n=11, 15%). Overall, we observed abundant molecular alterations, while the most common mutations were observed in the TP53, CDK-, and KRAS genes. The most frequent ESCAT Tier In conclusion, we here present the successful molecular profiling and the framework for molecularly targeted treatments of gynecologic cancer patients in the FINPROVE trial. EudraCT 2021-000689-14; NCT05159245. Helsinki University Hospital. Cancer Foundation Finland has financially supported FINPROVE trial. Eschner Foundation has financially supported patient prescreening in Turku University Hospital. Roche Oy, Novartis Oy, Bayer Oy, Lilly Oy, Janssen-Cilag Oy are providing sixteen drugs as part of the clinical study. Pfizer Oy supporting the Molecular Tumor Board (MTB) development. A. Färkkilä: Financial Interests, Personal, Invited Speaker: GSK, AstraZeneca; Financial Interests, Institutional, Research Grant: GSK. H.J. Lassus: Financial Interests, Personal, Advisory Board: MSD, Eisai; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Institutional, Local PI, Trial MK3475-KeynoteC93: MSD. E. Alanne: Financial Interests, Personal, Invited Speaker: Roche, Bayer; Financial Interests, Personal, Advisory Board: Novartis, AbbVie; Financial Interests, Personal, Other, Producing training material: Roche; Financial Interests, Personal, Other, Salary from Roche from participation in data collection and analyzing.: Roche; Non-Financial Interests, Member of Board of Directors: Finnish Lymphoma Group. S.M.E. Iivanainen: Financial Interests, Personal, Advisory Board: MSD, BMS, Novartis, Roche; Financial Interests, Personal, Invited Speaker: Siemens Healthineers, AstraZeneca, Eisai; Financial Interests, Institutional, Local PI: BMS, Faron; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche; Financial Interests, Institutional, Other, Sub-investigator: MSD, GSK; Financial Interests, Personal and Institutional, Steering Committee Member, The Origama study: Roche; Financial Interests, Institutional, Coordinating PI: Roche; Other, Study Steering committee member: Hoffman-La Roche; Other, Consultant: Elekta. 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. All other authors have declared no conflicts of interest.Conclusions
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Funding
Disclosure
Resources from the same session
31P - Napabucasin transforms liver microenvironment and boosts immunotherapy efficacy by converting potential metastases into “hot” tumors
Presenter: Li Lin
Session: Poster session 07
32P - Patient derived circulating tumor cell clusters for personalized chemotherapy
Presenter: Prashant Kumar
Session: Poster session 07
Resources:
Abstract
33P - Anti-tumor effect of Debio 0432, a potent and selective USP1 inhibitor, in combination with PARP inhibitors
Presenter: Noémie Luong
Session: Poster session 07
34P - A novel gene family underlying cancer cell resilience
Presenter: David Amici
Session: Poster session 07
35P - The selective WEE1 inhibitor azenosertib shows synergistic anti-tumor effects in combination with topoisomerase I inhibitor-based antibody drug conjugates
Presenter: Jianhui Ma
Session: Poster session 07
36P - Branched-chain amino acids metabolism reprogramming in trastuzumab primary resistant HER2 positive breast cancer
Presenter: Yijia Hua
Session: Poster session 07
37P - A consensus gene set facilitates enrichment analysis of cancer hallmarks
Presenter: Otília Menyhart
Session: Poster session 07
38P - Feasibility of expanding tumor-infiltrating lymphocytes from cryopreserved tumor specimens after long-term storage
Presenter: Daria Kuznetsova
Session: Poster session 07
39P - Search for rare copy number variants associated with hereditary breast cancer in Finnish case-control cohorts
Presenter: Timo Kumpula
Session: Poster session 07
40P - STOPIN: A new approach to solve the hematological toxicity of antibody-drug conjugates (ADC) with soft topoisomerase inhibitor
Presenter: Xinghai Wang
Session: Poster session 07