Tepmetko Adverse Reactions

The following adverse reactions are described in greater detail elsewhere in the labeling: Interstitial Lung Disease (see Precautions); Hepatotoxicity (see Precautions).
Clinical 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 practice.
The pooled safety population described in Precautions reflect exposure to TEPMETKO in 506 patients with solid tumors enrolled in five open-label, single-arm studies receiving TEPMETKO as single agent at a dose of 450 mg once daily. This included 313 patients with NSCLC positive for METex14 skipping alterations, who received TEPMETKO in VISION. Among 506 patients who received TEPMETKO, 44% were exposed for 6 months or longer, and 22% were exposed for greater than one year.
The data described as follows reflect exposure to TEPMETKO 450 mg once daily in 313 patients with metastatic non-small cell lung cancer (NSCLC) with METex14 skipping alterations in VISION (see Pharmacology: Pharmacodynamics under Actions).
Serious treatment-emergent adverse events occurred in 51% of patients who received TEPMETKO. Serious treatment-emergent adverse events in >2% of patients included pleural effusion (6.1%), pneumonia (5.4%), edema (5.1%), general health deterioration (3.8%), dyspnea (3.5%), musculoskeletal pain (2.9%), and pulmonary embolism (2.2%). Fatal adverse events occurred in one patient (0.3%) due to pneumonitis, and in one patient (0.3%) due to dyspnea from fluid overload.
Permanent discontinuation due to a treatment-emergent adverse event occurred in 24.9% of patients who received TEPMETKO. The most frequent treatment-emergent adverse events (>1%) leading to permanent discontinuations of TEPMETKO were edema (8%), pleural effusion (1.6%), and general health deterioration (1.6%).
Dosage interruptions due to a treatment-emergent adverse event occurred in 52.7% of patients who received TEPMETKO. Treatment-emergent adverse events which required dosage interruption in >2% of patients who received TEPMETKO included edema (28.4%), increased blood creatinine (5.8%), pleural effusion (3.5%), nausea (3.2%), increased ALT (2.9%), pneumonia (2.4%), decreased appetite (2.2%), and dyspnea (2.2%).
Dose reductions due to a treatment-emergent adverse event occurred in 36.1% of patients who received TEPMETKO. Treatment-emergent adverse events which required dose reductions in >2% of patients who received TEPMETKO included edema (21.7%), increased blood creatinine (2.6%), and pleural effusion (2.2%).
The most common adverse reactions (≥20%) in patients who received TEPMETKO were edema, nausea, fatigue, musculoskeletal pain, diarrhea, dyspnea, and decreased appetite. The most common Grade 3 to 4 laboratory abnormalities (≥2%) were decreased lymphocytes, decreased albumin, decreased sodium, increased gamma-glutamyltransferase, increased amylase, increased ALT, increased AST, and decreased hemoglobin.
Table 3 summarizes the adverse reactions in VISION. (See Table 3.)

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Clinically relevant adverse reactions in <10% of patients who received TEPMETKO included ILD/pneumonitis, rash, fever, dizziness, pruritus, and headache.
Table 4 summarizes the laboratory abnormalities observed in VISION. (See Table 4.)

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Increased creatinine: A median increase in serum creatinine of 30% was observed 21 days after initiation of treatment with TEPMETKO. The serum creatinine increases persisted throughout treatment and were reversible upon treatment completion.