122P - Molecular testing, treatment, and response of patients with advanced solid tumors harboring an NTRK gene fusion: Second interim results of the REALTRK registry

Background

Neurotrophic Tyrosine Receptor Kinase gene fusions are oncogenic drivers involving either NTRK1, NTRK2 or NTRK3 (encoding the tropomyosin receptor kinases TRKA, TRKB and TRKC, respectively). The overall prevalence of NTRK fusion-positive tumors is ∼0.30%, though frequencies vary by tumor type, with >90% reported for some rare tumor types such as secretory carcinoma of the breast and salivary glands. In Europe the TRK inhibitors (TRKi) entrectinib and larotrectinib, have both received tumor-agnostic approval based on pooled data of non-comparative phase I/II clinical trials with limited patient numbers, both showing high clinical activity and favorable safety profiles.

Methods

REALTRK is a retro- and prospective, observational, intersectoral, multicenter cohort study in Germany and Switzerland (NCT04557813) investigating patients (pts) with advanced solid tumors harboring an NTRK fusion diagnosed with a validated assay according to ESMO recommendations. Enrollment of 120 pts is planned. Pts with detailed information on NTRK testing qualify for complete documentation, including demographic and clinical characteristics, details on NTRK testing, treatment, outcome, and safety of TRKi. Furthermore, physician-reported factors on NTRK testing and treatment decision making as well as patient-reported outcomes on quality of life (EORTC QLQ-C30) are assessed.

Results

At data cut-off (Apr 28^th, 2023), 32 pts have been enrolled at 20 sites in Germany and Switzerland. 16 pts were eligible for complete documentation. Significant heterogeneity regarding pts, tumor types, and NTRK fusions was observed, including pts with ECOG status between 0 and 3, 7 different tumor entities, and 11 different NTRK1/2/3-fusion partners.

Conclusions

The tumor-agnostic cohort study REALTRK provides a challenging and unique opportunity to collect extremely rare and valuable data on NTRK testing and treatment reality of a very small pts population with NTRK fusion-positive solid tumors. Although the heterogeneity between pts and tumor types makes interpretation of the data and comparison to clinical trial data difficult, REALTRK offers the opportunity to collect important real-world evidence.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

iOMEDICO AG.

Funding

Roche Pharma GmbH.

Disclosure

S. Lange: Financial Interests, Institutional, Research Grant: Illumina, Inc.; Financial Interests, Institutional, Invited Speaker: Janssen-Cilag GmbH, MSD Sharp & Dohme GmbH, FALKFoundation e.v.B. Kasenda: Financial Interests, Personal, Invited Speaker: Roche Pharma GmbH; Financial Interests, Institutional, Advisory Board: Roche Pharma GmbH, Astellas Pharma GmbH. M. Zaiss: Financial Interests, Personal and Institutional, Speaker’s Bureau: AbbVie, MSD Sharp & Dohme GmbH, Roche Pharma GmbH, Takeda, Vifor; Financial Interests, Institutional, Advisory Board: AbbVie, AstraZeneca, BMS, Celgene, Eisai, Gilead, Hexal, Janssen-Cilag GmbH, Lilly, Novartis, Pfizer, Roche Pharma GmbH, Vifor. U.M. Martens: Financial Interests, Institutional, Advisory Board: BMS, Roche Pharma GmbH, GSK, Novartis, Pierre Fabre, Guardant Health, MSD Sharp & Dohme GmbH. C. Batereau: Financial Interests, Personal, Invited Speaker: Roche Pharma GmbH. T. Decker: Financial Interests, Personal and Institutional, Advisory Board: Novartis Pharma GmbH, iOMEDICO AG. O. Waidmann: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Bayer, BMS, Eisai, Ipsen, MSD, Novartis, Roche; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, BMS, Celgene, Eisai, Incyte, Ipsen, Janssen, Merck Serono, MSD, Novartis, Pierre Fabre, Roche, Servier; Financial Interests, Personal, Research Grant: Medac, Merck KGaA. C. Vannier: Financial Interests, Personal, Full or part-time Employment: Pierre Fabre Pharma GmbH. All other authors have declared no conflicts of interest.