HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use EXKIVITY safely and effectively. See full prescribing information for EXKIVITY. EXKIVITY® (mobocertinib) capsules, for oral use Initial U.S. Approval: 2021 WARNING: QTc PROLONGATION AND TORSADES DE POINTES See full prescribing information for complete boxed warning.  EXKIVITY can cause life-threatening heart rate-corrected QT (QTc) prolongation, including Torsades de Pointes, which can be fatal, and requires monitoring of QTc and electrolytes at baseline and periodically during treatment. Increase monitoring frequency in patients with risk factors for QTc prolongation (5.1).  Avoid use of concomitant drugs which are known to prolong the QTc interval and use of strong or moderate CYP3A inhibitors with EXKIVITY, which may further prolong the QTc (5.1, 7.1, 7.3).  Withhold, reduce the dose, or permanently discontinue EXKIVITY based on the severity of QTc prolongation (2.3). ----------------------------RECENT MAJOR CHANGES-------------------------- Dosage and Administration (2.3) 03/2023 -----------------------------INDICATIONS AND USAGE--------------------------- EXKIVITY is a kinase inhibitor indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). (1, 2.1) ------------------------DOSAGE AND ADMINISTRATION----------------------- Recommended Dosage: 160 mg orally once daily, with or without food. (2.2) ---------------------DOSAGE FORMS AND STRENGTHS---------------------- Capsules: 40 mg. (3) -------------------------------CONTRAINDICATIONS------------------------------- None. (4) ------------------------WARNINGS AND PRECAUTIONS-----------------------  Interstitial Lung Disease (ILD)/Pneumonitis: Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis. Immediately withhold EXKIVITY in patients with suspected ILD/pneumonitis and permanently discontinue EXKIVITY if ILD/pneumonitis is confirmed. (2.3, 5.2)  Cardiac Toxicity: Monitor cardiac function, including left ventricular ejection fraction, at baseline and during treatment. Withhold, resume at reduced dose or permanently discontinue based on severity. (2.3, 5.3)  Diarrhea: Diarrhea may lead to dehydration or electrolyte imbalance, with or without renal impairment. Monitor electrolytes and advise patients to start an antidiarrheal agent at first episode of diarrhea and to increase fluid and electrolyte intake. Withhold, reduce the dose, or permanently discontinue EXKIVITY based on the severity. (2.3, 5.4)  Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective non-hormonal contraception. (5.5, 8.1, 8.3) -------------------------------ADVERSE REACTIONS------------------------------ The most common (>20%) adverse reactions are 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. (6) To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals America, Inc. at 1-844-217-6468 or FDA at 1-800- FDA-1088 or www.fda.gov/medwatch. ------------------------------DRUG INTERACTIONS--------------------------------  CYP3A Inhibitors: Avoid concomitant use of EXKIVITY with strong or moderate CYP3A inhibitors. If concomitant use of a moderate CYP3A inhibitor is unavoidable, reduce the dose of EXKIVITY. (2.4, 7.1)  CYP3A Inducers: Avoid concomitant use of EXKIVITY with strong or moderate CYP3A inducers. (7.1) --------------------------USE IN SPECIFIC POPULATIONS--------------------- Lactation: Advise not to breastfeed. (8.2) See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling. Revised: 3/2023 FULL PRESCRIBING INFORMATION: CONTENTS* WARNING: QTc PROLONGATION AND TORSADES DE POINTES 1 INDICATIONS AND USAGE 2 DOSAGE AND ADMINISTRATION 2.1 Patient Selection 2.2 Recommended Dosage 2.3 Dosage Modifications for Adverse Reactions 2.4 Dosage Modifications for Moderate CYP3A Inhibitors 3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS 5 WARNINGS AND PRECAUTIONS 5.1 QTc Prolongation and Torsades de Pointes 5.2 Interstitial Lung Disease (ILD)/Pneumonitis 5.3 Cardiac Toxicity 5.4 Diarrhea 5.5 Embryo-Fetal Toxicity 6 ADVERSE REACTIONS 6.1 Clinical Trials Experience 7 DRUG INTERACTIONS 7.1 Effect of Other Drugs on EXKIVITY 7.2 Effect of EXKIVITY on Other Drugs 7.3 Drugs that Prolong the QTc Interval 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 8.2 Lactation 8.3 Females and Males of Reproductive Potential 8.4 Pediatric Use 8.5 Geriatric Use 8.6 Renal Impairment 8.7 Hepatic Impairment 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 12.2 Pharmacodynamics 12.3 Pharmacokinetics 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 13.2 Animal Toxicology and/or Pharmacology 14 CLINICAL STUDIES 16 HOW SUPPLIED/STORAGE AND HANDLING 17 PATIENT COUNSELING INFORMATION * Sections or subsections omitted from the full prescribing information are not listed. FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE EXKIVITY is indicated for the treatment of adult patients with locally advanced or metastatic nonsmall cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test [see Dosage and Administration (2.1)], whose disease has progressed on or after platinum-based chemotherapy. This indication is approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies (14)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). 2 DOSAGE AND ADMINISTRATION 2.1 Patient Selection Select patients with locally advanced or metastatic NSCLC for treatment with EXKIVITY based on the presence of EGFR exon 20 insertion mutations [see Clinical Studies (14)]. Information on FDAapproved tests is available at: http://www.fda.gov/CompanionDiagnostics. 2.2 Recommended Dosage The recommended dosage of EXKIVITY is 160 mg orally once daily until disease progression or unacceptable toxicity. Take EXKIVITY with or without food [see Clinical Pharmacology 12.3], at the same time each day. Swallow EXKIVITY capsules whole. Do not open, chew or dissolve the contents of the capsules. If a dose is missed by more than 6 hours, skip the dose and take the next dose the following day at its regularly scheduled time. If a dose is vomited, do not take an additional dose. Take the next dose as prescribed the following day. 2.3 Dosage Modifications for Adverse Reactions EXKIVITY dose reduction levels for adverse reactions are summarized in Table 1. WARNING: QTc PROLONGATION AND TORSADES DE POINTES  EXKIVITY can cause life threatening heart rate-corrected QT (QTc) prolongation, including Torsades de Pointes, which can be fatal, and requires monitoring of QTc and electrolytes at baseline and periodically during treatment. Increase monitoring frequency in patients with risk factors for QTc prolongation [see Warnings and Precautions (5.1)].  Avoid use of concomitant drugs which are known to prolong the QTc interval and use of strong or moderate CYP3A inhibitors with EXKIVITY, which may further prolong the QTc [see Warnings and Precautions (5.1), Drug Interactions (7.1, 7.3)].  Withhold, reduce the dose, or permanently discontinue EXKIVITY based on the severity of QTc prolongation [see Dosage and Administration (2.3)]. Table 1: Recommended EXKIVITY Dose Reductions Dose Reductions Dose Level First dose reduction 120 mg once daily Second dose reduction 80 mg once daily Recommended dosage modifications of EXKIVITY for adverse reactions are provided in Table 2. Table 2: Recommended Dosage Modifications for EXKIVITY Adverse Reactions Adverse Reaction Severity* EXKIVITY Dosage Modification QTc Interval Prolongation and Torsades de Pointes [see Warnings and Precautions (5.1)] Grade 2 (QTc interval 481-500 msec) First Occurrence  Withhold EXKIVITY until ≤ Grade 1 or baseline.  Upon recovery, resume EXKIVITY at the same dose. Recurrence  Withhold EXKIVITY until ≤ Grade 1 or baseline.  Upon recovery, resume EXKIVITY at the next lower dose or permanently discontinue EXKIVITY. Grade 3 (QTc interval ≥501 msec or QTc interval increase of >60 msec from baseline) First Occurrence  Withhold EXKIVITY until ≤ Grade 1 or baseline.  Upon recovery, resume EXKIVITY at the next lower dose or permanently discontinue EXKIVITY. Recurrence  Permanently discontinue EXKIVITY. Grade 4 (Torsades de Pointes; polymorphic ventricular tachycardia; signs/symptoms of serious arrhythmia)  Permanently discontinue EXKIVITY. Interstitial Lung Disease (ILD)/pneumonitis [see Warnings and Precautions (5.2)] Any grade  Withhold EXKVITY if ILD/pneumonitis is suspected.  Permanently discontinue EXKIVITY if ILD/pneumonitis is confirmed. Decreased Ejection Fraction or Heart Failure Grade 2 decreased ejection fraction  Withhold EXKIVITY until ≤ Grade 1 or baseline.  If recovered to baseline within 2 weeks, resume EXKIVITY at Adverse Reaction Severity* EXKIVITY Dosage Modification [see Warnings and Precautions (5.3)] the same dose or the next lower dose.  If not recovered to baseline within 2 weeks, permanently discontinue EXKIVITY. ≥ Grade 2 heart failure or Grade 3 or 4 decreased ejection fraction  Permanently discontinue EXKIVITY. Diarrhea [see Warnings and Precautions (5.4)] Intolerable or recurrent Grade 2 or Grade 3  Withhold EXKIVITY until ≤ Grade 1.  Resume EXKIVITY at the same dose or the next lower dose. Grade 4 First Occurrence  Withhold EXKIVITY until ≤ Grade 1.  Resume EXKIVITY at the next lower dose. Recurrence  Permanently discontinue EXKIVITY. Increased Amylase or Lipase [see Adverse Reactions (6.1)] Grade 3 without signs or symptoms  Withhold EXKIVITY until ≤ Grade 1.  Resume EXKIVITY at the same dose or next lower dose.  If not recovered to ≤ Grade 1 within 2 weeks, permanently discontinue EXKIVITY. Grade 3 with signs or symptoms  Withhold EXKIVITY until ≤ Grade 1.  Resume EXKIVITY at the next lower dose.  If not recovered to ≤ Grade 1 within 2 weeks, permanently discontinue EXKIVITY. Grade 4 First Occurrence  Withhold EXKIVITY until ≤ Grade 1.  Resume EXKIVITY at the next lower dose if recovery occurs within 2 weeks.  Permanently discontinue EXKIVITY if recovery does not occur within 2 weeks. Adverse Reaction Severity* EXKIVITY Dosage Modification Recurrence  Permanently discontinue EXKIVITY. Other Adverse Reactions [see Adverse Reactions (6.1)] Intolerable or recurrent Grade 2 or Grade 3  Withhold EXKIVITY until ≤ Grade 1.  Resume EXKIVITY at the same dose or the next lower dose. Grade 4 First Occurrence  Withhold EXKIVITY until ≤ Grade 1.  Resume EXKIVITY at the next lower dose if recovery occurs within 2 weeks.  Permanently discontinue EXKIVITY if recovery does not occur within 2 weeks. Recurrence  Permanently discontinue EXKIVITY. ULN = upper limit of normal * Graded per Common Terminology Criteria for Adverse Events Version 5.0 2.4 Dosage Modifications for Moderate CYP3A Inhibitors Avoid concomitant use of moderate CYP3A inhibitors with EXKIVITY. If concomitant use of a moderate CYP3A inhibitor cannot be avoided, reduce the EXKIVITY dose by approximately 50% (i.e., from 160 to 80 mg, 120 to 40 mg, or 80 to 40 mg) and monitor the QTc interval more frequently. After the moderate CYP3A inhibitor has been discontinued for 3 to 5 elimination half-lives, resume EXKIVITY at the dose taken prior to initiating the moderate CYP3A inhibitor [see Drug Interactions (7.1)]. 3 DOSAGE FORMS AND STRENGTHS Capsules: 40 mg, white, size 2, imprinted with “MB788” on the cap and “40mg” on the body in black ink. 4 CONTRAINDICATIONS None. 5 WARNINGS AND PRECAUTIONS 5.1 QTc Prolongation and Torsades de Pointes EXKIVITY can cause life-threatening heart rate-corrected QT (QTc) prolongation, including Torsades de Pointes, which can be fatal. In the 250 patient subset of the pooled EXKIVITY safety population who had scheduled and unscheduled electrocardiograms (ECGs) [see Adverse Reactions (6.1), Clinical Pharmacology (12.2)], 1.2% of patients had a QTc interval >500 msec and 11% of patients had a change-from-baseline QTc interval >60 msec. Grade 4 Torsades de Pointes occurred in 1 patient (0.4%). Clinical trials of EXKIVITY did not enroll patients with baseline QTc greater than 470 msec. Assess QTc and electrolytes at baseline and correct abnormalities in sodium, potassium, calcium, and magnesium prior to initiating EXKIVITY. Monitor QTc and electrolytes periodically during treatment. Increase monitoring frequency in patients with risk factors for QTc prolongation, such as patients with congenital long QT syndrome, heart disease, or electrolyte abnormalities. Avoid use of concomitant drugs which are known to prolong the QTc interval. Avoid concomitant use of strong or moderate CYP3A inhibitors with EXKIVITY [see Drug Interactions (7.1)], which may further prolong the QTc [see Drug Interactions (7.3)]. Withhold, reduce the dose, or permanently discontinue EXKIVITY based on the severity of the QTc prolongation [see Dosage and Administration (2.3)]. 5.2 Interstitial Lung Disease (ILD)/Pneumonitis EXKIVITY can cause ILD/pneumonitis, which can be fatal. In the pooled EXKIVITY safety population [see Adverse Reactions (6.1)], ILD/pneumonitis occurred in 4.3% of patients including 0.8% Grade 3 events and 1.2% fatal events. Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis. Immediately withhold EXKIVITY in patients with suspected ILD/pneumonitis and permanently discontinue EXKIVITY if ILD/pneumonitis is confirmed [see Dosage and Administration (2.3)]. 5.3 Cardiac Toxicity EXKIVITY can cause cardiac toxicity (including decreased ejection fraction, cardiomyopathy, and congestive heart failure) resulting in heart failure which can be fatal. In the pooled EXKIVITY safety population [see Adverse Reactions (6.1)], heart failure occurred in 2.7% of patients including 1.2% Grade 3 reactions, 0.4% Grade 4 reactions, and one (0.4%) fatal case of heart failure. EXKIVITY can cause QTc prolongation resulting in Torsades de Pointes [see Warnings and Precautions (5.1)]. Atrial fibrillation (1.6%), ventricular tachycardia (0.4%), first degree atrioventricular block (0.4%), second degree atrioventricular block (0.4%), left bundle branch block (0.4%), supraventricular extrasystoles (0.4%) and ventricular extrasystoles (0.4%) also occurred in patients receiving EXKIVITY. Monitor cardiac function, including assessment of left ventricular ejection fraction at baseline and during treatment. Withhold, reduce the dose, or permanently discontinue EXKIVITY based on the severity [see Dosage and Administration (2.3)]. 5.4 Diarrhea EXKIVITY can cause diarrhea, which can be severe. In the pooled EXKIVITY safety population [see Adverse Reactions (6.1)], diarrhea occurred in 93% of patients, including 20% Grade 3 and 0.4% Grade 4. The median time to first onset of diarrhea was 5 days but diarrhea has occurred within 24 hours after administration of EXKIVITY. In the 48% of patients whose diarrhea resolved, the median time to resolution was 3 days. Diarrhea may lead to dehydration or electrolyte imbalance, with or without renal impairment. Treat diarrhea promptly. Advise patients to start an antidiarrheal agent (e.g., loperamide) at first sign of diarrhea or increased bowel movement frequency and to increase fluid and electrolyte intake. Monitor electrolytes and withhold, reduce the dose or permanently discontinue EXKIVITY based on the severity [see Dosage and Administration (2.3)]. 5.5 Embryo-Fetal Toxicity Based on findings from animal studies and its mechanism of action, EXKIVITY can cause fetal harm when administered to a pregnant woman. Oral administration of mobocertinib to pregnant rats during the period of organogenesis resulted in embryolethality at maternal exposures approximately 1.7 times the human exposure based on area under the curve (AUC) at the 160 mg once daily clinical dose. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with EXKIVITY [see Drug Interactions (7.2)] and for 1 month after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with EXKIVITY and for 1 week after the last dose of EXKIVITY [see Use in Specific Populations (8.1, 8.3)]. 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling:  QTc Prolongation and Torsades de Pointes [see Warnings and Precautions (5.1)]  Interstitial Lung Disease (ILD)/Pneumonitis [see Warnings and Precautions (5.2)]  Cardiac Toxicity [see Warnings and Precautions (5.3)]  Diarrhea [see Warnings and Precautions (5.4)] 6.1 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 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.

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