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 WARNINGS AND PRECAUTIONS reflects exposure to EXKIVITY as a single agent at a dose of 160 mg orally once daily in 256 patients, including 114 patients with EGFR exon 20 insertion mutation-positive locally advanced or metastatic NSCLC from Study AP32788-15-101, and patients with other solid tumors. Forty-eight percent (48%) were exposed for 6 months or longer and 12% were exposed for greater than one year. The most common (>20%) adverse reactions were diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain. The most common (≥2%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes, increased amylase, increased lipase, decreased potassium, decreased hemoglobin, increased creatinine, and decreased magnesium. 

EGFR Exon 20 Insertion Mutation-Positive Locally Advanced or Metastatic NSCLC Previously Treated with Platinum-Based Chemotherapy

The safety of EXKIVITY was evaluated in a subset of patients in Study AP32788-15-101 with EGFR exon 20 insertion mutation-positive locally advanced or metastatic NSCLC who received prior platinum-based chemotherapy [see Clinical Studies (14)]. Patients with a history of interstitial lung disease, drug-related pneumonitis, radiation pneumonitis that required steroid treatment; significant, uncontrolled, active cardiovascular disease; or prolonged QTc interval were excluded from enrollment in this trial. A total of 114 patients received EXKIVITY 160 mg once daily until disease progression or unacceptable toxicity; 60% were exposed for 6 months or longer and 14% were exposed for greater than 1 year.

Serious adverse reactions occurred in 46% of patients who received EXKIVITY. Serious adverse reactions in ≥2% of patients included diarrhea, dyspnea, vomiting, pyrexia, acute kidney injury, nausea, pleural effusion, and cardiac failure. Fatal adverse reactions occurred in 1.8% of patients who received EXKIVITY, including cardiac failure (0.9%), and pneumonitis (0.9%).

Permanent discontinuation occurred in 17% of patients who received EXKIVITY. Adverse reactions requiring permanent discontinuation of EXKIVITY in at least ≥2% of patients were diarrhea and nausea.

Dosage interruptions of EXKIVITY due to an adverse reaction occurred in 51% of patients. Adverse reactions which required dosage interruption in >5% of patients included diarrhea, nausea and vomiting.

Dose reductions of EXKIVITY due to an adverse reaction occurred in 25% of patients. The adverse reaction requiring dose reduction in >5% of patients was diarrhea.

Table 3 summarizes the adverse reactions in Study AP32788-15-101.

Clinically relevant adverse reactions in <10% of patients receiving EXKIVITY included edema (9%), acute kidney injury (8%), peripheral neuropathy (7%), palmar-plantar erythrodysesthesia (4.4%), pneumonitis (2.6%) and cardiac failure (2.6%).

Table 4 summarizes the laboratory abnormalities in Study AP32788-15-101.