SAFETY PROFILE

Adverse Reactions in ≥10% (All Gradesa) or ≥2% (Grades 3-4) of Patients by Arm in ALTA 1L (N=273)

Adverse Reactions ALUNBRIG
(n=136)
crizotinib
(n=137)
  All Grades
(%)
Grades 3-4
(%)
All Grades
(%)
Grades 3-4
(%)
Gastrointestinal Disorders
Diarrhea 53 2.2 57 2.9
Nausea 30 2.2 58 2.9
Abdominal painb 24 0.7 33 3.6
Vomiting 21 0.7 44 2.2
Constipation 18 0 42 0
Stomatitisc 13 0.7 8.8 0
Dyspepsia 8 0 16 0.7
Gastroesophageal reflux disease 0.7 0 11 0
Skin and Subcutaneous Tissue Disorders
Rashd 40 2.9 17 0
Prurituse 20 0.7 5.8 0.7
Respiratory, Thoracic and Mediastinal Disorders
Cough 35 0 20 0
Dyspneaf 25 2.9 22r 3.6
ILD/Pneumonitis 5.1 2.9 2.2 0.7
Pulmonary embolism 2.2 2.2 5.8r 2.9
Vascular Disorders
Hypertensiong 32 13 8 2.9
General Disorders and Administration Site Conditions
Fatigueh 32 1.5 40 2.2
Edemai 18 0.7 48 0.7
Pyrexia 15 0.7 15 0
Musculoskeletal and Connective Tissue Disorders
Myalgiaj 28 0 23 0
Back pain 21 0.7 17 1.5
Arthralgia 14 0 12 0
Pain in extremity 5.1 0 15 0.7
Nervous System Disorders
Headachek 22 2.2 17 0
Dizziness 15 0.7 20 0.7
Peripheral neuropathyl 11 0.7 18 0
Dysgeusia 2.9 0 14 0
Investigations
Increased blood cholesterolm 13 0 0.7 0
Cardiac Disorders
Bradycardian 12 0.7 23 0
Infections and Infestations
Pneumoniao 15r 5.1 6.6r 2.9
Upper respiratory tract infectionp 12 0 10 0
Nasopharyngitis 8 0 11 0
Urinary tract infection 5.9 0.7 8.8 2.2
Metabolism and Nutrition Disorders
Decreased appetite 8.8 0.7 19 2.9
Eye Disorders
Visual disturbanceq 7.4 0 53 0.7

aPer National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

bIncludes abdominal discomfort, abdominal distension, abdominal pain, abdominal pain lower, abdominal pain upper, and epigastric discomfort.

cIncludes aphthous ulcer, mouth ulceration, oral mucosal blistering and stomatitis.

dIncludes dermatitis, dermatitis acneiform, dermatitis bullous, dermatitis contact, drug eruption, erythema, palmar-plantar erythrodysesthesia syndrome, rash, rash erythematous, rash macular, rash maculo-papular, rash papular, rash pruritic, rash pustular, toxic skin eruption, urticaria.

eIncludes pruritus, allergic pruritus, and generalized pruritus.

fIncludes dyspnea and exertional dyspnea.

gIncludes hypertension and systolic hypertension.

hIncludes asthenia and fatigue.

iIncludes angioedema, eye swelling, eyelid edema, face edema, generalized edema, lip swelling, peripheral edema, periorbital edema, peripheral swelling, skin swelling, swelling and swelling face.

jIncludes muscle spasms, muscle twitching, musculoskeletal discomfort, musculoskeletal pain, and myalgia.

kIncludes headache and migraine.

lIncludes burning sensation, dysesthesia, hyperesthesia, hypoesthesia, neuralgia, peripheral neuropathy, paraesthesia, peripheral sensory neuropathy and polyneuropathy.

mIncludes blood cholesterol increased, hypercholesterolemia.

nIncludes bradycardia, heart rate decreased, sinus bradycardia.

oIncludes lower respiratory tract infection, lung infection, pneumonia, aspiration pneumonia, and cryptococcal pneumonia.

pIncludes upper respiratory tract infection and viral upper respiratory tract infection.

qIncludes cataract, glaucoma, hypermetropia, night blindness, papilloedema, photophobia, photopsia, blurred vision, reduced visual acuity, visual field defect, visual impairment, and vitreous floaters.

rIncludes Grade 5 events.

Laboratory Abnormalities in ≥20% (All Gradesa) of Patients by Arm in ALTA 1L (N=273)

Laboratory Abnormality ALUNBRIG
(n=136)b
crizotinib
(n=137)b
  All Grades
(%)
Grades 3-4
(%)
All Grades
(%)
Grades 3-4
(%)
Chemistry
Increased creatine phosphokinase 81 24 68 4.8
Increased aspartate aminotransferase 72 4.5 70 5.2
Increased lipase 59 17 36 9.8
Hyperglycemiac 56 7.5 37 3.7
Increased alanine aminotransferase 52 5.2 77 13
Increased amylase 52 6.8 25 3
Decreased phosphorous 41 3.7 39 6
Increased alkaline phosphatase 36 3 49 1.5
Increased creatinine 25 0 33 0
Potassium increased 24 1.5 31 3.7
Increased calcium 22 0 1.5 0
Decreased magnesium 21 0 6.9 0
Decreased albumin 15 0.8 52 3.7
Decreased calcium 15 0 67 1.5
Hematology
Hemoglobin decreased 41 2.3 36 1.5
Lymphocyte count decreased 42 9.3 30 5.4
Neutrophil count decreased 12 0 34 6.8

aPer NCI CTCAE v4.0.

bDenominator for each laboratory parameter may vary and is defined as the number of patients who had both baseline and post-baseline test.

cElevated blood insulin was also observed in both arms.

Serious adverse reactions occurred in 33% of patients receiving ALUNBRIG® (brigatinib). The most common serious adverse reactions were pneumonia (4.4%), ILD/pneumonitis (3.7%), pyrexia (2.9%), dyspnea (2.2%), pulmonary embolism (2.2%), and asthenia (2.2%). Fatal adverse reactions occurred in 2.9% of patients and included pneumonia (1.5%), cerebrovascular accident (0.7%), and multiple organ dysfunction syndrome (0.7%).

In ALTA 1L, 13% of patients receiving ALUNBRIG permanently discontinued ALUNBRIG for adverse reactions. The most frequent adverse reactions that led to discontinuation were ILD/pneumonitis (3.7%) and pneumonia (2.2%).

In ALTA 1L, 38% of patients required a dose reduction due to adverse reactions. The most common adverse reaction that led to dose reduction was increased creatine phosphokinase (15%), increased lipase (6.6%), increased amylase (4.4%), increased aspartate aminotransferase (2.2%), ILD/pneumonitis (2.2%) and hypertension (2.2%).

The median duration of treatment with ALUNBRIG was 24.3 months.
The median relative dose intensity was 97% for ALUNBRIG.

Interstitial lung disease/pneumonitis

  • In the first-line phase 3 trial (ALTA 1L): ILD/pneumonitis occurred in 5.1% of patients receiving ALUNBRIG. ILD/pneumonitis occurred within 8 days of initiation of ALUNBRIG in 2.9% of patients, with Grade 3 to 4 reactions occurring in 2.2% of patients
  • In the post-crizotinib phase 2 trial (ALTA): ILD/pneumonitis occurred in 9.1% of patients. Adverse reactions consistent with possible ILD/pneumonitis occurred within 9 days of initiation of ALUNBRIG (median onset was 2 days) in 6.4% of patients, with Grade 3 to 4 reactions occurring in 2.7%

 

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In Vitro: ALUNBRIG Inhibited 17
ALK-Inhibitor—Resistant Mutations1,2

ALUNBRIG exhibited in vivo antitumor activity against 4 mutant forms of EML4-ALK, including the G1202R and L1196M mutants identified in NSCLC tumors in patients who had progressed on crizotinib.


 
 

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