GAVRETO was generally well tolerated1

Safety of GAVRETO was evaluated in 220 patients with RET+ mNSCLC in ARROW

  • The most common adverse reactions (≥25%) were fatigue, constipation, musculoskeletal pain, and hypertension
  • The most frequent serious adverse reaction (in ≥2% of patients) was pneumonia, pneumonitis, sepsis, urinary tract infection, and pyrexia
  • Fatal adverse reaction occurred in 5% of patients; fatal adverse reaction which occurred in >1 patient included pneumonia (n=3) and sepsis (n=2)
96.5% of patients did not discontinue GAVRETO due to treatment-related adverse reactions.2 of patients did not discontinue GAVRETO due to an adverse reaction.

Adverse reactions resulting in permanent discontinuation included pneumonitis (1.8%), pneumonia (1.8%), and sepsis (1%).

36%

Dose reductions due to adverse
reactions in GAVRETO-treated patients.

Adverse reactions requiring dosage reductions in ≥2% of patients included neutropenia, anemia, pneumonitis, neutrophil count decreased, fatigue, hypertension, pneumonia, and leukopenia.

60%

Dosage interruptions due to an adverse
reaction of GAVRETO-treated patients

Adverse reactions requiring dosage interruption in ≥2% of patients included neutropenia, pneumonitis, anemia, hypertension, pneumonia, pyrexia, increased aspartate aminotransferase (AST), increased blood creatine phosphokinase, fatigue, leukopenia, thrombocytopenia, vomiting, increased alanine aminotransferase (ALT), sepsis, and dyspnea.

Adverse reactions (≥15%) in patients who received GAVRETO in ARROW

Adverse Reactions GAVRETO N=220
Grades 1-4 (%) Grades 3-4 (%)
General
Fatigue 35 2.3**
Pyrexia 20 0
Edema 20 0
Gastrointestinal
Constipation 35 1**
Diarrhea 24 3.2**
Dry Mouth 16 0
Adverse Reactions (cont'd) GAVRETO N=220
Grades 1-4 (%) Grades 3-4 (%)
Musculoskeletal Disorders
Musculoskeletal Pain§ 32 0
Vascular
Hypertension|| 28 14**
Respiratory, thoracic, and mediastinal
Cough 23 0.5**
Infections
Pneumonia# 17 8

In 34 patients with RET fusion-positive solid tumors, no large mean increase in QTc (>20 ms) was detected in the study.

*Fatigue includes fatigue, asthenia; Edema includes edema peripheral, face edema, periorbital edema, eyelid edema, edema generalized, swelling; Diarrhea includes diarrhea, colitis, enteritis; §Musculoskeletal pain includes back pain, myalgia, arthralgia, pain in extremity, musculoskeletal pain, neck pain, musculoskeletal chest pain, bone pain, musculoskeletal stiffness, arthritis, spinal pain; ||Hypertension includes hypertension, blood pressure increased; Cough includes cough, productive cough, upper-airway cough syndrome; #Pneumonia includes pneumonia, atypical pneumonia, lung infection, pneumocystis jirovecii pneumonia, pneumonia bacterial, pneumonia cytomegaloviral, pneumonia haemophilus, pneumonia influenza, pneumonia streptococcal; **Only includes a Grade 3 adverse reaction.

The most common Grade 3-4 laboratory abnormalities (≥2%) were decreased lymphocytes, decreased neutrophils, decreased phosphate, decreased hemoglobin, decreased sodium, decreased calcium (corrected), and increased alanine aminotransferase (ALT).

Select laboratory abnormalities (≥20%) worsening from baseline in patients who received GAVRETO in ARROW

Laboratory Abnormality GAVRETO
N=220
Grades 1-4
(%)
Grades 3-4
(%)
Chemistry
Increased AST 69 1.1
Increased ALT 46 2.1
Increased creatinine 42 1.1
Increased alkaline phosphatase 40 1.1
Decreased calcium (corrected) 29 2.2
Laboratory Abnormality
(cont’d)
GAVRETO
N=220
Grades 1-4
(%)
Grades 3-4
(%)
Decreased sodium 27 3.2
Decreased phosphate 27 9
Hematology
Decreased hemoglobin 54 5
Decreased lymphocytes 52 20
Decreased neutrophils 52 10
Decreased platelets 26 0

Denominator for each laboratory parameter is based on the number of patients with a baseline and post-treatment laboratory value available, which ranged from 83 to 94 patients.

Clinically relevant laboratory abnormalities <20% of patients who received GAVRETO included hyperphosphatemia (10%).

To report suspected adverse reactions, contact Blueprint Medicines Corporation at 1-888-258-7768 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

ALT=increased alanine aminotransferase; AST=increased aspartate aminotransferase.