Abstract 1431P
Background
The national network genomic medicine lung cancer (nNGM) improves patient care of non-small cell lung cancer (NSCLC) patients by applying harmonized state-of-the-art molecular testing. Patients with actionable alterations can benefit from targeted molecular therapy options. However, systematic molecular testing frequently also leads to the discovery of mutations with no clear clinical actionability, commonly classified as variants of unknown significance (VUS). Since individual VUS are often rare, generation of evidence from clinical trials is difficult. The preclinical platform of the nNGM aims to provide functional data on VUS by combining preclinical research efforts with clinical data available from the nNGM network, thereby generating evidence for patients with VUS.
Methods
Clinicians can contact the preclinical platform with characterization requests for VUS. An expert team compiles literature data, clones the mutations into in vitro model systems, and conducts functional testing for oncogenicity and resistance mechanisms. Results are recorded in the MURIPEDIA knowledge data base, and correlation of predicted treatment sensitivity and clinical response informs a self-learning, evidence-generating system. The service is integrated with individual and collaborative research activities of the contributing groups for the systematic generation of preclinical evidence and includes computational methods for driver detection, and the setup of organoid biobanks as the groundwork for future patient-derived in vitro models.
Results
A total of 32 on-demand requests have been processed by scientists from the preclinical platform. Specialized in vitro testing with a turnaround time of 6 – 12 weeks is available for VUS occurring in EGFR, FGFR1, FGFR2, FGFR3, FGFR4, ROS1, or BRAF. From 19 requests concerning VUS of EGFR with no prior available data, 6 novel EGFR in vitro drivers were identified and profiled.
Conclusions
The nNGM preclinical platform offers a comprehensive on-demand characterization service for VUS in NSCLC patients supporting the concept of knowledge-generating patient care in the nNGM.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Deutsche Krebshilfe (German Cancer Aid).
Disclosure
F.C. Saalfeld: Financial Interests, Personal, Advisory Role: Janssen, Lilly, AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca, Takeda, Pfizer, Novartis; Financial Interests, Personal, Writing Engagement: Thieme; Financial Interests, Institutional, Research Funding: Roche. A. Hillmer: Financial Interests, Institutional, Research Funding: Dracen. L. Nogova: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Novartis, Pfizer, Takeda, Roche; Financial Interests, Institutional, Other, IIT funding: Pfizer, MSD, Dracen, Bristol Myers Squibb; Financial Interests, Institutional, Other, IIT: Pfizer, MSD, Dracen, Bristol Myers Squibb, Amgen. J. Wolf: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Blueprint, BMS, Boehringer Ingelheim, Daiichi Sankyo, Ignyta, Janssen, Lilly, Loxo, MSD, Novartis, Pfizer, Roche, Seattle Genetics, Takeda; Financial Interests, Personal, Invited Speaker: Bayer, Chugai; Financial Interests, Institutional, Research Grant: BMS, Janssen, Novartis, Pfizer. S. Diederichs: Financial Interests, Personal, Stocks or ownership: siTOOLs. T. Brummer: Financial Interests, Personal, Expert Testimony: Institut National du Cancer; Financial Interests, Personal, Other: ESMO, Actelion. R. Büttner: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Illumina, Janssen, Lilly, Merck-Serono, MSD, Novartis, Qiagen, Pfizer, Roche, Sanofi; Financial Interests, Personal, Stocks or ownership: Gnothis Inc SE, Timer Therapeutics. M. Janning: Financial Interests, Personal, Advisory Role: AstraZeneca, Roche, Amgen, Takeda, BMS, Novartis. S. Loges: Financial Interests, Personal, Invited Speaker: BerGenBio AS, BMS, Eli Lilly, Boehringer Ingelheim, Roche Pharma, Medac GmbH, Sanofi Aventis, Novartis, AstraZeneca, Pfizer, Takeda, Amgen, Janssen, Merck, MSD, Daiichi Sankyo, Bayer; Financial Interests, Personal, Advisory Board: BerGenBio AS, BMS, Eli Lilly, Boehringer Ingelheim, Roche Pharma, Sanofi Aventis, Novartis, AstraZeneca, Pfizer, Takeda, Amgen; Financial Interests, Institutional, Coordinating PI: BerGenBio AS; Financial Interests, Institutional, Research Grant: BMS, Eli Lilly, Roche Pharma, ADC Therapeutics, Daiichi Sankyo; Non-Financial Interests, Member: DGHO, AIO, ASCO. All other authors have declared no conflicts of interest.
Resources from the same session
1411P - Tusamitamab ravtansine plus ramucirumab as 2L therapy or beyond in patients with metastatic NSq NSCLC and high CEACAM5 expression (CARMEN-LC04)
Presenter: Grace Dy
Session: Poster session 20
1412P - SAKK 17/18-ORIGIN trial: Efficacy and safety from a multicenter phase II trial of gemcitabine and atezolizumab in patients with advanced NSCLC progressing on immune checkpoint inhibitors
Presenter: Alessandra Curioni-Fontecedro
Session: Poster session 20
1414P - Impact of co-mutations on the prognosis of targeted therapy in EGFR-mutant advanced NSCLC: A result of real-world study
Presenter: Sisi Pan
Session: Poster session 20
1416P - Recurrence of infusion-related reaction (IRRs) associated to avimantamab
Presenter: Maria Virginia Sanchez Becerra
Session: Poster session 20
1417P - Change in healthcare resource use and associated costs of patients with metastatic lung cancer between 2013 and 2019: An observational study from the French national claims database
Presenter: Christos Chouaid
Session: Poster session 20
1418P - Impact of TTFields therapy on global and functional health-related quality of life (HRQoL) in metastatic non-small cell lung cancer (mNSCLC) from the pivotal LUNAR study
Presenter: Rupesh Kotecha
Session: Poster session 20
1419P - TACSTD2 (Trop-2) constitutes a promising antibody-drug conjugate target for patients with non-small cell lung cancer brain metastases
Presenter: Sara Hijazo-Pechero
Session: Poster session 20
1420P - Real-life management of octogenarians with NSCLC in a French nationwide cohort
Presenter: Romain Corre
Session: Poster session 20
1421P - AI-powered intracranial tumor response predicts systemic progression with high concordance in endpoint evaluation in the phase III CROWN study
Presenter: Shao-Lun Lu
Session: Poster session 20