64P - Entrectinib in locally advanced/metastatic ROS1 and NTRK fusion-positive non-small cell lung cancer (NSCLC): Updated integrated analysis of STARTRK-2, STARTRK-1 and ALKA-372-001

Background

Entrectinib is a systemic and central nervous system (CNS)-active potent inhibitor of ROS1 and TRKA/B/C. Primary data showed that entrectinib was tolerable and achieved high objective response rates (ORR) in patients (pts) with ROS1-positive (ROS1+), ROS1 inhibitor-naive NSCLC, and in pts with NTRK fusion-positive (NTRK+) NSCLC, including pts with baseline CNS disease. We present data from an additional 5 months of follow-up.

Methods

Pts with locally advanced/metastatic ROS1+ or NTRK+ tumors (with or without baseline CNS disease) confirmed by nucleic acid-based methods, enrolled in global 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 blinded independent central review (BICR) using RECIST v1.1, after cycle 1 (4 wks) then every 8 wks. Primary endpoints were ORR and duration of response (DOR) by BICR. Secondary endpoints included ORR and DOR in pts with or without baseline CNS disease, and safety. Intracranial (IC) ORR and DOR were evaluated in pts with baseline CNS disease.

Results

There were 53 efficacy-evaluable pts with treatment-naïve, ROS1+ NSCLC and 10 pts with NTRK+ NSCLC. As of 30 Oct 2018 (additional 5 months’ follow-up), BICR ORR: ROS1+ 79.2% (95% CI 65.9–89.2) and NTRK+ 70.0% (95% CI 34.75–93.33) with complete responses in 5 (9.4%) pts and 1 (10.0%) pt, respectively. In ROS1+ NSCLC, median DOR: 24.6 mo (95% CI 12.6–34.8); in pts with and without baseline CNS disease, ORR was 73.9% (95% CI 51.6–89.8) and 83.3% (95% CI 65.3–94.4); IC ORR was 55.0% (95% CI 31.5–76.9); and median IC DOR was 12.9 mo (95% CI 5.6–not estimable). Additional efficacy for NTRK+ NSCLC pts will be presented. Entrectinib was well tolerated with a safety profile consistent with that previously reported; there were no new or unexpected safety findings.

Conclusions

In line with the primary data, in pts with ROS1+ and NTRK+ NSCLC after an additional 5 months of follow-up, entrectinib was well tolerated and showed clinically meaningful, durable systemic and intracranial responses.

Clinical trial identification

ALKA-372-001 [EudraCT 2012-000148-88] STARTRK-1 [NCT02097810] STARTRK-2 [NCT02568267].

Editorial acknowledgement

Medical Writing support was provided by Laura Vergoz and Charlotte Kennerley, PhD of Gardiner-Caldwell Communications and was funded by F. Hoffmann-La Roche.

Legal entity responsible for the study

F. Hoffman-La Roche.

Funding

F. Hoffman-La Roche.

Disclosure

F. de Braud: Advisory / Consultancy, Officer / Board of Directors: TizianaLife Sciences, BMS, Celgene, Novartis, Servier, Pharm Research Associated, Daiichi Sankyo, Ignyta, Amgen, Pfizer, Octimet Oncology, Incyte, Teofarma, Pierre Fabre, Roche, EMD Serono ; Honoraria (self): BMS, Eli Lilly, Roche, Amgen, AstraZeneca, Gentili, Fondazione Menarini, Novartis, MSD, Ignyta, Bayer, Noema S.r.l., ACCMED, Dephaforum S.r.l., Nadirex, Roche, Biotechspert Ltd, PriME Oncology, Pfizer . S. Siena: Advisory / Consultancy: Amgen, Bayer, BMS, CheckmAb, Celgene, Daiichi-Sankyo, Incyte, Merck, Novartis, Roche-Genentech, and Seattle Genetics. F. Barlesi: Research grant / Funding (self), Travel / Accommodation / Expenses: Astra-Zeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, MSD, Pierre Fabre, Pfizer and Takeda; Research grant / Funding (institution): AbbVie, ACEA, Amgen, Astra-Zeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Eisai, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Genentech, Ipsen, Ignyta, Innate Pharma, Loxo, Novartis, Medimmune, Merck, MSD, Pierre Fabre, Pfizer, Sanofi-Aventis; Non-remunerated activity/ies: Principal Investigator for Astra-Zeneca, BMS, Merck, Pierre Fabre and Roche sponsored trials (or ISR). A. Drilon: Honoraria (self), Advisory / Consultancy: Ignyta/Genentech/Roche Loxo/Bayer/Lilly Takeda/Ariad/Millenium TP Therapeutics AstraZeneca Pfizer Blueprint Medicines Helsinn Beigene BergenBio Hengrui Therapeutics Exelixis Tyra Biosciences Verastem MORE Health; Research grant / Funding (institution): Pfizer Exelixis GlaxoSmithKlein Teva Taiho PharmaMar; Research grant / Funding (self): Foundation Medicine; Licensing / Royalties: Wolters Kluwer; Travel / Accommodation / Expenses: Merck - Food/Beverage Puma - Food/Beverage; Honoraria (self): Medscape, OncLive, PeerVoice, Physicians Education Resources, Targeted Oncology, Research to Practice. B. Simmons: Full / Part-time employment: Roche (Genentech). X. Huang: Shareholder / Stockholder / Stock options, Full / Part-time employment: Genentech. S. Osborne: Full / Part-time employment: Roche. R.C. Doebele: Shareholder / Stockholder / Stock options: Rain Therapeutics; Advisory / Consultancy: Chair of Scientific Advisory Board for Rain Therapeutics; Honoraria (self): Guardant; Advisory / Consultancy: Pfizer, Trovagene, Ariad, Takeda, AstraZeneca, Genentech/Roche, Ignyta, Loxo, Rain.; Research grant / Funding (self): Ignyta, Loxo, Mirati; Licensing / Royalties: Abbott Molecular, Rain Therapeutics, GVKbio, Chugai, Loxo, Ignyta, Genentech, Ariad, Foundation Medicine, Black Diamond.