87O - Brigatinib in ALK+ NSCLC pts with intracranial CNS metastases in 2 clinical trials

Date 06 May 2017
Event ELCC 2017
Session Targeted therapies and management of brain metastasis
Topics Immunotherapy
Thoracic Malignancies
Non-Small Cell Lung Cancer
Presenter Marcello Tiseo
Citation Annals of Oncology (2017) 28 (suppl_2): ii28-ii51. 10.1093/annonc/mdx091
Authors M. Tiseo1, R.M. Huber2, M.J. Hochmair3, L.A. Bazhenova4, S.I. Ou5, W. Reichmann6, J. Haney6, D. Kerstein6, D.R. Camidge7, S.N. Gettinger8
  • 1Medical Oncology Unit, University Hospital of Parma, 41100 - Parma/IT
  • 2University Hospital of Munich, Munich/DE
  • 3Otto Wagner Hospital, Vienna/AT
  • 4University of California San Diego Moores Cancer Center, La Jolla/US
  • 5UC Irvine Health Chao Family Comprehensive Cancer Center, Orange/US
  • 6ARIAD Pharmaceuticals Inc., Cambridge/US
  • 7University of Colorado Cancer Center Anschutz Cancer Pavilion, Aurora/US
  • 8Yale Cancer Center, New Haven/US



The investigational next-generation anaplastic lymphoma kinase (ALK) inhibitor brigatinib is being evaluated in patients (pts) with ALK-positive non–small cell lung cancer (ALK+ NSCLC) in a phase 1/2 trial (Ph1/2) and a pivotal phase 2 trial (ALTA); most of these pts had intracranial central nervous system (CNS) metastases at baseline.


In Ph1/2 (NCT01449461), pts with advanced malignancies, including ALK+ NSCLC, received brigatinib (30–300 mg/d). In ALTA (NCT02094573), crizotinib-resistant pts with advanced ALK+ NSCLC received brigatinib at 90 mg qd in arm A or 180 mg qd with a 7-day lead-in at 90 mg in arm B. ALK+ NSCLC pts with baseline brain metastases were analyzed. CNS efficacy in both trials and safety in ALTA are shown.


In Ph1/2 and ALTA, 50/79 (63%) and 154/222 (69%) ALK+ NSCLC pts had baseline brain metastases based on independent review committee (IRC) and investigator assessment, respectively. Most pts had received chemotherapy (Table). In Ph1/2, 25/50 (50%) pts were receiving brigatinib as of 16 November 2015; in ALTA, 101/154 (66%) pts were receiving brigatinib as of 29 February 2016. In pts with measurable brain lesions, confirmed intracranial objective response rate was 53% in Ph1/2 and 42%/67% in ALTA A/B (Table). In pts with only nonmeasurable brain lesions, 35% (11/31) in Ph1/2 and 7% (4/54)/18% (10/55) in ALTA A/B had confirmed complete resolution of brain lesions. Further data are shown in the table. The most common treatment-emergent adverse events (TEAEs) in the 151 treated ALTA pts with baseline brain metastases were nausea (A/B, 32%/43%), headache (30%/30%), diarrhea (18%/36%), cough (21%/30%), and vomiting (25%/26%); the most common grade ≥3 TEAEs were increased blood creatine phosphokinase (1%/11%), hypertension (4%/7%), increased lipase (3%/3%), and pneumonia (1%/4%).


Brigatinib yielded substantial clinical activity in ALK+ NSCLC pts with brain metastases in 2 trials.rnTable: 87O

Baseline characteristics and IRC-assessed intracranial efficacy of brigatinib in ALK+ NSCLC Pts with brain metastases at baseline

rnPh1/2 n = 50ALTA Arm A n = 80ALTA Arm B n = 74
Median age, years534955
Received prior chemotherapy, %767476
Crizotinib-naive, %800
Pts evaluable for intracranial efficacy by IRC, na468073
Median iPFS, months14.615.612.8
Pts with measurable brain lesions, n152618
iORR, n (%)8 (53)11 (42)12 (67)
iDCR, n (%)13 (87)22 (85)15 (83)
No rad/activeb subset, n91915
iORR, n (%)6 (67)8 (42)11 (73)
iDCR, n (%)8 (89)16 (84)14 (93)

iDCR = intracranial disease control rate, iORR = intracranial objective response rate (confirmed), iPFS = intracranial progression-free survival


Last scan date: 8 October 2015 in Ph1/2; 14 April 2016 in ALTA


No prior brain radiotherapy in Ph1/2; active (untreated or treated and progressed) brain lesions in ALTA


Clinical trial identification

NCT01449461 and NCT02094573

Legal entity responsible for the study

ARIAD Pharmaceuticals, Inc.


ARIAD Pharmaceuticals, Inc.


M. Tiseo: Consulting or advisory role (AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Novartis, Otsuka, Pierre Fabre), research funding (ARIAD). R.M. Huber: Honoraria (ARIAD, AstraZeneca, BMS, Boehringer Ingelheim, Pfizer, Roche), consulting or advisory role (BMS, Boehringer Ingelheim, Celgene, Clovis Oncology, Eli Lilly, Novartis, Roche), research funding (Pierre Fabre). L.A. Bazhenova: Stock and other ownership interests (Epic Sciences), honoraria (Novartis), consulting or advisory role (AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Clovis Oncology, Genoptix, Heat Biologics, Pfizer, Roche/Genentech, Seattle Genetics, Trovagene), speakers bureau (AstraZeneca, Novartis, Pfizer, Roche/Genentech), research funding (AbbVie, ARIAD, Astellas, Astex, AstraZeneca/MedImmune, Boehringer Ingelheim, Chugai, Clovis Oncology, Eisai, Eli Lilly, Heat Biologics, Johnson & Johnson, Merck, Mirati, NanoCarrier, Novartis, Pfizer, Roche/Genentech). S-H.I. Ou: Advisory board (ARIAD). W. Reichmann, J. Haney, D. Kerstein: Employment, stock and other ownership interests (ARIAD). D.R. Camidge: Honoraria (ARIAD), research funding (ARIAD). S.N. Gettinger: Consulting or advisory role (ARIAD, BMS, Janssen), research funding (ARIAD, AstraZeneca/MedImmune, BMS, Boehringer Ingelheim, Incyte, Pfizer, Roche/Genentech). All other authors have declared no conflicts of interest.