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
Therapy
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

Abstract

Background

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.

Methods

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.

Results

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%).

Conclusions

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

rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn
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)
rn

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

rna

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

rnb

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

rn

Clinical trial identification

NCT01449461 and NCT02094573

Legal entity responsible for the study

ARIAD Pharmaceuticals, Inc.

Funding

ARIAD Pharmaceuticals, Inc.

Disclosure

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.