Trial of Brigatinib After Treatment With Next-Generation ALK Inhibitors

  • End date
    Jan 24, 2022
  • participants needed
  • sponsor
    Criterium, Inc.
Updated on 24 January 2021
measurable disease
kinase inhibitor
serum bilirubin level
progressive disease
neutrophil count
cancer chemotherapy
stage iv non-small cell lung cancer
lung carcinoma
secondary malignant neoplasm of liver


The purpose of this study is to evaluate the safety and effectiveness of this investigational drug, brigatinib (AP261136) in patients with advanced non-small cell lung cancer Non-small cell lung cancer (NSCLC) who have had first-line treatment for their cancer and it still got worse, even after, or while taking drugs called ALK inhibitors, or anti-cancer drugs that act on tumors. Some examples of these anti-cancer drugs are: KEYTRUDA or ALECENSA).


A significant population of Anaplastic Lymphoma Kinase (ALK) plus Non-small cell lung cancer patients exist that have progressed on or who were intolerant of second generation anaplastic lymphoma kinase inhibitor (e.g. ceritinib or alectinib). Brigatinib has demonstrated activity in patients who have progressed on crizotinib, but the activity of brigatinib in patients who have progressed on ceritinib, alectinib, or other second generation anaplastic lymphoma kinase inhibitors is unknown. Based on the preclinical data. 3, , brigatinib has activity against known secondary anaplastic lymphoma kinase mutations suggesting it may retain activity after second-generation anaplastic lymphoma kinase inhibitors.

Patients enrolled in ARI-AT-002 must have previously received a second generation Anaplastic lymphoma kinase inhibitor other than brigatinib. We have chosen 20% as a clinically meaningful response rate that would justify further study of brigatinib in previously treated anaplastic lymphoma kinase plus disease.

Condition Non-Small Cell Lung Cancer, nsclc
Treatment brigatinib
Clinical Study IdentifierNCT02706626
SponsorCriterium, Inc.
Last Modified on24 January 2021


Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have Non-Small Cell Lung Cancer?
Do you have any of these conditions: nsclc or Non-Small Cell Lung Cancer?
Locally advanced or metastatic NSCLC that has been cytologically or
histologically confirmed
ALK rearrangement based on FDA approved test (e.g. Vysis breakapart FISH or
IHC using Ventana)
Age of 18 years
Brain lesions may be used as target lesions if progressing, 10mm in longest
diameter and if they were not previously treated with any of the following
Whole brain radiation therapy (WBRT) within 3 months
Stereotactic radiosurgery (SRS)
Surgical resection Availability of core biopsy of progressive lesion taken within 60 days prior to D1 of treatment under study therapy or willing to undergo tumor biopsy: NOTE:. All subjects must consent to provide tumor blocks or slides
If archival tissue is not available and biopsies to obtain fresh tumor tissue cannot be performed with minimal risk to the subject, subjects may be permitted to enroll on the study with prior approval of the Study PI
In the situation the patient undergoes biopsy within 60 days prior to D1. and there is insufficient tumor tissue subjects for the correlative science part of the protocol patient will be permitted to enroll on the study with prior approval of the study PI
In the situation the patient undergoes molecular testing or next-generation sequencing as part of standard care there must be sufficient tumor sample available for participation in the study (i.e. a next generation sequencing report is not sufficient for enrollment)
Recovered from toxicities related to prior anticancer treatment to Grade 2 or
baseline with the exception of alopecia
Have normal QT interval on ECG evaluation QT corrected Fridericia (QTcF) of
ms in males or 470 ms in females
Adequate organ function defined as
Absolute neutrophil count (ANC) 1500/L Platelets 75,000/L Hemoglobin 10g/dL
AST /ALT 2.5 x upper limit of normal (ULN); 5 x ULN if liver metastasis Total
serum bilirubin 1.5 x ULN Serum creatinine 1.5 x UNL Serum amylase 1.5 x UNL
At least 1 measurable lesion per RECIST version 1.1
Negative serum pregnancy test within 7 days of D1 of treatment in women of
child bearing potential (WOCBP)
If fertile, willing to use highly effective form of contraception (defined as
a combination of at least two of the following methods: condom or other
barrier methods, oral contraceptives, implantable contraceptives, intrauterine
devices) during the dosing period and for at least 4 months after
Ability to provide signed informed consent and willing and able to comply with
all study requirements
Inclusion criteria for cohort assignment
Cohort A: Progressive disease on any next generation ALK inhibitor except
first line alectinib or brigatinib (any line)
Cohort B: Progressive disease on first-line therapy with alectinib, and no
other ALK inhibitors
Cohort C: Previous treatment brigatinib at 180 mg daily for 4 weeks without >
grade 2 drug-related toxicities and with radiographic evidence of progressive
disease and no intervening systemic therapies such as chemotherapy
immunotherapy or another ALK inhibitor (radiation therapy allowed as
intervening therapy). Patients who are treated on cohorts A and B will be

Exclusion Criteria

Exclusion Criteria for cohorts A, B, and C
Patients meeting any of the following exclusion criteria will not be able to
participate in this study
History or the presence of pulmonary interstitial disease, drug-related or
immune-related pneumonitis, or radiation pneumonitis requiring medical
management within 6 months of trial enrollment
Prior treatment with brigatinib for cohorts A and B
History of or active significant gastrointestinal (GI) bleeding within 3
Malabsorption syndrome or other GI illness that could affect oral absorption
of the study drug
Received cytotoxic chemotherapy, investigational agents or radiation within 7
days prior to D1 of study treatment
Received prior ALK TKI therapy within 7 days prior to D1 of treatment under
study drug. 7 day wash out period is required after prior ALK inhibitor
Have significant, uncontrolled, or active cardiovascular disease, specifically
including, but not restricted to
Myocardial infarction (MI) within 6 months of trial enrollment
Unstable angina within 6 months of trial enrollment
Congestive heart failure (CHF) with 6 months prior to trial enrollment
Any history of ventricular arrhythmia
Cerebrovascular accident or transient ischemic attack within 6 months of D1 of study treatment
Clinically significant atrial arrhythmia or severe baseline bradycardia defined as resting heart rate < 60 beat per minute
Uncontrolled hypertension defined as baseline SBP> 160 and DBP > 100 on 3 separate clinic visits or past history of hypertensive urgency, emergency or encephalopathy
Have been diagnosed with another primary malignancy within the past 3 years
(except for adequately treated non-melanoma skin cancer, cervical cancer in
situ, or prostate cancer, which are allowed within 3 years)
Have symptomatic CNS metastases which require an increasing dose of
corticosteroids within the last 2 weeks to remain asymptomatic
Have active infection requiring intravenous antibiotics
Pregnant or breastfeeding
Have any condition or illness that, in the opinion of the investigator, would
compromise patient safety or interfere with evaluation of the study drug
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