Abstract 540P
Background
Entrectinib is a potent, CNS-active ROS1/TRK/ALK inhibitor, which induces clinically meaningful responses in pts with ROS1 fusion-positive (ROS1+) NSCLC and NTRK fusion-positive (NTRK+) solid tumours. We conducted an exploratory analysis to determine if number of prior lines of systemic therapy had any impact on response to entrectinib.
Methods
Patients with locally advanced/metastatic ROS1+ NSCLC or NTRK+ solid tumours (with/without baseline CNS metastases), enrolled in global phase I/II entrectinib trials (ALKA-372-001 [EudraCT 2012-000148-88], STARTRK-1 [NCT02097810], STARTRK-2 [NCT02568267]) were included. Response was assessed by blinded independent central review using RECIST v1.1 after 4 wks and then every 8 wks. Objective response rate (ORR) was calculated according to number of prior lines of systemic therapy.
Results
161 pts with ROS1+ NSCLC (data cut-off: 1 May 2019; median treatment duration 10.7mo) and 74 pts with NTRK+ solid tumours (data cut-off: 31 Oct 2018; median treatment duration 8.6 mo) were included. In the ROS1+ NSCLC cohort, ORR (n/N; 95% CI) was 64.4% (65/101; 54.2–73.6) in pts who had received prior systemic therapy in the metastatic setting, and 71.7% (43/60; 58.6–82.6) in those who had not. In the NTRK+ solid tumour cohort, corresponding ORRs were 57.4% (31/54; 43.2–70.8) and 80.0% (16/20; 56.3–94.3), respectively. ORR for the two cohorts according to number of prior lines of systemic therapy since metastatic disease diagnosis are presented (Table).
Conclusions
While pt numbers are relatively small, these data demonstrate similar responses to entrectinib in pts with ROS1+ NSCLC and NTRK+ solid tumours regardless of prior therapy exposure, supporting its use irrespective of number of prior lines of systemic therapy; ORR was >70% in pts receiving entrectinib as first-line therapy. Table: 540P
| Prior lines of systemic therapy in the metastatic setting* | ROS1+ NSCLC (N=94)† | NTRK+ solid tumours (N=74)‡ | ||
| N | ORR, % (n; 95% CI) | N | ORR, % (n; 95% CI) | |
| 0 | 31 | 83.9 (26; 66.3–94.6) | 20 | 80.0 (16; 56.3–94.3) |
| 1 | 38 | 63.2 (24; 46.0–78.2) | 21 | 61.9 (13; 38.4–81.9) |
| 2 | 13 | 69.2 (9; 38.6–90.9) | 20 | 65.0 (13; 40.8–84.6) |
| ≥3 | 12 | 83.3 (10; 51.6–97.9) | 13 | 38.5 (5; 13.9–68.4) |
*Pts may have received other therapies in the adjuvant or neoadjuvant setting that would not count as a line of therapy in this population. †Median duration of entrectinib exposure: 15.8 mos (IQR: 6.05–21.72). ‡Median duration of entrectinib exposure: 8.6 mos (IQR: 4.76–14.65).
Clinical trial identification
ALKA-372-001 (EudraCT 2012-000148-88); STARTRK-1 (NCT02097810); STARTRK-2 (NCT02568267).
Editorial acknowledgement
Third-party medical writing assistance, under the direction of the authors, was provided by Alix Biancardi, of Gardiner-Caldwell Communications, and was funded by F. Hoffmann-La Roche Ltd.
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
Funding
F. Hoffmann-La Roche Ltd.
Disclosure
S.V. Liu: Advisory/Consultancy: AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Catalyst, Celgene, G1 Therapeutics, Genentech/Roche, Guardant Health, Inivata, Janssen, Lilly, LOXO, MSD, Pfizer, PharmaMar, Regeneron, Takeda; Research grant/Funding (institution): Alkermes, AstraZeneca, Bayer, Blueprint, Bristol-Myers Squibb, Corvus, Genentech, Lilly, Lycera, Merck, Merus, Molecular Partners, Pfizer, Rain, RAPT, Spectrum, Turning Point Therapeutics; Travel/Accommodation/Expenses: AstraZeneca, Genentech/Roche, MSD. F. De Braud: Advisory/Consultancy: Bristol-Myers Squibb, Eli Lilly, Roche, Amgen, AstraZeneca, Istituto Gentili, Fondazione Internazionale Menarini, Octomet Oncology, Novartis, Merck Sharp & Dohme, Ignyta, Bayer, Noema, ACCMED, Dephaforum, Nadirex, Biotechspert, Pfizer; Speaker Bureau/Expert testimony: Bristol-Myers Squibb, Roche, Merck Sharp & Dohme, Ignyta, Dephaforum, prIME Oncology, Pfizer, Biotechespert; Research grant/Funding (institution): Roche, Novartis, Merck Sharp & Dohme, Bristol-Myers Squibb, Pfizer, Kymab, Celgene, Tesaro; Travel/Accommodation/Expenses: Bristol-Myers Squibb, Roche, Celgene, Amgen; Advisory/Consultancy: Tiziana Life Sciences, Pierre Fabre. A. Drilon: Honoraria (institution): Ignyta/Roche/Genentech, Loxo/Bayer/Lily, TP Therapeutics, AstraZeneca, Pfizer, Blueprint, Takeda/Ariad/Millennium, Helsinn, BeiGene, BerGenBio, Hengrui, Exelixis, Tyra, Verastem, MORE Health, AbbVie, 14ner/Elevation Oncology, Axis, Peerview Institute; Research grant/Funding (self): Foundation Medicine; Research grant/Funding (institution): Pfizer, Exelixis, Taiho, Teva, GlaxoSmithKline and Pharmamar; Licensing/Royalties: Wolters Kluwer; Honoraria (institution): OncLive, Paradigm Medical Communications, Remedica Ltd, ArcherDX, Foundation Medicine, PeerVoice, Research to Practice, Medscape, WebMD. R.C. Doebele: Advisory/Consultancy: Ignyta, Genentech/Roche, Loxo Oncology, Bayer, Eli Lilly, AstraZeneca, Pfizer, Blueprint Medicines, Anchiano, and Rain Therapeutics; Research grant/Funding (institution): Ignyta, Loxo, Mirati, Pfizer, Eli Lilly, and Strategia; Travel/Accommodation/Expenses: Ignyta, Genentech/Roche, Eli Lilly, Pfizer, Blueprint Medicines, and Rain Therapeutics; Shareholder/Stockholder/Stock options: Rain Therapeutics; Licensing/Royalties, Patent and biologic material licensing fees: Ignyta, Loxo, Abbott Molecular, Genentech/Roche, Chugai, Foundation Medicine, Black Diamond, and Rain Therapeutics, Voronoi, Pearl River, Ariad. M.R. Patel: Advisory/Consultancy: Nektar Therapeutics; Research grant/Funding (self): Merck, Vyriad and Fate Therapeutics. B.C. Cho: Advisory/Consultancy: Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD, Janssen, Medpacto, Blueprint medicines, KANAPH Therapeutic Inc; Research grant/Funding (institution): Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, AbbVie, Medpacto, GI-Innovation, Eli Lilly, Blueprint medicines; Shareholder/Stockholder/Stock options: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc; Licensing/Royalties: Champions Oncology; Officer/Board of Directors: Daan biotherapeutics. M-J. Ahn: Honoraria (self): AstraZeneca, Lilly, Takeda, Roche, MSD; Advisory/Consultancy: AstraZeneca, Lilly, Takeda, Roche, MSD, Merck, Boehringer Ingelheim, Ono Pharmaceutical, Bristol-Myers Squibb, and Alpha Pharmaceutical, Progeneer. C-H. Chiu: Honoraria (self): Pfizer, AstraZeneca/MedImmune, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai Pharmaceutical, Eli Lilly, MSD, Novartis, Ono Pharmaceutical, and Roche; Advisory/Consultancy: AstraZeneca/MedImmune, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai Pharmaceutical, MSD, Novartis, Ono Pharmaceutical, and Roche. A.F. Farago: Honoraria (self): DAVA Oncology, Clinical Care Options, Medical Learning Institute, Medscape, PeerView, Research to Practice; Advisory/Consultancy: Bayer, Loxo Oncology, Inc., Genentech, Roche, Bristol-Myers Squibb, AstraZeneca, AbbVie, PharmaMar, Boehringer Ingelheim, Merck, H3 Biomedicine, Pfizer, Syros; Research grant/Funding (self): Bayer, Loxo Oncology, Inc., Genentech, Roche, Bristol-Myers Squibb, AstraZeneca, AbbVie, PharmaMar, Merck, Ignyta, Amgen, Novartis. K. Goto: Honoraria (self): Astellas Pharma Inc.; AstraZeneca; Boehringer Ingelheim; Bristol-Myers Squibb; Chugai Pharma; Daiichi Sankyo Co., Ltd.; Guardant Health Inc.; IQVIA Services Japan K.K.; Janssen Pharmaceutical K.K.; Kyowa Hakko Kirin Co. Ltd; Life Technologies; Lilly; MSD; Advisory/Consultancy: Amgen Inc; Otsuka Pharma; Research grant/Funding (institution): Amgen Inc; Astellas Pharma; AstraZeneca; Boehringer Ingelheim; Bristol-Myers Squibb; Chugai Pharma; Daiichi Sankyo; Eisai; Ignyta; Janssen; Kyowa Hakko Kirin; Life Technologies; Lilly; Loxo; Medical & Biological Laboratories Co., LTD.; Merck Serono; MSD; Honoraria (self): Nippon Kayaku; Novartis; Ono Pharmaceutical; Otsuka Pharmaceutica; Pfizer; Taiho Pharmaceutical; Takeda; Research grant/Funding (institution): Novartis; Ono Pharmaceutical; Pfizer; Riken Genesis; Sumitomo Dainippon; Sysmex Corporation; Taiho Pharmaceutical; Takeda; Xcoo. J. Lee: Advisory/Consultancy: Oncologie, Seattle Genetics; Research grant/Funding (self): AstraZeneca, Eli Lilly & Company, Merck Sharp & Dohme. Y. Ohe: Honoraria (self): AstraZeneca, Chugai, Eli Lilly, ONO, BMS, Boehringer Ingelheim, Bayer, Pfizer, MSD, Taiho, Nippon Kayaku, Kyowa Hakko Kirin; Advisory/Consultancy: AstraZeneca, Chugai, ONO, BMS, Kyorin, Celltrion, Amgen, Nippon Kayaku; Research grant/Funding (institution): AstraZeneca, Chugai, Lilly, ONO, BMS, Kyorin, Dainippon-Sumitomo, Pfizer, Taiho, Novartis, Kissei, Ignyta, Takeda, Kissei, Daiichi-Sankyo, Janssen, LOXO; Officer/Board of Directors: JSMO, JLCS. S-H.I. Ou: Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer, Roche/Genentech, AstraZeneca, Takeda/ARIAD, Daiichi Sankyo; Research grant/Funding (institution): Pfizer, Roche/Genentech, AstraZeneca, Takeda/ARIAD, Daiichi Sankyo, Janssen, Mirati, Revolution Medicine, Lilly/LOXO Oncology, BluePrint Medicine; Shareholder/Stockholder/Stock options: Turning Point Therapeutics. P. Cassier: Honoraria (self): Novartis, Roche/Genentech, Blueprint Medicines, Amgen, AstraZeneca, Merck Serono; Honoraria (institution): Celgene, Plexxikon, AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Taiho Pharmaceutical, Toray Industries, Transgene, Loxo, GlaxoSmithKline, Innate Pharma, Janssen; Travel/Accommodation/Expenses: Roche, Amgen, Novartis, Bristol-Myers Squibb, Merck Sharp & Dohme, Netris Pharma. D.S.W. Tan: Honoraria (self): Novartis, Bayer, Boehringer Ingelheim, Celgene, AstraZeneca, Eli Lilly, and Loxo; Research grant/Funding (institution): Novartis, Bayer, AstraZeneca, Pfizer, and GlaxoSmithKline; Travel/Accommodation/Expenses: Novartis, Boehringer Ingelheim, Celgene, Merck, Pfizer, Roche, and Takeda. G.A. Otterson: Advisory/Consultancy: Pfizer, Genentech, AstraZeneca, Takeda, Guardant and Novocure; Speaker Bureau/Expert testimony: OncLive; Research grant/Funding (institution): AstraZeneca, Pfizer, Bristol-Myers Squibb, Genentech, Ignyta, and Merck. L. Veronese: Full/Part-time employment: F. Hoffmann-La Roche Ltd. S. Osborne: Full/Part-time employment: Roche. B. Simmons: Shareholder/Stockholder/Stock options: Roche/Genentech; Full/Part-time employment: Genentech/Roche. S. Siena: Advisory/Consultancy: Amgen, Bayer, BMS, CheckMab, Celgene, Daiichi Sankyo, Incyte, Merck, Novartis, Roche, and Seattle Genetics.