GAVRETO was generally well tolerated in RET+ mNSCLC1

The safety of GAVRETO was evaluated as a single agent at 400 mg orally once daily in 438 patients, including RET fusion+ mNSCLC (n=220) and RET-altered thyroid cancer (n=138), in ARROW.

  • The most common adverse reactions (≥25%) were constipation, hypertension, fatigue, musculoskeletal pain and diarrhea.
  • The most common Grade 3-4 laboratory abnormalities (≥2%) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased phosphate, decreased calcium (corrected), decreased sodium, increased aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), decreased platelets, and increased alkaline phosphatase.
  • In 34 patients with RET-altered solid tumors, no large mean increase in QTc (>20 ms) was detected in the study.

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

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%).

Dose modifications and interruptions in RET fusion+ mNSCLC1

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 RET fusion-positive mNSCLC patients (n=220) 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
Musculoskeletal Disorders
Musculoskeletal Pain§ 32 0
Vascular
Hypertension|| 28 14**
Respiratory, thoracic, and mediastinal
Cough 23 0.5**
Infections
Pneumonia# 17 8
* 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.

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 aspartate aminotransferase (AST) 74 2.3
Increased alanine aminotransferase (ALT) 49 2.3
Increased alkaline phosphatase 42 1.8
Decreased calcium (corrected) 39 1.8
Decreased albumin 36 0
Decreased phosphate 35 11
Increased creatinine 33 0.5
Decreased sodium 29 7
Increased potassium 26 0.9
Hematology
Decreased neutrophils 61 16
Decreased hemoglobin 58 9
Decreased lymphocytes 56 19
Decreased platelets 27 3.2
* Denominator for each laboratory parameter is based on the number of patients with a baseline and post-treatment laboratory value available, which ranged from 216 to 218 patients.

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