NSCLC: ALTA-1L trial

Abbreviations

No EU-CTR

  • ALTA-1L references
    2018-11-22
    D.R. Camidge
    Brigatinib versus Crizotinib in ALK-Positive Non–Small-Cell Lung Cancer
Investigated (inv)
Comparator (comp)

BRIG

CRIZ

137

138

Phase:

3

Randomisation:

Open label

Primary tumour:

NSCLC

Subtype (biomarker):

ALK poz.

Stage:

meta

Line of therapy:

L1

Primary
BRIG
CRIZ
HR
p
PFS @1yr
67%
43%
0.49 (0.33-0.74)
<0.001
Secondaries
BRIG
CRIZ
HR
p
ORR ITT
71%
60%
0.63 (0.38-1.04)
na
ORR intracranial
78%
29%
0.09 (0.02-0.52)
na
DoR @1yr
78%
48%
na
na
(all grades, %)
BRIG
CRIZ
p
Any AE grade ≥3
61%
55%
NA
Diarrhea
49%
55%
NA
Increased blood creatine kinase level
39%
15%
NA
Nausea
26%
56%
NA
Cough
25%
16%
NA
Hypertension
23%
7%
NA
Increased AST level
19%
32%
NA
Increased lipase level
19%
12%
NA
Vomiting
18%
39%
NA
Constipation
15%
42%
NA
Increased amylase level
14%
7%
NA
Pruritus
13%
4%
NA
Dysgeusia
4%
19%
NA
Increased blood creatinine level
2%
14%
  • Inclusion
  • Exclusion

- Have histologically or cytologically confirmed stage IIIB (and not a candidate for definitive multimodality therapy) or stage four (IV) NSCLC. - Must have documented ALK rearrangement. - Have sufficient tumor tissue available for central analysis. - Have at least 1 measurable (that is, target) lesion per RECIST v1.1. - Recovered from toxicities related to prior anticancer therapy to National Cancer Institute (of the United States) (NCI) Common Terminology Criteria for Adverse Events (version 4.0) (CTCAE v 4.0) grade be less than or equal to (<=) 1. - Are a male or female participants greater than or equal to (>=)18 years old. - Have adequate organ function, as defined by the study protocol. - Have Eastern Cooperative Oncology Group (ECOG) performance status <=2. - Have normal QT interval on screening ECG evaluation, defined as QT interval corrected (Fridericia) (QTcF) of <= 450 millisecond (msec) in males or <=470 msec in females. - For female participants of childbearing potential, have a negative pregnancy test documented prior to randomization. - For female and male participants who are fertile, agree to use a highly effective form of contraception, as defined by the study protocol. - Provide signed and dated informed consent indicating that the participants has been informed of all pertinent aspects of the study, including the potential risks, and is willingly participating. - Have the willingness and ability to comply with scheduled visit and study procedures.

- Previously received an investigational antineoplastic agent for NSCLC. - Previously received any prior tyrosine kinase inhibitor (TKI), including ALK-targeted TKIs. - Previously received more than 1 regimen of systemic anticancer therapy for locally advanced or metastatic disease. - Received chemotherapy or radiation within 14 days of first dose of study drug, except stereotactic radiosurgery (SRS) or stereotactic body radiation therapy (SBRT). - Received anti-neoplastic monoclonal antibodies within 30 days of the first dose of study drug. - Had major surgery within 30 days of the first dose of study drug, minor surgical procedures such as catheter placement or minimally invasive biopsies are allowed. - Have been diagnosed with another primary malignancy other than NSCLC, except for adequately treated non-melanoma skin cancer or cervical cancer in situ; definitively treated non-metastatic prostate cancer; or participants with another primary malignancy who are definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy. - Have symptomatic CNS metastases (parenchymal or leptomeningeal) at screening or asymptomatic disease requiring an increasing dose of corticosteroids to control symptoms within 7 days prior to randomization. - Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging). Participants with leptomeningeal disease and without cord compression are allowed. - Be pregnant, planning a pregnancy, or breastfeeding. - Have significant, uncontrolled, or active cardiovascular disease, as defined by the study protocol. - Have uncontrolled hypertension. - Have a history or the presence at baseline of pulmonary interstitial disease, drug-related pneumonitis, or radiation pneumonitis. - Have an ongoing or active infection. - Have a known history of human immunodeficiency virus (HIV) infection. - Have a known or suspected hypersensitivity to brigatinib or its excipients and/or crizotinib or its excipients. - Have malabsorption syndrome or other gastrointestinal (GI) illness or condition. - Have any condition or illness that, in the opinion of the investigator, would compromise participant's safety or interfere with the evaluation of the study drug.

Characteristics
BRIG
CRIZ
Agedc-comma sex
Median age (range) - no(%)
58 (27–86)
60 (29–89)
Female - no(%)
69 (50)
81 (59)
Race - no(%)
Non-Asian
78 (57)
89 (64)
Asian
59 (43)
49 (36)
ECOG performance-status score - no(%)
0 or 1
131 (96)
132 (96)
2
6 (4)
6 (4)
History of tobacco use - no(%)
Never smoked
84 (61)
75 (54)
Former smoker
49 (36)
56 (41)
Current smoker
4 (3)
7 (5)
Stage of disease at trial entry - no(%)
IIIB
8 (6)
12 (9)
IV
129 (94)
126 (91)
Histologic type - no(%)
Adenocarcinoma
126 (92)
137 (99)
Adenosquamous carcinoma
3 (2)
1 (1)
Squamous-cell carcinoma
4 (3)
0
Large-cell carcinoma
2 (1)
0
Other
ALK status assessed locally with the use of FDA-approved test
123 (90)
112 (81)
Brain metastases - no(%)
40 (29)
41 (30)
Previous radiotherapy to brain - no(%)
18 (13)
19 (14)
Previous chemo in pts with LA or Meta disease - no(%)
36 (26)
37 (27)
Ad-hoc:
no.pts inv.
no.pts comp.
BRIG
CRIZ
HR
p
  • PFS @1yr
analisys of PFS @1yr
BRIG
CRIZ
HR (95% CI)
Age
<65 yr
0.44 (0.26–0.74)
≥65 yr
0.59 (0.30–1.18)
Sex
Male
0.49 (0.28–0.85)
Female
0.44 (0.24–0.84)
Race
Non-Asian
0.54 (0.33–0.90)
Asian
0.41 (0.20–0.86)
History of tobacco use
Never smoked
0.47 (0.27–0.84)
Former smoker
0.51 (0.27–0.97)
ECOG performance-status score
0
0.19 (0.06–0.55)
1
0.60 (0.37–0.98)
Brain metastases at baseline
Yes
0.20 (0.09–0.46)
No
0.72 (0.44–1.18)
Previous chemotherapy
Yes
0.35 (0.14–0.85)
No
0.55 (0.34–0.88)
analisys of
BRIG
CRIZ
HR (95% CI)