dosing and patient management guide

EXKIVITY™ (mobocertinib)THE FIRST ORAL THERAPY FOR EGFR EXON20 INSERTION+ mNSCLC PATIENTS POST PLATINUM-BASED CHEMOTHERAPY1

EGFR, epidermal growth factor receptor; mNSCLC, metastatic non-small cell lung cancer.

Please see Important Safety Information throughout and accompanying full Prescribing Information, including Boxed Warning.

DOSING AND PATIENT MANAGEMENT GUIDE

INDICATIONEXKIVITY is 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).

IMPORTANT SAFETY INFORMATION

APPROVEDNOW

WARNING: QTc PROLONGATION and TORSADES DE POINTESSee 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.

• 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.

• Withhold, reduce the dose, or permanently discontinue EXKIVITY based on the severity of QTc prolongation.

https://content.takeda.com/?contenttype=pi&product=exkivity&language=eng&country=usa&documentnumber=1

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OVERVIEW

Dear healthcare professional,

This Dosing and Patient Management Guide is provided to help you and your practice with strategies and information on how to start and support your patients throughout treatment with EXKIVITY™ (mobocertinib).

Your guide to treatment with EXKIVITY includes:

Additional resources• Takeda Oncology Here2Assist™ for patient access and

support (page 21)

• Questions? Visit EXKIVITYhcp.com to:– Find useful resources for you and your patients– Schedule an in-service with your representative

Recommended dosing regimen and considerations

Safety profile

Dose modifications for adverse reactions

Monitoring and management of QTc prolongation

Management of diarrhea and skin reactions

Patient counseling tips

*Median time to BICR-assessed confirmed response was 1.9 months.2 †Kaplan-Meier estimate in confirmed responders only.1

EXKIVITY™ (mobocertinib) overview• EXKIVITY is a kinase inhibitor of EGFR that inhibits and irreversibly binds to EGFR

Exon20 insertion mutations1

• EXKIVITY was evaluated in a pooled subset of 114 patients with EGFR Exon20 insertion+ metastatic or locally advanced NSCLC whose disease had progressed on or after platinum-based chemotherapy enrolled in an international, open-label, multicohort clinical trial. Patients received 160-mg dose of EXKIVITY once daily until disease progression or intolerable toxicity1

– Primary endpoint: Overall Response Rate by RECIST v1.11

– ORR by BICR: 28% (95% CI, 20-37; n=32/114)*1

– Median DOR by BICR: 17.5 months (95% CI, 7.4-20.3; n=32/114)†1

Investigator-assessed ORR was 35% (95% CI, 26-45) with a median DOR of 11.2 months.1

• The recommended dose is 160 mg orally (4 tablets), once daily, with or without food1

• The most common adverse reactions (>20%) were diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain1

IMPORTANT SAFETY INFORMATIONThe WARNINGS AND PRECAUTIONS for EXKIVITY include: QTc prolongation and Torsades de Pointes, interstitial lung disease (ILD)/pneumonitis, cardiac toxicity, diarrhea, and embryo-fetal toxicity.

BICR, blinded independent central review; CI, confidence interval; DOR, duration of response; EGFR, epidermal growth factor receptor; NSCLC, non-small cell lung cancer; ORR, overall response rate; QTc, corrected QT; RECIST v1.1, Response Evaluation Criteria In Solid Tumors, version 1.1.

See pages 22-23 for full details and complete Warnings and Precautions.

DOSINGSAFETY PROFILE

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IMPORTANT SAFETY INFORM

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https://www.exkivityhcp.com?utm_medium=qr&utm_source=USO-MOB-0086&utm_id=MC210908093401


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Inform patients to avoid grapefruit or grapefruit juice while taking EXKIVITY1


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ONCE-DAILY ORAL THERAPY APPROVED FOR EGFR EXON20 INSERTIONS

• Continue treatment with EXKIVITY™ (mobocertinib) until disease progression or unacceptable toxicity1

• EXKIVITY can be taken with or without food at approximately the same time each day1

• Patients should swallow EXKIVITY capsules whole and should not open, chew, or dissolve the contents of the capsules1

• If a patient misses a dose by more than 6 hours or if vomiting occurs, instruct the patient to resume treatment as prescribed the next day1

Recommended dosing regimen1

ONCE DAILY160 mg ORALLY WITH OR WITHOUT FOOD

DRUG INTERACTIONS1

CYP3A Inhibitors Coadministration of EXKIVITY with strong or moderate CYP3A inhibitors increased mobocertinib plasma concentrations, which may increase the risk of adverse reactions, including QTc interval prolongation. Avoid concomitant use of strong or moderate CYP3A inhibitors with EXKIVITY. If concomitant use of moderate CYP3A inhibitors cannot be avoided, reduce the EXKIVITY dose and monitor the QTc interval more frequently with ECGs.CYP3A Inducers Coadministration of EXKIVITY with strong or moderate CYP3A inducers decreased mobocertinib plasma concentrations, which may reduce EXKIVITY antitumor activity. Avoid concomitant use of strong or moderate CYP3A inducers with EXKIVITY.CYP3A SubstratesCoadministration of EXKIVITY with CYP3A substrates may decrease plasma concentrations of CYP3A substrates, which may reduce the efficacy of these substrates. Avoid concomitant use of hormonal contraceptives with EXKIVITY. Avoid concomitant use of EXKIVITY with other CYP3A substrates where minimal concentration changes may lead to serious therapeutic failures. If concomitant use is unavoidable, increase the CYP3A substrate dosage in accordance with the approved product Prescribing Information.Prolonged QTc IntervalEXKIVITY can cause QTc interval prolongation. Coadministration of EXKIVITY with drugs known to prolong the QTc interval may increase the risk of QTc interval prolongation. Avoid concomitant use of other medications known to prolong the QTc interval with EXKIVITY. If concomitant use is unavoidable, monitor the QTc interval more frequently with ECGs.

USE IN SPECIFIC POPULATIONS1 PregnancyBased on findings from animal studies and its mechanism of action, EXKIVITY can cause fetal harm when administered to a pregnant woman. There are no available data on EXKIVITY use in pregnant women. Advise pregnant women of the potential risk to a fetus.Females and Males of Reproductive PotentialVerify pregnancy status in females of reproductive potential prior to initiating EXKIVITY. Advise females of reproductive potential to use effective nonhormonal contraception during treatment with EXKIVITY 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.LactationThere are no data on the presence of mobocertinib or its metabolites in human milk or their effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with EXKIVITY and for 1 week after the last dose.

CYP3A, cytochrome p450, family 3, subfamily A; ECG, electrocardiogram; EGFR, epidermal growth factor receptor; QTc, corrected QT.


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• Serious adverse reactions occurred in 46% of patients. Serious adverse reactions in ≥2% of patients included diarrhea, dyspnea, vomiting, pyrexia, acute kidney injury, nausea, pleural effusion, and cardiac failure1

• Fatal adverse reactions occurred in 1.8% of patients, including cardiac failure (0.9%) and pneumonitis (0.9%)1

• Clinically relevant adverse reactions in <10% of patients receiving EXKIVITY included edema (9%), acute kidney injury (8%), peripheral neuropathy (7%), palmar-plantar erythrodysaesthesia (4.4%), pneumonitis (2.6%), and cardiac failure (2.6%)1

qd, once daily; QTc, corrected QT.

SAFETY PROFILE

Diarrhea

Stomatitis†

Vomiting

Decreased appetite

Nausea

Decreased weight

Abdominal pain§

Gastroesophageal reflux disease

Dyspepsia

Gastrointestinal Disorders

Skin and Subcutaneous Tissue Disorders

Oral EXKIVITY™ (mobocertinib) 160 mg qd (N=114)Adverse Reaction1

All Grades*

92%

46%

40%

39%

37%

21%

18%

15%

11%

78%

39%

32%

24%

19%

34% 2.6%‡

29% 3.5%‡

10% 0

24%

16%

15%

13%

0

0

4.4%

0

10%

10%

3.5%

4.4%‡

Grade 3 or 4

22%

4.4%‡

2.6%‡

0.9%‡

4.4%‡

0

1.8%‡

0

0

1.8%‡

0.9%‡

0

0.9%‡

0

Rash||

Paronychia¶

Dry skin

Pruritus

Alopecia

QTc interval prolongation¶¶

Hypertension##

Cardiac Disorders

Headache

Nervous System Disorders

Cough††

Upper respiratory tract infection‡‡

Dyspnea§§

Rhinorrhea

Respiratory, Thoracic, and Mediastinal Disorders

Musculoskeletal pain#

Musculoskeletal and Connective Tissue Disorders

Fatigue**

General Disorders and Administration Site Conditions

11% 0Ocular toxicity||||

Eye Disorders

Adverse reactions (≥10%) in patients1

who were previously treated with platinum-based chemotherapy (N=114)

*Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0). †Stomatitis includes angular cheilitis, aphthous ulcer, cheilitis, mouth ulceration, mucosal inflammation, odynophagia, and stomatitis. ‡Events of Grade 3 only (no Grade 4 occurred). §Abdominal pain includes abdominal discomfort, abdominal pain, abdominal pain upper, abdominal tenderness, and gastrointestinal pain. ||Rash includes acne, dermatitis, dermatitis acneiform, rash, rash macular, rash maculopapular, rash papular, rash pruritic, rash pustular, and urticaria. ¶Paronychia includes nail bed tenderness, nail disorder, nail infection, onycholysis, and paronychia. #Musculoskeletal pain includes arthralgia, back pain, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal pain, myalgia, neck pain, non-cardiac chest pain, pain in extremity, and spinal pain. **Fatigue includes asthenia and fatigue. ††Cough includes cough, productive cough, and upper-airway cough syndrome. ‡‡Upper respiratory tract infection includes nasopharyngitis, pharyngitis, respiratory tract infection, rhinitis, sinusitis, and upper respiratory tract infection. §§Dyspnea includes dyspnea, and dyspnea exertional. ||||Ocular toxicity includes dry eye, eye pruritus, abnormal sensation in eye, eye discharge, blepharitis, trichiasis, conjunctival hemorrhage, vitreous floaters, blurred vision and corneal edema. ¶¶QTc interval prolongation includes electrocardiogram QT prolonged, and ventricular arrhythmia. ##Hypertension includes blood pressure increased, and hypertension.1


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SAFETY PROFILE (CONT’D)

The denominator used to calculate the rate varied from 93 to 113 based on the number of patients with a baseline and at least one post-treatment value. The laboratory abnormalities are values that reflect worsening from baseline. †Grades per NCI CTCAE v5.0.1

CTCAE, Common Terminology Criteria for Adverse Events; NCI, National Cancer Institute; qd, once daily.

Decreased red blood cells

Decreased lymphocytes

Decreased platelets

Decreased leukocytes

Increased creatinine

Increased amylase

Increased lipase

Decreased potassium

Increased alkaline phosphatase

Decreased albumin

Decreased magnesium

Increased alanine aminotransferase

Increased aspartate aminotransferase

Decreased sodium

Hematology

Chemistry

Oral EXKIVITY™ (mobocertinib)* 160 mg qd (N=114)Laboratory Abnormality1

All Grades†

59%

52%

26%

25%

52%

40%

35%

29%

25%

23%

23%

22%

21%

20%

Grade 3 or 4

3.5%

15%

0.9%

0

2.7%

13%

10%

5.3%

1.8%

1.8%

2.7%

2.7%

1.8%

0.9%

Select laboratory abnormalities (≥20%) worsening from baseline1 in patients who were previously treated with platinum-based chemotherapy (N=114)

*


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RECOMMENDED DOSE MODIFICATIONS FOR MANAGEMENT OF ADVERSE REACTIONS

Severity* Dose ModificationAdverse Reaction1

QTc Interval Prolongation and Torsades de Pointes

Grade 2 (QTc interval 481-500 msec)

Grade 3 (QTc interval ≥501 msec or QTc interval increase of >60 msec from baseline)

First OccurrenceWithhold EXKIVITY until ≤ Grade 1 or baseline. Upon recovery, resume EXKIVITY at the same dose RecurrenceWithhold EXKIVITY until ≤ Grade 1 or baseline. Upon recovery, resume EXKIVITY at the next lower dose or permanently discontinue EXKIVITY

First OccurrenceWithhold EXKIVITY until ≤ Grade 1 or baseline. Upon recovery, resume EXKIVITY at the next lower dose or permanently discontinue EXKIVITYRecurrencePermanently discontinue EXKIVITY

Grade 4 (Torsades de Pointes; polymorphic ventricular tachycardia; signs/symptoms of serious arrhythmia)

Permanently discontinue EXKIVITY

Interstitial Lung Disease/Pneumonitis

Any grade Withhold EXKIVITY if ILD/pneumonitis is suspectedPermanently 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 the same dose or the next lower doseIf 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

80 mg ONCE DAILY

SECOND REDUCTION

120 mg ONCE DAILY

FIRST REDUCTION

160 mg ONCE DAILY

Dose modifications1

STARTING DOSE

Diarrhea

Severity* Dose ModificationAdverse Reaction1

Intolerable or recurrent Grade 2 or Grade 3

Grade 4 First OccurrenceWithhold EXKIVITY until ≤ Grade 1Resume EXKIVITY at the next lower doseRecurrencePermanently discontinue EXKIVITY

Grade 4 First OccurrenceWithhold EXKIVITY until ≤ Grade 1Resume EXKIVITY at the next lower dose if recovery occurs within 2 weeksPermanently discontinue EXKIVITY if recovery does not occur within 2 weeksRecurrencePermanently discontinue EXKIVITY

Other Adverse Reactions


Withhold EXKIVITY until ≤ Grade 1Resume EXKIVITY at the same dose or the next lower dose

Withhold EXKIVITY until ≤ Grade 1Resume EXKIVITY at the same dose or the next lower dose

*Graded per NCI CTCAE v5.0.1

• Dose reductions due to adverse reactions occurred in 25% of patients.1 The adverse reaction requiring dose reduction in >5% of patients was diarrhea1

• Dose interruptions due to adverse reactions occurred in 51% of patients.1 The adverse reactions requiring dose interruption in >5% of patients included diarrhea, nausea, and vomiting1

• Permanent discontinuation due to adverse reactions occurred in 17% of patients.1 The adverse reactions requiring permanent discontinuation of EXKIVITY in ≥2% of patients were diarrhea and nausea1

CTCAE, Common Terminology Criteria for Adverse Events; ILD, interstitial lung disease; NCI, National Cancer Institute; QTc, corrected QT.


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MONITORING AND MANAGING QTc INTERVAL PROLONGATION

Incidence1

In the 250-patient subset of the pooled EXKIVITY™ (mobocertinib) safety population (N=256) who had scheduled and unscheduled ECGs, 11% had a >60-msec change from baseline in QTc interval, and 1.2% had a QTc interval >500 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

Dose modifications and Common Terminology Criteria for Adverse Events (CTCAE) definition of QTc interval prolongation by grade

Dose Modification1

First OccurrenceWithhold EXKIVITY until ≤ Grade 1 or baseline. Upon recovery, resume EXKIVITY at the same doseRecurrenceWithhold EXKIVITY until ≤ Grade 1 or baseline. Upon recovery, resume EXKIVITY at the next lower dose or permanently discontinue EXKIVITY

First OccurrenceWithhold EXKIVITY until ≤ Grade 1 or baseline. Upon recovery, resume EXKIVITY at the next lower dose or permanently discontinue EXKIVITY RecurrencePermanently discontinueEXKIVITY

Permanently discontinueEXKIVITY

CTCAEDefinition2

Grade 2

Average QTc interval 481-500 msec

Grade 3

Average QTc interval≥501 msec; >60-msec change from baseline

Grade 4

Torsades de Pointes; polymorphic ventricular tachycardia; signs/symptoms of serious arrhythmia

Grade 1

Average QTc interval 450-480 msec

N/A

WARNING: QTc PROLONGATION and TORSADES DE POINTESSee 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.



Monitoring1 • Assess QTc interval and electrolytes at baseline and correct abnormalities in sodium,

potassium, calcium, and magnesium prior to initiating EXKIVITY

• Monitor QTc interval and electrolytes periodically during treatment. Increase monitoring frequency in patients with risk factors for QTc interval prolongation, such as patients with congenital long QT syndrome, heart disease, or electrolyte abnormalities

Concomitant use with other medications1 • Avoid concomitant use of other medications known to prolong the QTc interval with

EXKIVITY, including strong or moderate CYP3A inhibitors

• If concomitant use of moderate CYP3A inhibitors cannot be avoided, reduce the EXKIVITY dose by approximately 50% (ie, 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

Patient counseling information1 • Inform patients of the risk of QTc interval prolongation • Symptoms that may be indicative of significant QTc interval prolongation include: – Dizziness – Lightheadedness – Syncope • Advise patients to report these symptoms and to inform you about the use of any

heart medications

CTCAE, Common Terminology Criteria for Adverse Events; CYP3A, cytochrome p450, family 3, subfamily A; ECG, electrocardiogram; N/A, not applicable; QTc, corrected QT.


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MANAGING DIARRHEA EVENTS

Diarrhea

All GradesAdverse Reaction1Oral EXKIVITY™ (mobocertinib) 160 mg qd (N=114)

92%

Grade 3 or 4

22%

In the clinical trial, diarrhea was common, usually transient and should be treated promptly with supportive strategies1

Dose modifications and CTCAE definition of diarrhea by grade

Dose Modification1

For intolerable or recurrent Grade 2 diarrhea, withhold EXKIVITY until recovery to ≤ Grade 1; then resume EXKIVITY at the same or next lower dose

Withhold EXKIVITY until recovery to ≤ Grade 1; then resume EXKIVITY at the same or next lower dose

Withhold EXKIVITY until recovery to ≤ Grade 1;then resume EXKIVITY at the next lower dose. Permanently discontinueEXKIVITY for recurrent Grade 4toxicity

CTCAEDefinition2

Grade 2

Increase of 4-6 stools per day over baseline; moderate increase in ostomy output compared to baseline; limiting instrumental ADL

Grade 3

Increase of greater than or equal to 7 stools per day over baseline; hospitalization indicated; severe increase in ostomy output compared to baseline; limiting self-care ADL

Grade 4

Life-threateningconsequences;urgent interventionindicated

No dose modificationis required. Initiate treatment with antidiarrhealmedicinal products(eg, loperamide) at first onset of diarrhea

Grade 1

Increase of less than 4 stools per day over baseline; mild increase in ostomy output compared to baseline

In the pooled safety population, diarrhea occurred in 93% of patients, including Grade 1 or 2 diarrhea in 72.6% of patients, Grade 3 in 20%, and Grade 4 in 0.4%.1

The manufacturer does not endorse these organizations. Takeda is not responsible for the content provided by any third-party organization. The online resources are provided for informational purposes only and are not meant to replace your clinical judgment.

Read this paper on assessment and management of EGFR TKI–induced diarrhea.

Management of Diarrhea Induced by Epidermal Growth Factor Receptor Tyrosine Kinase by Hirsh et al (free access)

ANTICIPATE: Proactively counsel your patients as diarrhea could occur as soon as 24 hours after administration of EXKIVITY1

Instruct patients to have an antidiarrheal (eg, loperamide) readily available to help address first sign of diarrhea or increased bowel movement frequency. Instruct them to also increase oral fluids and electrolyte intake.1

Treat with an antidiarrheal and adequate fluid intake per your clinical practice.1

• If using loperamide as the antidiarrheal treatment, refer to loperamide product labeling for additional information1

ADDRESS: Treat diarrhea promptly at first episode of loose stool1

• Monitor electrolytes and instruct patients to increase fluid and electrolyte intake1

• In the clinical trial, IV hydration was considered for Grade 4 diarrhea3

Median time to first ONSET

5 days5 daysMedian time to RESOLUTION

in the 48% of patients whose diarrhea resolved1

but may occur throughout therapy1

3 days3 days

See patient counseling tips for diarrhea on page 16

ADL, activities of daily living; CTCAE, Common Terminology Criteria for Adverse Events; EGFR, epidermal growth factor receptor; IV, intravenous; qd, once daily; TKI, tyrosine kinase inhibitor.


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4257116/

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MANAGING DIARRHEA EVENTS (CONT’D)

Patient counseling information1

Before starting treatment, ensure patients understand the importance of openly and rapidly communicating about adverse events, especially diarrhea. Establish baseline bowel movements and make sure patients have an antidiarrheal (eg, loperamide) readily available to help address first evidence of increased frequency or first episode of unformed, loose stool.

• Advise patients that diarrhea which may be severe occurs commonly during treatment with EXKIVITY™ (mobocertinib) and should be treated promptly

• Advise patients to have antidiarrheal medicine readily available and promptly start antidiarrheal treatment (eg, loperamide), increase oral fluids and electrolyte intake, and contact their healthcare provider if diarrhea occurs

Let patients know who they should contact from their healthcare team if any of the following occur1:• Symptoms of dehydration, such as lightheadedness, dizziness, or fainting• Inability to take fluids by mouth due to nausea or vomiting• Inability to get diarrhea under control within 24 hours

Discuss dietary changes with your patientsEating simply and staying hydrated can help your patients manage their diarrhea. Consider referring patients to a nutritionist or dietitian for a personalized approach.

Consume foods that are high in potassium and sodium (eg, bananas, apricots, broths, and sports drinks)4

Consume more small meals each day instead of 3 large meals5 Maintain adequate fluid intake (~8 cups of clear liquid per day), preferably using fluids that help replace lost electrolytes1,6

Eliminate dairy and foods that are greasy, spicy, or fried, as well as cruciferous vegetables (eg, broccoli, cabbage, cauliflower)7


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All Grades*Adverse Reaction1Oral EXKIVITY™ (mobocertinib) 160 mg qd (N=114)

Grade 3 or 4

1.8%‡

0.9%‡

00.9%‡

78%39%32%24%

Skin and Subcutaneous Tissue Disorders Rash†

Paronychia§

Dry skin Pruritus

Dose Modification

EXKIVITY dose modification guidelines for other adverse reactions1

Grade 4

Withhold EXKIVITY until ≤ Grade 1 and then resume EXKIVITY at the same or next lower dose

First OccurrenceWithhold EXKIVITY until ≤ Grade 1Resume EXKIVITY at the next lower dose if recovery occurs within 2 weeksPermanently discontinue EXKIVITY if recovery does not occur within 2 weeksRecurrencePermanently discontinue EXKIVITY


MANAGING SKIN REACTIONS

Management of skin reactions may include dose modification1

In the clinical trial, skin reactions were common and were managed with supportive strategies1

The manufacturer does not endorse these organizations. Takeda is not responsible for the content provided by any third-party organization. The online resources are provided for informational purposes only and are not meant to replace your clinical judgment.

A Comprehensive Review of Contemporary Literature for Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer and Their Toxicity by Lee et al (free access)Additional resources for managing EGFR inhibitor–induced cutaneous skin toxicities are available. *Graded according to NCI CTCAE v5.0. †Rash includes acne, dermatitis, dermatitis acneiform, rash, rash macular, rash

maculopapular, rash papular, rash pruritic, rash pustular, and urticaria. ‡Events of Grade 3 only (no Grade 4 events occurred).

§Paronychia includes nail bed tenderness, nail disorder, nail infection, onycholysis, and paronychia.1

Skin reaction management Consult with your patient throughout treatment. If rash, dry skin, pruritus, or paronychia is resistant to management, consider referring your patient to a specialist. The below includes some general management information based on clinical practice.• Refer patients to a dermatologist when they have a preexisting skin condition (eg,

active rosacea, acne, or eczema)8

• Prescribe prophylactic oral antibiotics if patients are concerned about developing a rash9

• Prescribe topical corticosteroids and oral antibiotics to supplement patients’ usual skincare for Grade 1-3 rash9

• For moderate paronychia, prescribe potent topical steroid cream (betamethasone 0.1%) applied under occlusion until clinical improvement or review. If purulent, culture and consider prescribing an oral antibiotic8

• At every treatment cycle, record a skin toxicity assessment and continue preventive treatment plus advice8

CTCAE, Common Terminology Criteria for Adverse Events; EGFR, epidermal growth factor receptor; NCI, National Cancer Institute; qd, once daily.

See patient counseling tips for skin reactions on page 20


https://pubmed.ncbi.nlm.nih.gov/33117017/

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Patient counseling information Rash and dry skin If patients experience common skin reactions such as rash and dry skin while using EXKIVITY™ (mobocertinib), counsel them to take preventive and proactive steps, such as:

• Minimize sun exposure, apply sunscreen regularly, and wear sun-protective clothing such as wide-brim hats and loose-fitting, long-sleeve shirts10,11

• Keep skin soft by using an alcohol- and perfume-free skin cream often8,11

• Avoid hot showers or baths—use lukewarm water instead8,11

• Avoid scratching the skin

• Use a gentle cleanser10,11

Remind patients to speak up if skin-related side effects affect their ability to carry out normal daily activities. Let them know you are here to help support them along their treatment journey and can tailor the

treatment so it works for them

MANAGING SKIN REACTIONS (CONT’D)


Paronychia While taking EXKIVITY, patients may experience paronychia, a disorder characterized by inflammation of the soft tissue around the nails. Help your patients by recommending the following preventive measures1,8:

• Avoid nail trauma such as manicures/pedicures and putting pressure on the nail bed11,12

• Keep affected areas dry and avoid exposure to moisture11

• Wear gloves when washing dishes and using household cleaning products11

• Avoid tight-fitting shoes11

ACCESS SUPPORT: Takeda Oncology Here2Assist case managers can work with your patients to determine their coverage options and provide additional support to patients throughout their treatment

HELPFUL RESOURCES: Takeda Oncology Here2Assist case managers can provide your patients with information about additional resources that may assist with the day-to-day support they need

FINANCIAL ASSISTANCE: Takeda Oncology Here2Assist case managers can help identify financial assistance programs that may be able to help your patients with the cost of their treatment

Takeda Oncology Here2Assist is a comprehensive patient support program that: • Works with your patients’ insurance company to help get your patients started on their

medication • Identifies available financial assistance that may be right for your patients • May help eligible patients get started on treatment in the event of an insurance delay • Identifies specialty pharmacies to help fill and ship your patients’ prescriptions

appropriately • Conducts regular follow-up calls to patients • Sends text message status updates and reminders to patients* • Connects your patients with nurse navigators to support their product

education journey

For more information about access support and financial assistance that your patients may qualify for,

visit www.Here2Assist.com/hcp or call us at 1-844-817-6468, Option 2.

We’re available Monday-Friday, 8 am-8 pm ET.

*Patients will need to enroll in the texting program to receive text messages.

Takeda Oncology Here2Assist™


https://www.here2assist.com/hcp/home

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ATIONOVERVIEW

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS QTc Prolongation and Torsades de PointesEXKIVITY 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), 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, which may further prolong the QTc. Withhold, reduce the dose, or permanently discontinue EXKIVITY based on the severity of the QTc prolongation.Interstitial Lung Disease (ILD)/PneumonitisEXKIVITY can cause ILD/pneumonitis, which can be fatal. In the pooled EXKIVITY safety population, 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.Cardiac ToxicityEXKIVITY 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, 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. 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.Diarrhea EXKIVITY can cause diarrhea, which can be severe. In the pooled EXKIVITY safety population, 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 (eg, 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.Embryo-Fetal ToxicityBased on findings from animal studies and its mechanism of action, EXKIVITY can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective nonhormonal contraception during treatment with EXKIVITY 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.

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.



References: 1. Exkivity. Prescribing information. Takeda Pharmaceuticals America, Inc; 2021. 2. U.S. Department of Health and Human Services. Common terminology criteria for adverse events (CTCAE) version 5.0. Published November 27, 2017. Accessed June 11, 2021. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x7.pdf. 3. Data on file. Exkivity DOF 005 Diarrhea Protocol, June 2021. Takeda Pharmaceuticals, Inc. 4. American Cancer Society. Diarrhea. Accessed June 11, 2021. https://www.cancer.org/treatment/treatments-and-side-effects/physical-side-effects/stool-or-urine-changes/diarrhea.html. 5. National Cancer Institute. Gastrointestinal complications (PDQ®)–patient version. Accessed June 11, 2021. https://www.cancer.gov/about-cancer/treatment/side-effects/constipation/gi-complications-pdq. 6. American Cancer Society. Nutrition for the person with cancer during treatment: a guide for patients and families. Accessed June 11, 2021. https://www.cancer.org/content/dam/cancer-org/cancer-control/en/booklets-flyers/nutrition-for-the-patient-with-cancer-during-treatment.pdf. 7. National Cancer Institute. Nutrition in cancer care (PDQ®)–health professional version. Accessed June 11, 2021. https://www.cancer.gov/about-cancer/treatment/side-effects/appetite-loss/nutrition-hp-pdq. 8. Beech J et al. Future Oncol. 2018;14(24):2531-2541. 9. Williams LA et al. Oncol Nurs Forum. 2020;47(5):539-556. 10. American Cancer Society. Skin rash. Accessed May 1, 2021. https://www.cancer.org/treatment/treatments-and-side-effects/physical-side-effects/skin-problems/skin-rash.html. 11. National Cancer Institute. Skin and nail changes during cancer treatment. Accessed May 1, 2021. https://www.cancer.gov/about-cancer/treatment/side-effects/skin-nail-changes. 12. American Cancer Society. Nail changes. Accessed June 16, 2021 https://www.cancer.org/treatment/treatments-and-side-effects/physical-side-effects/nail-changes.html.

To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals U.S.A., Inc. at 1-844-217-6468 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see accompanying full Prescribing Information, including Boxed Warning.

ADVERSE REACTIONSThe 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.DRUG INTERACTIONSCYP3A Inhibitors Coadministration of EXKIVITY with strong or moderate CYP3A inhibitors increased mobocertinib plasma concentrations, which may increase the risk of adverse reactions, including QTc interval prolongation. Avoid concomitant use of strong or moderate CYP3A inhibitors with EXKIVITY. If concomitant use of moderate CYP3A inhibitors cannot be avoided, reduce the EXKIVITY dose and monitor the QTc interval more frequently with ECGs.CYP3A InducersCoadministration of EXKIVITY with strong or moderate CYP3A inducers decreased mobocertinib plasma concentrations, which may reduce EXKIVITY antitumor activity. Avoid concomitant use of strong or moderate CYP3A inducers with EXKIVITY.CYP3A SubstratesCoadministration of EXKIVITY with CYP3A substrates may decrease plasma concentrations of CYP3A substrates, which may reduce the efficacy of these substrates. Avoid concomitant use of hormonal contraceptives with EXKIVITY. Avoid concomitant use of EXKIVITY with other CYP3A substrates where minimal concentration changes may lead to serious therapeutic failures. If concomitant use is unavoidable, increase the CYP3A substrate dosage in accordance with the approved product Prescribing Information.Prolonged QTc IntervalEXKIVITY can cause QTc interval prolongation. Coadministration of EXKIVITY with drugs known to prolong the QTc interval may increase the risk of QTc interval prolongation. Avoid concomitant use of other medications known to prolong the QTc interval with EXKIVITY. If concomitant use is unavoidable, monitor the QTc interval more frequently with ECGs.USE IN SPECIFIC POPULATIONS PregnancyBased on findings from animal studies and its mechanism of action, EXKIVITY can cause fetal harm when administered to a pregnant woman. There are no available data on EXKIVITY use in pregnant women. Advise pregnant women of the potential risk to a fetus.Females and Males of Reproductive Potential Verify pregnancy status in females of reproductive potential prior to initiating EXKIVITY. Advise females of reproductive potential to use effective nonhormonal contraception during treatment with EXKIVITY 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.Lactation There are no data on the presence of mobocertinib or its metabolites in human milk or their effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with EXKIVITY and for 1 week after the last dose.


https://www.fda.gov/safety/medwatch-fda-safety-information-and-adverse-event-reporting-program

ONCE DAILY160 mg ORALLY WITH OR WITHOUT FOOD

APPROVEDNOW EXKIVITY™ (mobocertinib)

THE FIRST ORAL THERAPY FOR EGFR EXON20 INSERTION+ mNSCLC PATIENTS POST PLATINUM-BASED CHEMOTHERAPY1

The recommended starting dose of EXKIVITY is 160 mg orally, once daily, with or without food1

Help your patients start and stay on track with proactive patient counseling and early management of adverse reactions

• Continue treatment with EXKIVITY until disease progression or unacceptable toxicity1

INDICATIONEXKIVITY is 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). IMPORTANT SAFETY INFORMATION The WARNINGS AND PRECAUTIONS for EXKIVITY include: QTc prolongation and Torsades de Pointes, interstitial lung disease (ILD)/pneumonitis, cardiac toxicity, diarrhea, and embryo-fetal toxicity.To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals U.S.A., Inc. at 1-844-217-6468 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.


Visit EXKIVITYhcp.com to:• Find useful resources for you and your patients• Schedule an in-service with your representative

EGFR, epidermal growth factor receptor; mNSCLC, metastatic non-small cell lung cancer.

All trademarks are property of their respective owners. ©2021 Takeda Pharmaceuticals U.S.A., Inc. All rights reserved. 10/21 USO-MOB-0086


https://www.fda.gov/safety/medwatch-fda-safety-information-and-adverse-event-reporting-program



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