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Poster display session

1423 - Brigatinib (BRG) in Anaplastic Lymphoma Kinase (ALK)–Positive Non–Small Cell Lung Cancer (NSCLC): Long-term Efficacy and Safety Results From a Phase 1/2 Trial

Date

09 Sep 2017

Session

Poster display session

Presenters

Lyudmila Bazhenova

Citation

Annals of Oncology (2017) 28 (suppl_5): v460-v496. 10.1093/annonc/mdx380

Authors

L.A. Bazhenova1, S.N. Gettinger2, C.J. Langer3, R. Salgia4, K.A. Gold5, R. Rosell6, A.T. Shaw7, G.J. Weiss8, J. Haney9, V.M. Rivera10, D. Kerstein11, R. Camidge12

Author affiliations

  • 1 Department Of Medicine, Moores Cancer Center, University of California San Diego, 92093 - La Jolla/US
  • 2 Yale Cancer Center, Yale School of Medicine, New Haven/US
  • 3 Abramson Cancer Center, University of Pennsylvania, Philadelphia/US
  • 4 Department Of Medical Oncology And Therapeutics Research, City of Hope, duarte/US
  • 5 Moores Cancer Center, University of California San Diego, La Jolla/US
  • 6 Germans Trias I Pujol Health Sciences Institute And Hospital, Catalan Institute of Oncology (ICO Badalona), Badalona/ES
  • 7 Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston/US
  • 8 Clinical Research, Cancer Treatment Centers of America, Goodyear/US
  • 9 Biomedical Data Sciences And Information, ARIAD Pharmaceuticals Inc., Cambridge/US
  • 10 Preclinical And Translational Research, ARIAD Pharmaceuticals Inc., Cambridge/US
  • 11 Clinical Research, ARIAD Pharmaceuticals Inc., Cambridge/US
  • 12 Cancer Center, University of Colorado, Aurora/US
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Resources

Abstract 1423

Background

The next-generation ALK inhibitor BRG has shown activity in ALK+ NSCLC patients (pts) in clinical trials.

Methods

Pts with advanced malignancies (N = 137; including 79 pts with ALK+ NSCLC) received oral BRG (30–300 mg/d) in a phase 1/2, open-label, multicenter trial (NCT01449461). We report activity by RECIST v1.1 in ALK+ NSCLC pts and safety in all pts, with long-term follow-up (>31 months since last pt was enrolled).

Results

Among 79 ALK+ NSCLC pts, median age was 54 years; 90% (71/79) had received prior crizotinib (CRZ). As of 21 Feb 2017, 32% of ALK+ NSCLC pts (25/79) and 25% (7/28) of those receiving 180 mg qd with a 7-day lead-in at 90 mg (a regimen evaluated in the phase 2 portion of the trial) continued to receive BRG. Median treatment duration was 20.0 months (1 day to 56.1 months). Confirmed objective response rate (ORR) was 63% (45/71) in pts with prior CRZ and 100% (8/8) in CRZ-naive pts. Additional efficacy data are shown in the table. At 180 mg qd (with lead-in), confirmed ORR was 76% (95% CI, 55%–91%) and median progression-free survival (PFS) was 16.3 months (95% CI, 9.2–28.1) in pts with prior CRZ. Treatment-emergent adverse events (AEs) in ≥ 30% of all 137 pts, mostly grade 1/2, were nausea (55%), fatigue (45%), diarrhea (42%), headache (36%), and cough (34%). Grade ≥3 treatment-emergent AEs in ≥ 5% of pts were increased lipase (12%), pneumonia (7%), dyspnea (6%), and hypertension (6%). Eleven percent of pts (15/137) discontinued BRG due to an AE.

Conclusions

BRG shows major antitumor activity in ALK+ NSCLC pts with an acceptable safety profile in this long-term follow-up. PFS of > 16 months in pts receiving 180 mg qd with a 7-day lead-in at 90 mg is among the longest reported in CRZ-resistant ALK+ NSCLC. This dosing regimen is being investigated in a randomized phase 3 trial of BRG vs CRZ in ALK inhibitor–naive pts with advanced ALK+ NSCLC (ALTA-1L; currently recruiting pts).Table:

1344P

Efficacy in ALK+ NSCLC Pts
With Prior CRZCRZ-Naive
All n = 7190 mg qdan = 1390 mg → 180 mg qda,b n = 25All n = 8
cORR, n (%) 95% CI45 (63) 51–757 (54) 25–8119 (76) 55–918 (100) 63–100
Median duration of response in confirmed responders, months 95% CI14.5 9.0–26.111.1 3.8–16.714.9 7.9–33.332.4 5.6–NR
Median PFS, months 95% CI13.2 9.2–16.711.9 3.5–21.216.3 9.2–28.134.2 7.4–NR
Probability of PFS at 1 year, % 95% CI53 41–6550 21–7462 40–7875 32–93
Median OS, months 95% CI30.1 21.4–NR21.2 9.9–47.629.5 21.4–NRNR NR–NR
Probability of OS at 1 year, % 95% CI77 65–8569 37–8784 63–94100 100–100
Probability of OS at 2 years, % 95% CI61 48–7146 19–7064 42–79100 100–100

Time-to-event data reflect Kaplan-Meier estimates ALK+ NSCLC, anaplastic lymphoma kinase–positive non–small cell lung cancer; BRG, brigatinib; CI, confidence interval; cORR, confirmed objective response rate; CRZ, crizotinib; NR, not reached; OS, overall survival; PFS, progression-free survival; pts, patients

a

BRG regimens used in the pivotal phase 2 trial

b

180 mg qd with 7-day lead-in at 90 mg.

Clinical trial identification

NCT01449461. First received by ClinicalTrials.gov: September 30, 2011

Legal entity responsible for the study

ARIAD Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

Funding

ARIAD Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

Disclosure

L.A. Bazhenova: Stock and other ownership interests (Epic Sciences), consulting or advisory role (AbbVie, ARIAD, AstraZeneca, Genoptix, Heat Biologics, Novartis, Pfizer, Trovagene), speakers bureau (AstraZeneca, Novartis, Roche/Genentech), research funding (BeyondSpring). S.N. Gettinger: Consulting or advisory role (ARIAD, BMS, Janssen), research funding (ARIAD, AstraZeneca/MedImmune, BMS, Boehringer Ingelheim, Incyte, Pfizer, Roche/Genentech). C.J. Langer: Honoraria (BMS, Eli Lilly/ImClone, Roche/Genentech), consulting or advisory role (Abbott, ARIAD, Bayer/Onyx, BMS, Cancer Support Community, Celgene, Clarient, Clovis Oncology, Eli Lilly/ImClone, Merck, Roche/Genentech), research funding (Advantagene, ARIAD, Celgene, Clovis Oncology, GSK, Inovio, Merck, Roche/Genentech, Stem CentRx). K.A. Gold: Honoraria (Roche/Genentech), consulting or advisory role (ARIAD), travel, accommodations, expenses (AstraZeneca), research funding (ARIAD, Astellas, AstraZeneca, BMS, Pharmacyclics, Roche/Genentech). A.T. Shaw: Honoraria (Novartis, Pfizer, Roche/Genentech), consulting or advisory role (ARIAD, Blueprint Medicines, Daiichi Sankyo, EMD Serono, Ignyta, Novartis, Pfizer, Roche/Genentech, Taiho), research funding (Novartis, Pfizer, Roche/Genentech). G.J. Weiss: Employment (Cancer Treatment Centers of America), consulting or advisory role (Blend Therapeutics, Paradigm, Pharmatech), speakers bureau (Amgen, Celgene, Medscape, Pfizer, Quintiles), travel, accommodations, expenses (Cambridge Healthtech Institute, Pharmatech), patents, royalties, other intellectual property (US Patent #8,911,940 issued 2014). J. Haney: Employment, stock and other ownership interests (ARIAD). V.M. Rivera, D. Kerstein: Employment, stock and other ownership interests (ARIAD). R. Camidge: Honoraria (ARIAD), research funding (ARIAD). All other authors have declared no conflicts of interest.

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