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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)

15% of patients permanently discontinued GAVRETO due to any adverse reaction;
6.4% discontinued due to adverse reactions considered treatment-related by the trial investigator1,2

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 in 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 (%)
Fatigue 35 2.3**
Pyrexia 20 0
Edema 20 0
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
Hypertension|| 28 14**
Respiratory, thoracic, and mediastinal
Cough 23 0.5**
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
Grades 1-4 (%) Grades 3-4 (%)
Increased aspartate aminotransferase (AST) 69 1.1
Increased alanine aminotransferase (ALT) 46 2.1
Increased creatinine 42 1.1
Increased alkaline phosphatase 40 1.1
Decreased calcium (corrected) 29 2.2
Decreased sodium 27 3.2
Decreased phosphate 27 9
Laboratory Abnormality (cont'd) GAVRETO
Grades 1-4 (%) Grades 3-4 (%)
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.