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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): Tom John
- 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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Proffered Paper session II (ID 61)
- Event: ELCC 2019
- Type: Proffered Paper session
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 4/11/2019, 09:00 - 10:30, Room A
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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): Tom John
- 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.
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.
