The following adverse reactions are discussed in greater detail in other sections of the labeling: Hepatotoxicity [see Warnings and Precautions (5.1) ] Left Ventricular Dysfunction [see Warnings and Precautions (5.2) ] Interstitial Lung Disease/Pneumonitis [see Warnings and Precautions (5.3) ] Most common adverse reactions (≥ 20%) are diarrhea, rash, hepatotoxicity, fatigue, nausea, musculoskeletal pain, and upper respiratory tract infection.
( 6.1 ) The most common (≥ 2%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes, increased alanine aminotransferase, increased aspartate aminotransferase, increased gamma glutamyl transferase, decreased potassium, and decreased neutrophils. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Boehringer Ingelheim Pharmaceuticals, Inc. at 1-800-542-6257 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The pooled safety population described in WARNINGS AND PRECAUTIONS reflects exposure to HERNEXEOS in 292 patients with unresectable or metastatic non-squamous NSCLC with HER2 (ERBB2) mutations who received HERNEXEOS as a single agent at 120 mg orally once daily until disease progression or unacceptable toxicity in Beamion LUNG-1 [see Clinical Studies (14) ] .
Among 292 patients who received HERNEXEOS, 59% of patients were exposed for 6 months or longer and 28% were exposed for greater than one year. In this pooled safety population, the most common (> 20%) adverse reactions were diarrhea (54%), rash (28%), hepatotoxicity (27%), fatigue (25%), nausea (23%), musculoskeletal pain (21%), and upper respiratory tract infection (20%). The most common (≥ 2%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes (10%), increased alanine aminotransferase (6%), increased aspartate aminotransferase (4.5%), increased gamma glutamyl transferase (2.8%), decreased potassium (2.4%), and decreased neutrophils (2.4%).
Beamion LUNG-1 The safety of HERNEXEOS was evaluated in Beamion LUNG-1 in 177 patients with unresectable or metastatic non-squamous NSCLC with HER2 tyrosine kinase domain (TKD) mutations; 72 patients had not received prior treatment; 105 patients had received prior platinum-based chemotherapy, and out of those patients, 34 patients had received prior treatment with a HER2-directed antibody drug conjugate (ADC) [see Clinical Studies (14) ] .
Patients received HERNEXEOS as a single agent at 120 mg once daily until disease progression or unacceptable toxicity. Among patients who received HERNEXEOS, 74% were exposed for 6 months or longer and 42% were exposed for greater than one year. The median age of patients who received HERNEXEOS was 63 years (range 30 to 88), 61% were female, 41% White, 48% Asian, and 0.6% Black or African American; 11% had unknown race data; 3.4% were of Hispanic or Latino ethnicity; and 38% had an Eastern Cooperative Oncology Group (ECOG) performance score of 0 and 62% had an ECOG performance score of 1.
Serious adverse reactions occurred in 36% of patients receiving HERNEXEOS. Serious adverse reactions in ≥ 2% of patients included pulmonary embolism (4%), dyspnea (3.4%), pneumonia (2.8%), hepatotoxicity, pleural effusion, and pericardial effusion (2.3%). Fatal adverse reactions occurred in one patient (0.6%) who received HERNEXEOS, due to pneumonia. Permanent discontinuation of HERNEXEOS due to an adverse reaction occurred in 6% of patients.
Adverse reactions which resulted in permanent discontinuation of HERNEXEOS were hepatotoxicity, decreased ejection fraction, anemia, increased blood alkaline phosphatase, diarrhea, dyspnea, increased gamma-glutamyl transferase, hemoptysis, pericardial effusion, pneumonitis, and pyrexia. Dosage interruption of HERNEXEOS due to an adverse reaction occurred in 34% of patients. Adverse reactions which required dosage interruption in ≥ 2% of patients were hepatotoxicity, decreased ejection fraction, diarrhea, COVID-19, rash, and vomiting.
Dose reductions of HERNEXEOS due to adverse reactions occurred in 9% of patients. Adverse reactions which required dose reductions in ≥ 1% of patients were hepatotoxicity, decreased ejection fraction, and diarrhea. Tables 3 and 4 summarize adverse reactions and laboratory abnormalities observed in Beamion LUNG-1. Table 3 Adverse Reactions (≥ 15%) in Patients with Non-Squamous NSCLC with HER2 TKD Mutations Who Received HERNEXEOS in Beamion LUNG-1 Adverse Reaction HERNEXEOS N = 177 All Grades 1 % Grade 3 or 4 % Events were graded using NCI CTCAE version 5.0. 1 No Grade 4 or Grade 5 adverse reactions occurred. *Grouped term.
Gastrointestinal Disorders Diarrhea* 56
