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Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials.

Authors :
Doebele, Robert C
Doebele, Robert C
Drilon, Alexander
Paz-Ares, Luis
Siena, Salvatore
Shaw, Alice T
Farago, Anna F
Blakely, Collin M
Seto, Takashi
Cho, Byung Chul
Tosi, Diego
Besse, Benjamin
Chawla, Sant P
Bazhenova, Lyudmila
Krauss, John C
Chae, Young Kwang
Barve, Minal
Garrido-Laguna, Ignacio
Liu, Stephen V
Conkling, Paul
John, Thomas
Fakih, Marwan
Sigal, Darren
Loong, Herbert H
Buchschacher, Gary L
Garrido, Pilar
Nieva, Jorge
Steuer, Conor
Overbeck, Tobias R
Bowles, Daniel W
Fox, Elizabeth
Riehl, Todd
Chow-Maneval, Edna
Simmons, Brian
Cui, Na
Johnson, Ann
Eng, Susan
Wilson, Timothy R
Demetri, George D
trial investigators
Doebele, Robert C
Doebele, Robert C
Drilon, Alexander
Paz-Ares, Luis
Siena, Salvatore
Shaw, Alice T
Farago, Anna F
Blakely, Collin M
Seto, Takashi
Cho, Byung Chul
Tosi, Diego
Besse, Benjamin
Chawla, Sant P
Bazhenova, Lyudmila
Krauss, John C
Chae, Young Kwang
Barve, Minal
Garrido-Laguna, Ignacio
Liu, Stephen V
Conkling, Paul
John, Thomas
Fakih, Marwan
Sigal, Darren
Loong, Herbert H
Buchschacher, Gary L
Garrido, Pilar
Nieva, Jorge
Steuer, Conor
Overbeck, Tobias R
Bowles, Daniel W
Fox, Elizabeth
Riehl, Todd
Chow-Maneval, Edna
Simmons, Brian
Cui, Na
Johnson, Ann
Eng, Susan
Wilson, Timothy R
Demetri, George D
trial investigators
Source :
The Lancet. Oncology; vol 21, iss 2, 271-282; 1470-2045
Publication Year :
2020

Abstract

BackgroundEntrectinib is a potent inhibitor of tropomyosin receptor kinase (TRK) A, B, and C, which has been shown to have anti-tumour activity against NTRK gene fusion-positive solid tumours, including CNS activity due to its ability to penetrate the blood-brain barrier. We present an integrated efficacy and safety analysis of patients with metastatic or locally advanced solid tumours harbouring oncogenic NTRK1, NTRK2, and NTRK3 gene fusions treated in three ongoing, early-phase trials.MethodsAn integrated database comprised the pivotal datasets of three, ongoing phase 1 or 2 clinical trials (ALKA-372-001, STARTRK-1, and STARTRK-2), which enrolled patients aged 18 years or older with metastatic or locally advanced NTRK fusion-positive solid tumours who received entrectinib orally at a dose of at least 600 mg once per day in a capsule. All patients had an Eastern Cooperative Oncology Group performance status of 0-2 and could have received previous anti-cancer therapy (except previous TRK inhibitors). The primary endpoints, the proportion of patients with an objective response and median duration of response, were evaluated by blinded independent central review in the efficacy-evaluable population (ie, patients with NTRK fusion-positive solid tumours who were TRK inhibitor-naive and had received at least one dose of entrectinib). Overall safety evaluable population included patients from STARTRK-1, STARTRK-2, ALKA-372-001, and STARTRK-NG (NCT02650401; treating young adult and paediatric patients [aged ≤21 years]), who received at least one dose of entrectinib, regardless of tumour type or gene rearrangement. NTRK fusion-positive safety evaluable population comprised all patients who have received at least one dose of entrectinib regardless of dose or follow-up. These ongoing studies are registered with ClinicalTrials.gov, NCT02097810 (STARTRK-1) and NCT02568267 (STARTRK-2), and EudraCT, 2012-000148-88 (ALKA-372-001).FindingsPatients were enrolled in ALKA-372-001 from

Details

Database :
OAIster
Journal :
The Lancet. Oncology; vol 21, iss 2, 271-282; 1470-2045
Notes :
application/pdf, The Lancet. Oncology vol 21, iss 2, 271-282 1470-2045
Publication Type :
Electronic Resource
Accession number :
edsoai.on1391592609
Document Type :
Electronic Resource