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Jürgen Wolf
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Implementation of personalised lung cancer care in clinical routine (ID 33)
- Event: ELCC 2019
- Type: Special Symposium
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 4/12/2019, 10:30 - 12:00, Room A
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Experiences from the German Network Genomic Medicine (ID 87)
10:30 - 12:00 | Presenting Author(s): Jürgen Wolf
- Abstract
- Presentation
Abstract not provided
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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Lunch & Poster Display session (ID 58)
- Event: ELCC 2019
- Type: Poster Display session
- Track:
- Presentations: 5
- Moderators:
- Coordinates: 4/11/2019, 12:30 - 13:00, Hall 1
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132P - New insights into acquired resistance mechanisms to third-generation EGFR tyrosine kinase inhibitor therapy in lung cancer (ID 307)
12:30 - 13:00 | Author(s): Jürgen Wolf
- Abstract
Background
The emergence of acquired resistance (AR) against third-generation epidermal growth factor receptor tyrosine kinase inhibitors (TKI) remain a major clinical challenge in lung adenocarcinoma patients. Here we characterized the role of acquired resistance mechanism with a focus on inter-individual heterogeneity and co-occurring genetic aberrations. We could analyze pre- and post-treatment samples of patients treated with third-generation EGFR TKIs.
a9ded1e5ce5d75814730bb4caaf49419 Methods
We characterized 128 patients, which are EGFR p.T790M positive to early generation EGFR TKIs within thedatabases of the Network Genomic Medicine (NGM), the NOWEL network, the Department of Thoracic Oncology of the Netherlands Cancer Institute and the Vall d’Hebron University Hospital. In 60 patients, corresponding analyses of third generation EGFR TKI treatment outcomes and molecular analyses were practicable.
20c51b5f4e9aeb5334c90ff072e6f928 Results
Co-occurring aberrations were found in 75% of the samples with acquired resistance to early-generation TKI. TP53mutations were the most frequent aberrations detected. In MET, copy number variants were found (n = 6). In a subgroup, we identified 4 patients with the new EGFRresistance mutation p.G724S after third-generation TKI treatment. Still, loss of the EGFRp.T790M mutation and METamplification are the most common aberrations after third-generation TKI treatment.
fd69c5cf902969e6fb71d043085ddee6 Conclusions
EGFR inhibitors represent a powerful tool for precision cancer medicine in genetically selected patients. We could show in this study that additional genetic aberrations are frequent in the setting of AR to EGFR TKIs and may mediate innate and acquired resistance to third-generation EGFR TKIs. Amplification of METwas strongly associated with primary treatment failure and thus the strongest factor in innate resistance. AR to third-generation EGFR TKI (p.G724S) can possibly be overcome with second-generation EGFR TKI.
b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study
The authors.
213f68309caaa4ccc14d5f99789640ad Funding
Deutsche Forschungsgemeinschaft, Cluster of Excellence RESOLV, the Bundesministerium für Bildung und Forschung, Else Kröner-Fresenius Stiftung, Deutsche Krebshilfe, European Union, (NRW) as part of the EFRE initiative (EMODI, grant no. EFRE-0800397 to R.B. and M.L.S.) and by the German Ministry of Science and Education (BMBF) as part of the e:Med program (grant no. 01ZX1303A to R.B. and J.W). E.F. received funding by the Instituto de Salud Carlos III (PI17/00938), NEGECA, ITMC of TU Dortmund.
682889d0a1d3b50267a69346a750433d Disclosure
J. Fassunke: Honoraria: AstraZeneca. C. Heydt, S. Merkelbach-Bruse: Speaking honoraria: AstraZeneca. J. Wolf: Consulting, lecture fees: AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Ignyta, Lilly, MSD, Novartis, Pfizer, Roche; Funding for scientific research: BMS, Johnson&Johnson, MSD, Novartis, Pfizer. R. Buettner: Employee: Targos Molecular Pathology. M.L. Sos: Commercial research grant: Novartis. D. Rauh: Consultant, lecture fees: AstraZeneca, Merck-Serono, Takeda, Pfizer, Novartis, Boehringer Ingelheim, Sanofi-Aventis. All other authors have declared no conflicts of interest.
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134P - Mutational spectrum of acquired resistance to reversible versus irreversible EGFR tyrosine kinase inhibitors (ID 297)
12:30 - 13:00 | Author(s): Jürgen Wolf
- Abstract
Background
Mutational spectrum of acquired resistance to reversible versus irreversible EGFR tyrosine kinase inhibitors Over the past years, EGFR tyrosine kinase inhibitors (TKI) revolutionized treatment response. 1st-generation (reversible) EGFR TKI later the 2nd –generation irreversible EGFR TKI Afatinib was aimed to improve treatment response. Nevertheless, diverse resistance mechanisms develop within the first year of therapy. Here, we evaluate the prevalence of acquired resistance mechanisms towards reversible and irreversible EGFR TKI.
a9ded1e5ce5d75814730bb4caaf49419 Methods
Rebiopsies of patients after progression to EGFR TKI therapy (>6months) were targeted to histological and molecular analysis. Multiplexed targeted sequencing (NGS) was conducted to identify acquired resistance mutations (e.g. EGFR p.T790M). Further, Fluorescence in situ hybridisation (FISH) was applied to investigate the amplification status of bypass mechanisms like, MET or HER2.
20c51b5f4e9aeb5334c90ff072e6f928 Results
123 rebiopsy samples of patients that underwent firts-line EGFR TKI therapy ( PFS >6months) were histologically and molecularly profiled upon clinical progression. The EGFR p.T790M mutation ist the major mechanism of acquired resistance in patients treated with reversible as well as irreversible EGFR TKI. Nevertheless a statistically significant difference for the acquisition of T790M mutation has been idientified: 45% of afatinib- vs 65% of reversible EGFR TKI treated patients developed a T790M mutation (p-value 0.02). Progression free survival (PFS) was comparable in patients treated with irreversible EGFR irrespective of the sensitising primary mutation or the acquisition of p.T790M.
fd69c5cf902969e6fb71d043085ddee6 Conclusions
The EGFR p.T790M gatekeeper mutation ist he most prominent mechanism of resistance to reversible and irreversible EGFR TKI therapy. Nevertheless there is a statistically significant prevalence of p.T790M acquisition between the two types of TKI, which might be of importance for clinical therapy decision.
b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study
The authors.
213f68309caaa4ccc14d5f99789640ad Funding
Boehringer Ingelheim.
682889d0a1d3b50267a69346a750433d Disclosure
S. Wagener-Ryczek: Honoraria: Boehringer Ingelheim. C. Heydt: Honoraria: AstraZeneca, BMS, Illumina. S. Michels: Honoraria: Novartis, Pfizer, AstraZeneca, Boehringer Ingelheim; Advisory roles: Boehringer Ingelheim, Pfizer; Research funding: Pfizer, Novartis, BMS; Travel support/accommodations: Novartis. J. Fassunke: Honoraria, advisory role: AstraZeneca. M. Tiemann: Honoraria: Pfizer, Novartis, Roche. L. Heukamp: Co-founder: Neo New Oncology. J. Wolf: Honoraria: AstraZeneca, BMS, Clovis Oncology, Lilly, MSD, Novartis, Pfizer, Roche; Advisory roles: AstraZeneca, BMS, Clovis Oncology, Lilly, MSD, Novartis, Pfizer, Roche, Amgen. R. Buettner: Co-founder, Chief Scientific Officer: Targos Molecular Pathology; Honoraria: Roche, Pfizer, Novartis, AstraZeneca, Qiagen, MSD, BMS, Lilly. S. Merkelbach-Bruse: Honoraria: AstraZeneca; Advisory roles: AstraZeneca, Roche. All other authors have declared no conflicts of interest.
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147P - Impact on KRAS-subtypes and TP53 mutations on the prognostic value of KRAS/KEAP1 comutations in non-small cell lung cancer (NSCLC) (ID 493)
12:30 - 13:00 | Author(s): Jürgen Wolf
- Abstract
Background
Recent studies suggest a devastating impact of KEAP1 mutations on survival in systemically treated advanced NSCLC for both KRAS-comutated and KRAS-wildtype patients. KRAS G12C mutations differ in their co-mutational properties from other KRAS mutations, and TP53 mutations affect the outcome in a subset of NSCLC like ALK-positive NSCLC. We set out this analysis to determine the impact of both KRAS G12C and co-occurring TP53 mutations on the prognostic value of KRAS/KEAP1 comutations.
a9ded1e5ce5d75814730bb4caaf49419 Methods
We pooled the data from three different analyses between 2013 and 2018 and looked for patients with stage IV NSCLC for whom survival data was available and who received systemic therapy. The patients had to be diagnosed by a comprehensive next-generation sequencing panel, comprising at least KRAS, KEAP1and TP53 mutations. Median overall survival (mOS) was assessed using Kaplan Meier statistics.
20c51b5f4e9aeb5334c90ff072e6f928 Results
We identified 35 patients with KRAS/KEAP1 comutation and available survival data. G12C was detected in 22 patients (62.9%). A co-occurring TP53 mutation could be found in 15 patients (42.9%), and 11 patients (31.4%) presented with both aberrations beside a KEAP1 mutation. 15 patients (42.9%) had neither comutation. The mOS for the whole cohort was 9.8 months (95% CI, 6.3-13.3 months). Neither the presence of a G12C mutation (mOS 9.8 months [5.7-13.4], log rank p = 0.724) nor the presence of a co-occurring TP53 mutation (mOS 9.0 months [5.8-12.2], log rank p = 0.407) had a significant influence on the outcome. For G12C/TP53 beside KEAP1 mutations, there was hardly any difference to the comparison cohort (mOS 9.8 months [5.4-14.2], log rank p = 0.998). Patients without G12C and TP53 had an mOS of 10.4 months (3.6-17.2 months, log rank p = 0.467).
fd69c5cf902969e6fb71d043085ddee6 Conclusions
The comutation status of TP53 mutations and/or the presence of the KRAS G12C subtype have no impact on the prognostic value of KRAS/KEAP1-mutated stage IV NSCLC. Further investigations are ongoing to reveal the influence of the mode of systemic therapy in larger cohorts to confirm these findings.
b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study
The authors.
213f68309caaa4ccc14d5f99789640ad Funding
Has not received any funding.
682889d0a1d3b50267a69346a750433d Disclosure
All authors have declared no conflicts of interest.
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178P - Feasibility of O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET for treatment monitoring of brain metastases in lung cancer patients (ID 561)
12:30 - 13:00 | Author(s): Jürgen Wolf
- Abstract
Background
Brain metastases (BMs) occur frequently in patients with advanced lung cancer. So far, intracranial efficacy of systemic lung cancer treatment is nearly unpredictable. Contrast-enhanced magnetic resonance imaging (MRI) is considered gold standard for response assessment but lacks potential to discriminate between malignant or active tumor lesions from benign or postinflammatory signal alterations. O-(2- [18F]fluoroethyl)-L-tyrosine (FET)-positron emission tomography (PET) has shown additional diagnostic value over standard MRI in glioma patients. We set out this analysis to determine the feasibility of FET PET in lung cancer patients.
a9ded1e5ce5d75814730bb4caaf49419 Methods
FET with a mean activity of 200 MBq was produced and FET PET performed 20-40 minutes post injectionem at Research Center Juelich (Forschungszentrum Jülich). Patients with cerebral metastasized lung cancer underwent at least one tomography, and tumor volume and activity were assessed by both standard uptake values (SUVs) or tumor-to-brain ratios. A lesion-brain ratio in the standard uptake value (SUV) of more than 2 was considered pathological.
20c51b5f4e9aeb5334c90ff072e6f928 Results
From 2015 to 2018, 48 patients received at least one FET PET, whereof 11 patients (22.9%) underwent two scans and one patient three serial FET PETs. All scans could be analyzed for the assessment of tumor activity. The patients did not suffer of adverse events related to the tracer or the procedure. In most cases, FET PET was performed to discriminate between scar tissue and new tumor activity in singular metastases treated stereotactically. In a smaller number of patients, FET PET was used to assess treatment response in systematically treated patients.
fd69c5cf902969e6fb71d043085ddee6 Conclusions
FET PET is feasible in patients with brain metastases of lung cancer and might provide additional information to MRI for treatment decisions in these patients. Validation of the results and the reproducibility is ongoing.
b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study
The authors.
213f68309caaa4ccc14d5f99789640ad Funding
Has not received any funding.
682889d0a1d3b50267a69346a750433d Disclosure
All authors have declared no conflicts of interest.
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184TiP - FIND: A phase II study to evaluate the efficacy of erdafitinib in FGFR-altered squamous NSCLC (ID 571)
12:30 - 13:00 | Author(s): Jürgen Wolf
- Abstract
Background
Genomic FGFR alterations and their oncogenic driver potential are frequently observed in various cancers. Initial clinical trials with selective FGFR inhibitors showed moderate responses in FGFR amplified squamous NSCLC (sqNSCLC) patients. However, in FGFR mutated or translocated tumor types a response rate of above 30% was observed. Preclinical cell line and patient-derived sqNSCLC xenograft models with FGFR mutations or translocations indicate strong oncogenic activity and potential sensitivity to FGFR inhibitors. Approximately 3% of all sqNSCLC patients harbor somatic alterations within FGFR genes. However, only some of these mutations are shown to be oncogenic drivers in vitro and in vivo experiments or first in man trials.
a9ded1e5ce5d75814730bb4caaf49419 Trial design
Screening for FGFR mutations/translocations will be performed within the national Network of Genomic Medicine in 15 screening centers in Germany. SqNSCLC patients with activating FGFR genetic alterations will be treated in 11 clinical centers in Germany with the selective FGFR1-4 kinase inhibitor erdafitinib. Archival samples, fresh frozen tumor samples and blood for circulating tumor DNA will be collected before treatment and at time of progression. Patients will be treated until disease progression or unacceptable toxicity. The primary objective of the trial is to analyze the efficacy of erdafitinib in sqNSCLC patients with FGFR genetic driver alterations. Patients will be recruited into 3 cohorts: Cohort 1: high confidence activating FGFR translocations (max. 15 patients); Cohort 2: high confidence activating FGFR mutations (max. 15 patients); Cohort 3: low confidence activating FGFR alteration (ca. 20 patients). The study has been currently submitted by authorities and is currently targeted to start recruitment in Q1/2019.
d9b324a48b043b3d87bc9b3fe620f260 Clinical trial identification
EudraCT: 2018-000399-13.
7a6a3ffa2dadc03a6151ee2c4d6fa383 Legal entity responsible for the study
University of Cologne.
213f68309caaa4ccc14d5f99789640ad Funding
Janssen.
682889d0a1d3b50267a69346a750433d Disclosure
L. Nogova: Honoraria, advisory boards, travel fees: Boehringer Ingelheim, BMS, Celgene, Roche, Pfizer, Janssen, Novartis; Grants to institution: Pfizer, Novartis, BMS, Janssen. A. Hillmer: Honoraria, advisory board: MSD. S. Merkelbach-Bruse: Honoraria, advisory boards: Novartis, Roche. A. Pinto, C. Woempner: Grants to institution: BMS, Pfizer, Novartis, Janssen. R. Riedel: Honoraria, advisory boards: Boehringer Ingelheim, Novartis; Travel fee: Boehringer Ingelheim, Novartis, Lilly; Grants to institution: BMS, Pfizer, Novartis, Janssen. M. Scheffler: Honoraria, advisory boards: Boehringer Ingelheim; Grants to institution: Pfizer, BMS, Novartis, Janssen. S. Michels: Honoraria, Advisory boards: Novartis; Grants to institution: Pfizer, BMS, Novartis, Janssen. P. De Porre, A. Santiago-Walker: Employee: Janssen; Owning stock: J&J. R.N. Fischer: Honoraria: Bristol-Myers Squibb, MSD, Roche, Boehringer Ingelheim, Novartis, AstraZeneca; Grants to institution: Pfizer, BMS, Novartis, Janssen. D.S. Abdulla: Honoraria, advisory boards: Boehringer Ingelheim, Roche, AbbVie; Grants to institution: Pfizer, Novartis, BMS, Janssen. J. Wolf: Advisory boards, Honoraria, travel fees: AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Ignyta, Lilly, MSD, Novartis, Pfizer, Roche; Grants to institution: MSD, BMS, Pfizer, Novartis, Janssen. All other authors have declared no conflicts of interest.
cffcb1a185b2d7d5c44e9dc785b6bb25
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Mini Oral session I (ID 60)
- Event: ELCC 2019
- Type: Mini Oral session
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 4/11/2019, 08:00 - 08:50, Room A
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113O - Entrectinib in NTRK fusion-positive non-small cell lung cancer (NSCLC): Integrated analysis of patients (pts) enrolled in STARTRK-2, STARTRK-1 and ALKA-372-001 (ID 540)
08:00 - 08:50 | Author(s): Jürgen Wolf
- Abstract
- Presentation
Background
Neurotrophic receptor tyrosine kinase (NTRK) gene fusions lead to the expression of chimeric TRK proteins with constitutively activated kinase function, conferring oncogenic potential across several tumour types. Entrectinib is a CNS-active, potent inhibitor of TRKA/B/C and ROS1. We present integrated efficacy and safety data for entrectinib in NTRK fusion-positive (NTRK-FP) solid tumours focusing on pts with NSCLC.
a9ded1e5ce5d75814730bb4caaf49419 Methods
Pts with locally advanced/metastatic NTRK-FP tumours (with or without baseline CNS disease) confirmed by nucleic acid-based methods, enrolled in global (>150 sites, 15 countries) phase 1/2 entrectinib trials (ALKA-372-001 [EudraCT 2012-000148-88], STARTRK-1 [NCT02097810], STARTRK-2 [NCT02568267]) were included. Disease burden was assessed per BICR using RECIST v1.1, after cycle 1 (4 wks) then every 8 wks. Primary endpoints: ORR, DOR by BICR. Secondary endpoints: PFS, OS, and safety.
20c51b5f4e9aeb5334c90ff072e6f928 Results
Outcomes in the total efficacy-evaluable population (n = 54; 10 tumour types, >19 histopathologies) are shown in the table; responses were seen in all tumour types, median PFS 11.2 mo. In the cohort of pts with NTRK-FP NSCLC (n = 10), BICR ORR was 70% (7/10). In NSCLC pts with CNS disease per investigator at baseline (n = 6), 4 had an intracranial response (2 complete, 2 partial); 1 had stable disease and 1 was not evaluable. In the safety population (68 pts with NTRK-FP solid tumors who received at least 1 dose of entrectinib), most treatment-related adverse events (TRAEs) were grade 1–2; grade 3: 32.4%, grade 4: 2.9%; no grade 5 TRAEs. TRAEs resulted in discontinuation in 4.4% and dose reduction in 39.7% of pts.
fd69c5cf902969e6fb71d043085ddee6 Conclusions
In this integrated analysis of global multicentre clinical trials, entrectinib was well tolerated and induced clinically meaningful, durable systemic and intracranial responses in pts with NTRK-FP solid tumours, including those with NSCLC. (Table).
b651e8a99c4375feb982b7c2cad376e9 Clinical trial identification
ALKA-372-001 = EudraCT 2012-000148-88 – start date: 2015, trials ongoing STARTRK-1= NCT02097810 – start date: 2014, active, not recruiting (last update 2018) STARTRK-2 = NCT02568267 – start date: 2015, recruiting (last updated 2018).
7a6a3ffa2dadc03a6151ee2c4d6fa383 Editorial acknowledgement
Medical writing and editorial support was provided by Charlotte Kennerley, PhD of Gardiner-Caldwell Communications, Ashfield Healthcare Communications and sponsored by Roche in accordance with Good Publication Practice guidelines.
934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study
F. Hoffmann-La Roche.
213f68309caaa4ccc14d5f99789640ad Funding
Study Sponsor: Ignyta, Inc., a wholly owned subsidiary of F. Hoffmann-La Roche Ltd.
682889d0a1d3b50267a69346a750433d Disclosure
L. Paz-Ares: Honoraria: Lilly, MSD, BMS, Roche, PharmaMar, Merck, AstraZeneca, Novartis, BI, Celgene, Servier, Sysmex, Amgen, Incyte, Pfizer; Research: AZ, BMS, MSD; Advisory boards: Genomica; Scientific Chair/board member: Asociación Española Contra el Cáncer. R.C. Doebele: Sponsored research: Ignyta; Advisory boards: Roche, Ignyta, Takeda, AstraZeneca, Bayer; Stock ownership: Rain Therapeutics; Patent or biological material licensing fees: Ignyta, Abbott Molecular, Rain Therapeutics. A.F. Farago: Honoraria: Foundation Medicine, Clinical Care Options Oncology, Medical Learning Institute; Research: Ignyta, Loxo, AbbVie/Stemcentrx, PharmaMar, AZ, Novartis, Merck, BMS, Amgen; Consultant: Loxo, PharmaMar, AbbVie/Stemcentrx, Genentech, AZ, Bayer, Millennium. S.V. Liu: Research: Ignyta, Genentech, Pfizer, Threshold, Clovis, Corvus, Esanex, Bayer, OncoMed, Merck, Lycera, AZ, Molecular Partners, Rain Therapeutics; Advisory boards: Ignyta, Genentech, Pfizer, Takeda, Celgene, Lilly, Taiho, BMS, AZ, Regeneron, Merck. S.P. Chawla: Honoraria/research/Advisory boards: Amgen, Roche, GSK, Threshold Pharmaceuticals, CytRx Corporation, Ignyta, Immune Design, TRACON Pharma, Karyopharm Therapeutics, Sarc, Janssen. D. Tosi: Research funding: Novartis, Astellas, Janssen, Ipsen. C.M. Blakely: Research funding: Ignyta, Mirati, Novartis, Medimmune, Clovis. J.C. Krauss: Research funding: Boston Biomedical, AbbVie, Amgen, Isofol. D. Sigal: Advisory boards: Molecular Stethoscopye, Celularity, Curematch, Bayer; Research funding: Halozyme; Speakers bureau member: Celgene, Bayer; Stock ownership: BMS, Novartis, Halozyme. L. Bazhenova: Research funding: Beyongspring pharma; Stock ownership: EPIC Sciences; Advisory boards: Genentech, Takeda, AbbVie, Eli Lilly, Pfizer, AstraZeneca. T. John: Advisory boards: BMS, AstraZeneca, Boehringer Ingelheim, Takeda, Pfizer, Novartis, Merck, Ignyta, Roche. B. Besse: Research funding: AbbVie, Amgen, AstraZeneca, Biogen, Blueprint Medicines, BMS, Celgene, Eli Lilly, GSK, Ignyta, IPSEN, Merck KGaA, MSD, Nektar, Onxeo, Pfizer, Pharma Mar, Sanofi, Spectrum Pharmaceuticals, Takeda, Tiziana Pharma. J. Wolf: Advisory boards: AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Ignyta, Lilly MSD, Novartis, Pfizer, Roche; Corporate sponsorship for research: BMS, MSD, Novartis, Pfizer. T. Seto: Honoraria/research: Astellas, AZ, Bayer, BMS, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Kissei, Kyowa HakkoKirin, Merck Serono, Mochida, MSD, Nippon, Novartis, BI, NipponKayakuOno, Pfizer, Roche, Sanofi, ShowaYakuhinKako, Taiho, Takeda, YakultHonsha, Verastem. E. Chow-Maneval: Employee: Ignyta. C. Ye, B. Simmons: Employee: Genentech. G.D. Demetri: Advisory boards: Blueprint Medicines, Merrimack Pharmaceuticals, G1 Therapeutics, Caris Life Sciences, Champions Oncology; Consultant: Novartis, Pfizer, EMD-Serono, Sanofi Oncology, Janssen Oncology, Ignyta, Roche, Loxo Oncology, Mirati Therapeutics, Epizyme, PharmaMar, Daiichi Sankyo, WIRB Copernicus Group, ZioPharm, Polaris Pharmaceuticals, M.J.Hennessey/OncLive, G1 Therapeutics, Caris Life Sciences, Champions Oncology, Bessor Pharmaceuticals, Erasca Pharmaceuticals; Consulting fees: Novartis, Pfizer, EMD-Serono, Sanofi Oncology, Janssen Oncology, Ignyta, Roche, Loxo Oncology, Mirati Therapeutics, Epizyme, PharmaMar, Daiichi Sankyo, WIRB Copernicus Group, ZioPharm, Polaris Pharmaceuticals, M.J.Hennessey/OncLive, Blueprint Medicines, Merrimack Pharmaceuticals, G1 Therapeutics, Caris Life Sciences, Champions Oncology; Research support: Bayer, Novartis, Pfizer, Janssen Oncology, Ignyta, Roche, Loxo Oncology, AbbVie, Epizyme, Adaptimmune, GlaxoSmithKline; Patent licensing fees: Novartis; Equity: Blueprint Medicines, Merrimack Pharmaceuticals, G1 Therapeutics, Caris Life Sciences, Champions Oncology, Bessor Pharmaceuticals, Erasca Pharmaceuticals.
cffcb1a185b2d7d5c44e9dc785b6bb25Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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Opening and welcome (ID 4)
- Event: ELCC 2019
- Type: Opening and welcome
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 4/10/2019, 13:30 - 13:45, Room B
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Welcome to the Congress (ID 734)
13:30 - 13:45 | Presenting Author(s): Jürgen Wolf
- Abstract
- Presentation
Abstract not provided
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Proffered Paper session II (ID 61)
- Event: ELCC 2019
- Type: Proffered Paper session
- Track:
- Presentations: 2
- Moderators:
- Coordinates: 4/11/2019, 09:00 - 10:30, Room A
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Invited Discussant 21O and 108O (ID 670)
09:00 - 10:30 | Presenting Author(s): Jürgen Wolf
- Abstract
- Presentation
Abstract not provided
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109O - Entrectinib in locally advanced or metastatic ROS1 fusion-positive non-small cell lung cancer (NSCLC): Integrated analysis of ALKA-372-001, STARTRK-1 and STARTRK-2 (ID 501)
09:00 - 10:30 | Author(s): Jürgen Wolf
- Abstract
- Presentation
Background
Entrectinib is a potent ROS1 inhibitor (as well as TRKA/B/C), designed to effectively penetrate the central nervous system (CNS); brain metastases are common in patients (pts) with advanced ROS1 fusion-positive NSCLC. Entrectinib achieves therapeutic levels in the CNS with antitumour activity in multiple intracranial tumour models. We present updated integrated safety and efficacy data from three Phase 1/2 entrectinib studies (ALKA-372-001 [EudraCT 2012-000148-88], STARTRK-1 [NCT02097810], STARTRK-2 [NCT02568267]) in pts with locally advanced/metastatic ROS1 fusion-positive NSCLC.
a9ded1e5ce5d75814730bb4caaf49419 Methods
The analysis included pts with ROS1 inhibitor-naïve NSCLC harbouring a ROS1 fusion identified via nucleic acid-based diagnostic platforms. The ROS1 safety-evaluable population included pts who received ≥1 dose of entrectinib; the integrated efficacy analysis included pts with at least 6 months of follow-up. Tumour assessments were done at wk 4 and then every 8 wks by blinded independent central review (BICR), using RECIST v1.1. Primary endpoints by BICR: overall response rate (ORR), duration of response (DOR). Key secondary endpoints: progression-free survival (PFS), safety. Additional endpoints: intracranial ORR (complete/partial response), DOR in pts with intracranial response, PFS in pts with or without baseline CNS disease.
20c51b5f4e9aeb5334c90ff072e6f928 Results
In the ROS1 safety-evaluable population (n = 134), at least one treatment-related AE (TRAE) of any grade was seen in 93% of pts. Pts with at least one TRAE by highest grade were: grade 1/2, 59%; grade 3, 31%; grade 4, 4%. There were no grade 5 TRAEs. TRAEs led to dose reduction or discontinuation in 34% and 5% of pts, respectively. Efficacy outcomes are summarised in the table.
fd69c5cf902969e6fb71d043085ddee6 Conclusions
Entrectinib is highly active in pts with ROS1 fusion-positive NSCLC, including pts with CNS disease. Entrectinib is well tolerated with a manageable safety profile.
b651e8a99c4375feb982b7c2cad376e9 Clinical trial identification
ALKA-372-001 = EudraCT 2012-000148-88 – start date: 2015, trials ongoing STARTRK-1= NCT02097810 – start date: 2014, active, not recruiting (last update 2018) STARTRK-2 = NCT02568267 – start date: 2015, recruiting (last update 2018).
7a6a3ffa2dadc03a6151ee2c4d6fa383 Editorial acknowledgement
Medical writing and editorial support provided by Charlotte Kennerley PhD of Gardiner-Caldwell Communications, Ashfield Healthcare Communications and was sponsored by Roche in accordance with Good Publication Practice guidelines.
934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study
F. Hoffmann-La Roche.
213f68309caaa4ccc14d5f99789640ad Funding
Ignyta, Inc., a wholly owned subsidiary of F. Hoffmann-La Roche Ltd.
682889d0a1d3b50267a69346a750433d Disclosure
F. Barlesi: Honoraria: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Clovis Oncology, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, MSD, Pierre Fabre, Pfizer, Takeda. A. Drilon: Advisory boards: Bayer, Ignyta, Loxo Oncology, Pfizer, Roche/Genentech, TP Therapeutics; Research funding: Loxo Oncology. F. De Braud: Advisory boards: Novartis, Roche/Genetech, Merk Serono, Bristol-Myers Squibb, GlaxoSmithKline, BMS, Celgene, Servier, Ignyta, Pfizer, MSD, Philogen, AstraZeneca, Boehringer Ingelheim, Sanofi Aventis, Giscad, Italfarmaco, Eli Lilly, Amgen, Nadirex. S. Siena: Advisory boards: Amgen, Bayer, BMS, CheckmAb, Celgene, Incyte, Merck, Novartis, Roche and Seattle Genetics. M.G. Krebs: Honoraria for Advisory boards: Roche, Janssen, Octimet, Achilles therapeutics; Travel grants: AstraZeneca. C.C. Lin: Honoraria: AstraZeneca, BeiGene, Daiichi Sankyo, Novartis, Roche; Advisory boards: Blueprint, Boehringer Ingelheim, Novartis. T. John: Advisory boards: BMS, AstraZeneca, Boehringer, Takeda, Pfizer, Novartis, Merck, Ignyta, Roche. D.S.W. Tan: Grants and honoraria for Advisory boards: Novartis, Bayer, Boehringer Ingelheim, Merck, AstraZeneca, BMS, Roche, Pfizer and grants from GSK, Novartis, AstraZeneca. T. Seto: Honoraria/research: Astellas, AZ, Bayer, BMS, Chugai, Daiichi Sankyo, Eisai, EliLilly, Kissei, Kyowa HakkoKirin, MerckSerono, Mochida, MSD, Nippon, Novartis, BI, NipponKayakuOno, Pfizer, Roche, Sanofi, ShowaYakuhinKako, Taiho, Takeda, YakultHonsha, Verastem. R. Dziadziuszko: Honoraria, consulting fees: Roche, Pfizer, Boehringer Ingelheim, Clovis Oncology, Novartis, AstraZeneca, Tesaro. H-T. Arkenau: Employee: HCA; Advisory boards: Beigene, Guardant Health, Bicycle. C. Rolfo: Honoraria, Advisory boards: Mylan, Novartis, MSD, GuardantHealth, AstraZeneca. J. Wolf: Corporate sponsored research: BMS, MSD, Novartis, Pfizer; Advisory boards: AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Ignyta, Lilly MSD, Novartis, Pfizer, Roche. C. Ye, T. Riehl, S. Eng: Employee: Genentech. R.C. Doebele: Research: Ignyta; Advisory boards; Roche, Ignyta, Takeda, AstraZeneca, Bayer; Stock ownership: Rain Therapeutics; Patent or biological material licensing fees: Ignyta, Abbott Molecular, Rain Therapeutics. All other authors have declared no conflicts of interest.
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