133O - Brigatinib efficacy and safety in patients (Pts) with anaplastic lymphoma kinase (ALK)-positive (ALK+) non-small cell lung cancer (NSCLC) in a phas...

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session NSCLC targeted therapy and circulating biomarkers
Topics Cytotoxic agents
Non-small-cell lung cancer
Therapy
Biological therapy
Presenter Rafael Rosell
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors R. Rosell1, S.N. Gettinger2, L.A. Bazhenova3, C.J. Langer4, R. Salgia5, A.T. Shaw6, N.I. Narasimhan7, D.J. Dorer8, D. Kerstein9, D.R. Camidge10
  • 1Medical Oncology Service, Catalan Institute of Oncology, Badalona, 08916 - Barcelona/ES
  • 2Thoracic Oncology Program, Yale University School of Medicine Medical Oncology, 06520-8032 - New Haven/US
  • 3Moores Cancer Center, University of California San Diego, 92093 - La Jolla/US
  • 4Abramson Cancer Center, University of Pennsylvania, 19104 - Philadelphia/US
  • 5Thoracic Oncology, University of Chicago, 60637 - Chicago/US
  • 6Hematology/oncology, Massachusetts General Hospital, 02114-2696 - Boston/US
  • 7Drug Metabolism, Pharmacokinetics & Preclinical Safety, ARIAD Pharmaceuticals Inc., 02139 - Cambridge/US
  • 8Biostatics, ARIAD Pharmaceuticals Inc., 02139 - Cambridge/US
  • 9Clinical Research, ARIAD Pharmaceuticals Inc., 02139 - Cambridge/US
  • 10Thoracic Oncology, University of Colorado Cancer Center, 80045 - Aurora/US

Abstract

Background

Brigatinib is an investigational oral tyrosine kinase inhibitor with preclinical activity against the oncogenic ALK fusion protein and mutants resistant to crizotinib.

Methods

Pts with advanced malignancies received oral brigatinib (30–300 mg total daily) in this ongoing phase 1/2, single-arm, open-label, multicenter study (N = 137; NCT01449461). Efficacy (per RECIST v1.1) in ALK+ NSCLC pts and safety in all pts are reported.

Results

Among ALK+ NSCLC pts (n = 79), median age was 54 (29–83) years, 49% were female, and 90% had received crizotinib. As of February 17, 2015, 45/79 (57%) pts remained on study; median time on treatment was 12.6 months (1 day to 35.5 months). Evaluable ALK+ NSCLC pts with prior crizotinib (n = 70) had an objective response rate (ORR) of 71% and median progression-free survival (PFS) of 13.4 months (table). In a post hoc independent radiological review of pts with brain metastases at baseline, as of February 9, 2015: 8/15 (53%) pts with measurable (≥10 mm) brain lesions (including 5/9 [56%] pts with no prior brain radiotherapy) had an intracranial objective response; intracranial disease control rate was 87%. For all pts with an intracranial response (n = 19), median duration of intracranial response was 18.9 months. Treatment-emergent adverse events (TEAEs) in ≥30% of all 137 pts, mostly grades 1/2, were: nausea 52%; fatigue 42%; diarrhea 40%; headache 33%; cough 32%. Serious TEAEs (≥2% frequency; any cause) were: dyspnea 7%; pneumonia 6%; hypoxia 5%; pulmonary embolism 3%; pyrexia 2%. 133OT1 Table: Brigatinib efficacy in evaluable ALK+ NSCLC patients

EndpointPrior crizotinib (n = 70)Crizotinib-naive (n = 8)Total (n = 78)
Response, n (%)   
 ORR (CR + PR) [95% CI]50a (71) [59–82]8b (100) [63–100]58c (74) [63–84]
 CR4 (6)3 (38)7 (9)
 PR46 (66)5 (63)51 (65)
 SD11 (16)d011 (14)d
 PD6 (9)06 (8)
 Termination before scan3 (4)03 (4)
Median duration of response e,f, months9.9Not reached11.2
Median PFS e, months13.4Not reached13.4
CI, confidence interval; CR, complete response; ORR, objective response rate; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease.a Includes 43 confirmed responses. b Includes 7 confirmed responses. c Includes 50 confirmed responses. d Includes non-CR/non-PD for 4 pts with non-measurable disease only at baseline.e Kaplan–Meier estimate; f 55 pts were evaluable for duration of response, 48 with prior crizotinib and 7 crizotinib-naive.

Conclusions

Brigatinib showed antitumor activity in crizotinib-treated (71% ORR; median PFS, 13.4 months) and crizotinib-naive (100% ORR) ALK+ NSCLC pts, including pts with brain metastases at baseline (53% intracranial ORR in pts with measurable brain lesions). A pivotal, randomized, phase 2 trial of brigatinib in pts with crizotinib-resistant ALK+ NSCLC has completed accrual.

Clinical trial identification

NCT01449461

Legal entity responsible for the study

ARIAD Pharmaceuticals, Inc.

Funding

ARIAD Pharmaceuticals, Inc.

Disclosure

S.N. Gettinger: Consulting or advisory role (ARIAD, BMS, Janssen), research funding (ARIAD, AstraZeneca/MedImmune, Boehringer Ingelheim, BMS, Genentech, Incyte, Pfizer). L.A. Bazhenova: Stock and other ownership interests (Epic Sciences), honoraria (Novartis), consulting or advisory role (Boehringer Ingelheim, Clovis Oncology, Seattle Genetics), speakers bureau (Genentech, Pfizer), research funding (ARIAD, Astellas, Astex, AstraZeneca, Boehringer Ingelheim, Chugai, Eisai, Eli Lilly, Heat Biologics, Johnson & Johnson, MedImmune, Merck, Mirati, NanoCarrier, Novartis, Roche), travel, accommodations, expenses (Boehringer Ingelheim, Clovis Oncology, Genentech, Pfizer, Seattle Genetics). C.J. Langer: Honoraria (BMS, Genentech/Roche, Lilly/ImClone), consulting or advisory role (Abbott, AstraZeneca, Bayer/Onyx, Cancer Support Community, Celgene, Clarient, Clovis Oncology, Genentech/Roche, Lilly/ImClone, Merck, Millennium), research funding (Advantagene, ARIAD, BMS, Celgene, Clovis Oncology, Genentech/Roche, GSK, Inovio, Merck). A.T. Shaw: Honoraria (Novartis, Pfizer, Roche), consulting or advisory role (ARIAD, Blueprint Medicines, Daiichi Sankyo, EMD Serono, Genentech, Ignyta, Novartis, Pfizer, Roche, Taiho), research funding (ARIAD, Genentech, Novartis, Pfizer). N.I. Narasimhan, D.J. Dorer, D. Kerstein: Employment, stock and other ownership interests (ARIAD). D.R. Camidge: Honoraria, research funding (ARIAD). All other authors have declared no conflicts of interest.