Abstract 64P
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.
Resources from the same session
528P - High-biologically effective dose radiotherapy may improve local control of small cell lung cancer patients with brain metastases: A propensity-matching analysis
Presenter: Qingyang Zhuang
Session: Poster display session
Resources:
Abstract
530P - Prognostic value of C-reactive protein, albumin and C-reactive protein to albumin ratio in small cell lung cancer: A meta-analysis
Presenter: Carla Emille Barbon
Session: Poster display session
Resources:
Abstract
531TiP - CANOPY-A: A phase III, placebo-controlled study of canakinumab as adjuvant therapy in patients (pts) with surgically resected NSCLC
Presenter: Byoung Chul Cho
Session: Poster display session
Resources:
Abstract
532TiP - CANOPY-1: A phase III, placebo-controlled study of pembrolizumab (PEM) plus platinum-based doublet chemotherapy (Ctx) with/without canakinumab in untreated patients (pts) with stage IIIB/IIIC-IV NSCLC
Presenter: Daniel Shao Weng Tan
Session: Poster display session
Resources:
Abstract
533TiP - CANOPY-2: A phase III, placebo-controlled study of canakinumab with or without docetaxel in patients (pts) with NSCLC previously treated with PD-(L)1 inhibitors and platinum-based chemotherapy (Ctx)
Presenter: Darren Lim
Session: Poster display session
Resources:
Abstract
534TiP - A randomized phase III study of carboplatin plus nab-paclitaxel with or without nintedanib for NSCLC with IPF (J-SONIC)
Presenter: Kohei Otsubo
Session: Poster display session
Resources:
Abstract
535TiP - Phase II study of atezolizumab for pretreated advanced / recurrent non-small cell lung cancer with idiopathic interstitial pneumonia (TORG1936 / AMBITIOUS study)
Presenter: Satoshi Ikeda
Session: Poster display session
Resources:
Abstract
536TiP - INSIGHT 2: Tepotinib plus osimertinib in patients with EGFR-mutant NSCLC having acquired resistance to EGFR TKIs due to MET-amplification: A phase II trial in progress study
Presenter: James C-H Yang
Session: Poster display session
Resources:
Abstract
YO8 - Carcinosarcoma of the Breast in a Filipino Female: A Case Report
Presenter: Ma. Angelle Lalaine Dantes
Session: Poster display session
Resources:
Abstract
YO9 - Small Malignant Phyllodes Tumor of the Breast with Metastases to the Lung and Bone
Presenter: Gusti Harti
Session: Poster display session
Resources:
Abstract