U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C21H22F2N6O2
Molecular Weight 428.436
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LAROTRECTINIB

SMILES

C1C[C@]([H])(c2cc(ccc2F)F)N(C1)c3ccn4c(c(cn4)N=C(N5CC[C@@]([H])(C5)O)O)n3

InChI

InChIKey=NYNZQNWKBKUAII-KBXCAEBGSA-N
InChI=1S/C21H22F2N6O2/c22-13-3-4-16(23)15(10-13)18-2-1-7-28(18)19-6-9-29-20(26-19)17(11-24-29)25-21(31)27-8-5-14(30)12-27/h3-4,6,9-11,14,18,30H,1-2,5,7-8,12H2,(H,25,31)/t14-,18+/m0/s1

HIDE SMILES / InChI

Molecular Formula C21H22F2N6O2
Molecular Weight 428.436
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Larotrectinib (previously known as ARRY-470 and LOXO-101) is a potent, oral and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities involving the tropomyosin receptor kinases (TRKs). Larotrectinib is in phase II clinical trials for the treatment patients with solid tumors, non-Hodgkin lymphoma and for the pediatric patients with advanced solid or primary CNS tumors.

CNS Activity

Curator's Comment:: Known to be CNS non-penetrant in mouse. Human data not available

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
VITRAKVI

Approved Use

Vitrakvi is specifically indicated for the treatment of adult and pediatric patients with solid tumors that: • have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation, • are metastatic or where surgical resection is likely to result in severe morbidity, and • have no satisfactory alternative treatments or that have progressed following treatment.

Launch Date

1.54310397E12
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
788 ng/mL
100 mg 2 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
LAROTRECTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
4351 ng × h/mL
100 mg 2 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
LAROTRECTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.9 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LAROTRECTINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Disc. AE: Brain edema, Intestinal perforation...
Other AEs: Fatigue, Nausea...
AEs leading to
discontinuation/dose reduction:
Brain edema (1 - 2)
Intestinal perforation (1 - 2)
Pericardial effusion (1 - 2)
Pleural effusion (1 - 2)
Small intestinal obstruction (1 - 2)
Dehydration (1 - 2)
Fatigue (1 - 2)
ALT increased (1 - 2)
AST increased (1 - 2)
Enterocutaneous fistula (1 - 2)
Amylase increased (1 - 2)
Lipase increased (1 - 2)
Muscular weakness (1 - 2)
Abdominal pain (1 - 2)
Asthenia (1 - 2)
Decreased appetite (1 - 2)
Dyspnea (1 - 2)
Hyponatremia (1 - 2)
Jaundice (1 - 2)
Syncope (1 - 2)
Vomiting (1 - 2)
Nausea (1 - 2)
Acute myeloid leukemia (1 - 2)
Other AEs:
Fatigue (>20)
Nausea (>20)
Dizziness (>20)
Vomiting (>20)
Anemia (>20)
AST increased (>20)
Cough (>20)
ALT increased (>20)
Constipation (>20)
Diarrhea (>20)
ALT increased (6%)
AST increased (6%)
Dizziness (3%)
Sources: Page: 6.1
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Other AEs: Fatigue, Pyrexia...
Other AEs:
Fatigue (all grades, 37%)
Pyrexia (all grades, 18%)
Edema peripheral (all grades, 15%)
Nausea (all grades, 29%)
Vomiting (all grades, 26%)
Constipation (all grades, 23%)
Diarrhea (all grades, 22%)
Abdominal pain (all grades, 13%)
Dizziness (all grades, 28%)
Headache (all grades, 14%)
Cough (all grades, 26%)
Dyspnea (all grades, 18%)
Nasal congestion (all grades, 10%)
Fatigue (grade 3-4, 3%)
Pyrexia (grade 3-4, 1%)
Nausea (grade 3-4, 1%)
Vomiting (grade 3-4, 1%)
Constipation (grade 3-4, 1%)
Diarrhea (grade 3-4, 2%)
Abdominal pain (grade 3-4, 2%)
Dizziness (grade 3-4, 1%)
Dyspnea (grade 3-4, 2%)
Weight increased (all grades, 15%)
Arthralgia (all grades, 14%)
Myalgia (all grades, 14%)
Muscular weakness (all grades, 13%)
Back pain (all grades, 12%)
Pain in extremity (all grades, 12%)
Decreased appetite (all grades, 13%)
Decreased appetite (all grades, 11%)
Weight increased (grade 3-4, 4%)
Arthralgia (grade 3-4, 1%)
Myalgia (grade 3-4, 1%)
Back pain (grade 3-4, 1%)
Pain in extremity (grade 3-4, 1%)
Decreased appetite (grade 3-4, 2%)
Decreased appetite (grade 3-4, 2%)
Sources: Page: Table 2
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 3
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 3
Other AEs: ALT increased, AST increased...
Other AEs:
ALT increased (all grades, 45%)
AST increased (all grades, 45%)
Hypoalbuminemia (all grades, 35%)
Alkaline phosphatase increased (all grades, 30%)
Anemia (all grades, 42%)
Neutropenia (all grades, 23%)
ALT increased (grade 3-4, 3%)
AST increased (grade 3-4, 3%)
Hypoalbuminemia (grade 3-4, 2%)
Alkaline phosphatase increased (grade 3-4, 3%)
Anemia (grade 3-4, 10%)
Neutropenia (grade 3-4, 7%)
Sources: Page: Table 3
150 mg 2 times / day steady, oral
Higher than recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
unhealthy, adult
n = 7
Health Status: unhealthy
Condition: solid tumours
Age Group: adult
Sex: unknown
Population Size: 7
Sources:
DLT: Alanine aminotransferase increased, Aspartate aminotransferase increased...
Dose limiting toxicities:
Alanine aminotransferase increased (1 patient)
Aspartate aminotransferase increased (1 patient)
Sources:
200 mg 2 times / day steady, oral
Highest studied dose
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy, adult
n = 6
Health Status: unhealthy
Condition: solid tumours
Age Group: adult
Sex: unknown
Population Size: 6
Sources:
DLT: Dizziness...
Dose limiting toxicities:
Dizziness (1 patient)
Sources:
200 mg 2 times / day steady, oral
Highest studied dose
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources: Page: 91
unhealthy, adult
n = 6
Health Status: unhealthy
Condition: solid tumor
Age Group: adult
Sex: unknown
Population Size: 6
Sources: Page: 91
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
unhealthy, adult
n = 6
Health Status: unhealthy
Condition: solid tumours
Age Group: adult
Sex: unknown
Population Size: 6
Sources:
DLT: Dizziness...
Dose limiting toxicities:
Dizziness (1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
ALT increased 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
AST increased 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Abdominal pain 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Acute myeloid leukemia 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Amylase increased 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Asthenia 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Brain edema 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Decreased appetite 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Dehydration 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Dyspnea 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Enterocutaneous fistula 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Fatigue 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Hyponatremia 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Intestinal perforation 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Jaundice 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Lipase increased 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Muscular weakness 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Nausea 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Pericardial effusion 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Pleural effusion 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Small intestinal obstruction 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Syncope 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Vomiting 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Dizziness 3%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
ALT increased 6%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
AST increased 6%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
ALT increased >20
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
AST increased >20
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Anemia >20
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Constipation >20
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Cough >20
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Diarrhea >20
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Dizziness >20
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Fatigue >20
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Nausea >20
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Vomiting >20
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: 6.1
Nasal congestion all grades, 10%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Decreased appetite all grades, 11%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Back pain all grades, 12%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Pain in extremity all grades, 12%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Abdominal pain all grades, 13%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Decreased appetite all grades, 13%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Muscular weakness all grades, 13%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Arthralgia all grades, 14%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Headache all grades, 14%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Myalgia all grades, 14%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Edema peripheral all grades, 15%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Weight increased all grades, 15%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Dyspnea all grades, 18%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Pyrexia all grades, 18%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Diarrhea all grades, 22%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Constipation all grades, 23%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Cough all grades, 26%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Vomiting all grades, 26%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Dizziness all grades, 28%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Nausea all grades, 29%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Fatigue all grades, 37%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Arthralgia grade 3-4, 1%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Back pain grade 3-4, 1%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Constipation grade 3-4, 1%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Dizziness grade 3-4, 1%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Myalgia grade 3-4, 1%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Nausea grade 3-4, 1%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Pain in extremity grade 3-4, 1%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Pyrexia grade 3-4, 1%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Vomiting grade 3-4, 1%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Abdominal pain grade 3-4, 2%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Decreased appetite grade 3-4, 2%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Decreased appetite grade 3-4, 2%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Diarrhea grade 3-4, 2%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Dyspnea grade 3-4, 2%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Fatigue grade 3-4, 3%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Weight increased grade 3-4, 4%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 2
Neutropenia all grades, 23%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 3
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 3
Alkaline phosphatase increased all grades, 30%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 3
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 3
Hypoalbuminemia all grades, 35%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 3
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 3
Anemia all grades, 42%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 3
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 3
ALT increased all grades, 45%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 3
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 3
AST increased all grades, 45%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 3
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 3
Anemia grade 3-4, 10%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 3
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 3
Hypoalbuminemia grade 3-4, 2%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 3
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 3
ALT increased grade 3-4, 3%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 3
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 3
AST increased grade 3-4, 3%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 3
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 3
Alkaline phosphatase increased grade 3-4, 3%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 3
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 3
Neutropenia grade 3-4, 7%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources: Page: Table 3
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources: Page: Table 3
Alanine aminotransferase increased 1 patient
DLT
150 mg 2 times / day steady, oral
Higher than recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
unhealthy, adult
n = 7
Health Status: unhealthy
Condition: solid tumours
Age Group: adult
Sex: unknown
Population Size: 7
Sources:
Aspartate aminotransferase increased 1 patient
DLT
150 mg 2 times / day steady, oral
Higher than recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
unhealthy, adult
n = 7
Health Status: unhealthy
Condition: solid tumours
Age Group: adult
Sex: unknown
Population Size: 7
Sources:
Dizziness 1 patient
DLT
200 mg 2 times / day steady, oral
Highest studied dose
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy, adult
n = 6
Health Status: unhealthy
Condition: solid tumours
Age Group: adult
Sex: unknown
Population Size: 6
Sources:
Dizziness 1 patient
DLT
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
unhealthy, adult
n = 6
Health Status: unhealthy
Condition: solid tumours
Age Group: adult
Sex: unknown
Population Size: 6
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
yes
yes
yes (co-administration study)
Comment: larotrectinib increased midazolam both AUC and Cmax by 1.7-fold
Page: 94.0
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
yes [Km >300 uM]
yes [Km >300 uM]
yes (co-administration study)
Comment: rifampin increased larotrectinib AUC by 1.7-fold and Cmax by 1.8-fold
Page: 93, 94, 106
yes
yes (co-administration study)
Comment: coadministration with midazolam increased midazolam AUC and Cmax by 1.7-fold; itraconazole increased larotrectinib AUC by 4.3-fold and Cmax by 2.8-fold; rifampin decreased larotrectinib AUC by 81% and Cmax by 71%
Page: 95, 104, 105
Tox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer.
2013 Nov
An Oncogenic NTRK Fusion in a Patient with Soft-Tissue Sarcoma with Response to the Tropomyosin-Related Kinase Inhibitor LOXO-101.
2015 Oct
Targeting NTRK fusion in non-small cell lung cancer: rationale and clinical evidence.
2017 Jun
Rapid Response to Larotrectinib (LOXO-101) in an Adult Chemotherapy-Naive Patients With Advanced Triple-Negative Secretory Breast Cancer Expressing ETV6-NTRK3 Fusion.
2018 Jun

Sample Use Guides

Oral capsule of LOXO-101 (ARRY-470 (FREE BASE)) - 100mg BID
Route of Administration: Oral
ARRY-470 is a selective kinase inhibitor with nanomolar activity against TRKA/B/C but no other significant kinase inhibition below 1000nM. Treatment of cells expressing MPRIP- or CD74-NTRK1 with ARRY-470, CEP-701 and, to a lesser extent, crizotinib, inhibited autophosphorylation of RIP-TRKA and CD74-TRKA. It induces cell-cycle arrest in G1 and apoptosis of KM12 cells.
Substance Class Chemical
Created
by admin
on Sat Jun 26 06:58:44 UTC 2021
Edited
by admin
on Sat Jun 26 06:58:44 UTC 2021
Record UNII
PF9462I9HX
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LAROTRECTINIB
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
BAY-2757556
Code English
LOXO-101
Code English
ARRY-470
Code English
LAROTRECTINIB [USAN]
Common Name English
LAROTRECTINIB [WHO-DD]
Common Name English
1-PYRROLIDINECARBOXAMIDE, N-(5-((2R)-2-(2,5-DIFLUOROPHENYL)-1-PYRROLIDINYL)PYRAZOLO(1,5-A)PYRIMIDIN-3-YL)-3-HYDROXY-, (3S)-
Systematic Name English
LAROTRECTINIB [INN]
Common Name English
(3S)-N-(5-((2R)-2-(2,5-DIFLUOROPHENYL)PYRROLIDIN- 1-YL)PYRAZOLO(1,5-A)PYRIMIDIN-3-YL)-3-HYDROXYPYRROLIDINE- 1-CARBOXAMIDE
Systematic Name English
BAY2757556
Code English
Classification Tree Code System Code
NCI_THESAURUS C129825
Created by admin on Sat Jun 26 06:58:44 UTC 2021 , Edited by admin on Sat Jun 26 06:58:44 UTC 2021
NCI_THESAURUS C1967
Created by admin on Sat Jun 26 06:58:44 UTC 2021 , Edited by admin on Sat Jun 26 06:58:44 UTC 2021
EU-Orphan Drug EU/3/18/2098
Created by admin on Sat Jun 26 06:58:44 UTC 2021 , Edited by admin on Sat Jun 26 06:58:44 UTC 2021
FDA ORPHAN DRUG 578317
Created by admin on Sat Jun 26 06:58:44 UTC 2021 , Edited by admin on Sat Jun 26 06:58:44 UTC 2021
Code System Code Type Description
DRUG BANK
DB14723
Created by admin on Sat Jun 26 06:58:44 UTC 2021 , Edited by admin on Sat Jun 26 06:58:44 UTC 2021
PRIMARY
CAS
1223403-58-4
Created by admin on Sat Jun 26 06:58:44 UTC 2021 , Edited by admin on Sat Jun 26 06:58:44 UTC 2021
PRIMARY
MANUFACTURER PRODUCT INFORMATION
LOXO-101
Created by admin on Sat Jun 26 06:58:44 UTC 2021 , Edited by admin on Sat Jun 26 06:58:44 UTC 2021
PRIMARY MedKoo CAT NO: 206207CAS NO: 1223403-58-4Description: LOXO-101, also known as ARRY-470, is an orally bioavailable, potent, ATP-competitive inhibitor of TRKA, TRKB, and TRKC. LOXO-101 has IC50 values in the low nanomolar range for inhibition of all three TRK family members in binding and cellular assays, with 100x selectivity over other kinases, and has shown acceptable pharmaceutical properties and safety in nonclinical models. The TRK family of neurotrophin receptors, TRKA, TRKB, and TRKC (encoded by NTRK1, NTRK2, and NTRK3 genes, respectively) and their neurotrophin ligands regulate growth, differentiation and survival of neurons. (Last updated: 6/9/2016).
DRUG CENTRAL
5305
Created by admin on Sat Jun 26 06:58:44 UTC 2021 , Edited by admin on Sat Jun 26 06:58:44 UTC 2021
PRIMARY
NCI_THESAURUS
C115977
Created by admin on Sat Jun 26 06:58:44 UTC 2021 , Edited by admin on Sat Jun 26 06:58:44 UTC 2021
PRIMARY
FDA UNII
PF9462I9HX
Created by admin on Sat Jun 26 06:58:44 UTC 2021 , Edited by admin on Sat Jun 26 06:58:44 UTC 2021
PRIMARY
ChEMBL
CHEMBL3545075
Created by admin on Sat Jun 26 06:58:44 UTC 2021 , Edited by admin on Sat Jun 26 06:58:44 UTC 2021
PRIMARY
PUBCHEM
46188928
Created by admin on Sat Jun 26 06:58:44 UTC 2021 , Edited by admin on Sat Jun 26 06:58:44 UTC 2021
PRIMARY
RXCUI
2105628
Created by admin on Sat Jun 26 06:58:44 UTC 2021 , Edited by admin on Sat Jun 26 06:58:44 UTC 2021
PRIMARY
MANUFACTURER PRODUCT INFORMATION
ARRY 470
Created by admin on Sat Jun 26 06:58:44 UTC 2021 , Edited by admin on Sat Jun 26 06:58:44 UTC 2021
PRIMARY Biological Activity: LOXO-101 is an orally bioavailable, potent, ATP-competitive inhibitor of TRKA, TRKB, and TRKC. LOXO-101 has IC50 values in the low nanomolar range for inhibition of all three TRK family members in binding and cellular assays, with 100x selectivity over other kinases, and has shown acceptable pharmaceutical properties and safety in nonclinical models. The TRK family of neurotrophin receptors, TRKA, TRKB, and TRKC (encoded by NTRK1, NTRK2, and NTRK3 genes, respectively) and their neurotrophin ligands regulate growth, differentiation and survival of neurons. Translocations involving the TRK kinase domain, mutations involving the TRK ligand-binding site, amplifications of NTRK, TRK splice variants, and autocrine/paracrine signaling are described in diverse tumor types, and may contribute to tumorigenesis. LOXO-101 is currently being developed by Loxo Oncology, Inc.
INN
10360
Created by admin on Sat Jun 26 06:58:44 UTC 2021 , Edited by admin on Sat Jun 26 06:58:44 UTC 2021
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> INDUCER
TRANSPORTER -> SUBSTRATE
In overexpressing BCRP and P-gp cell line, the estimate Km for both transporters is >300 ?M.
TRANSPORTER -> SUBSTRATE
In overexpressing BCRP and P-gp cell line, the estimate Km for both transporters is >300 ?M. Coadministration of larotrectinib with a single dose of a P-gp inhibitor (rifampin), increased the AUCinf of larotrectinib by 1.7-fold and the Cmax by 1.8-fold as compared to larotrectinib administered alone.
EXCRETED UNCHANGED
Following oral administration of a single [14C] radiolabeled 100 mg dose of larotrectinib to healthy subjects, 58% (5% unchanged) of the administered radioactivity was recovered in feces and 39% (20% unchanged) was recovered in urine
FECAL; URINE
TARGET -> INHIBITOR
Active against NTRK gene fusions. Competitive to ATP binding site.
COMPETITIVE INHIBITOR
IC50
METABOLIC ENZYME -> SUBSTRATE
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
IC50
BINDER->LIGAND
METABOLIC ENZYME -> INHIBITOR
Coadministration of multiple doses of larotrectinib with a sensitive CYP3A4 substrate (midazolam) increased the AUCinf and Cmax of midazolam by 1.7-fold as compared to midazolam administered alone.
TARGET -> INHIBITOR
IC50
Related Record Type Details
ACTIVE MOIETY
LOXO-101 has IC50 values in the low nanomolar range for inhibition of all three TRK family members in binding and cellular assays, with 100x selectivity over other kinases, and has shown acceptable pharmaceutical properties and safety in preclinical models. LOXO-101 is an orally bioavailable, potent, ATP-competitive inhibitor of TRKA, TRKB, and TRKC. LOXO-101 has IC50 values in the low nanomolar range for inhibition of all three TRK family members in binding and cellular assays, with 100x selectivity over other kinases, and has shown acceptable pharmaceutical properties and safety in nonclinical models.
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC ORAL

DOSE

Volume of Distribution PHARMACOKINETIC DOSE

Tmax PHARMACOKINETIC BID