Telisotuzumab Vedotin-tllv (Monograph)

Brand name: Emrelis
Drug class: Antineoplastic Agents

Introduction

Telisotuzumab vedotin-tllv, a c-Met-directed antibody conjugated with the microtubule inhibitor monomethyl auristatin E (MMAE), is an antineoplastic agent.¹

Uses for Telisotuzumab Vedotin-tllv

Telisotuzumab vedotin-tllv has the following uses:

Telisotuzumab vedotin-tllv is indicated for the treatment of adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) with high c-Met protein overexpression [≥50% of tumor cells with strong (3+) staining], as determined by an FDA-approved test, who have received a prior systemic therapy.¹

This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR).¹ Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). ¹

Telisotuzumab Vedotin-tllv Dosage and Administration

General

Telisotuzumab vedotin-tllv is available in the following dosage form(s) and strength(s):

20 mg or 100 mg of telisotuzumab vedotin-tllv as a lyophilized powder in a single-dose vial for reconstitution and further dilution.¹

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

• For IV infusion only.¹

• The recommended dosage of telisotuzumab vedotin-tllv is 1.9 mg/kg (up to a maximum of 190 mg for patients greater than or equal to 100 kg) administered as an IV infusion over 30 minutes every 2 weeks until disease progression or unacceptable toxicity.¹

• Reconstitute and further dilute telisotuzumab vedotin-tllv prior to IV infusion.¹

• See Full Prescribing Information for additional instructions on preparation and administration, and dosage modification recommendations for adverse reactions.¹

Cautions for Telisotuzumab Vedotin-tllv

Contraindications

None.¹

Warnings/Precautions

Peripheral Neuropathy

Telisotuzumab vedotin-tllv can cause peripheral neuropathy, including peripheral sensory neuropathy and peripheral motor neuropathy.¹

In the safety population, peripheral neuropathy occurred in 51% of patients treated with telisotuzumab vedotin-tllv, including Grade 3 in 11%.¹ These adverse reactions included peripheral sensory neuropathy in 45% of patients and peripheral motor neuropathy in 9%.¹ The median time to onset of peripheral neuropathy was 105 days (range: 1 to 472 days).¹ Peripheral neuropathy led to permanent discontinuation of telisotuzumab vedotin-tllv in 13% of patients.¹ The median time to onset of peripheral neuropathy leading to treatment discontinuation was 249 days (range: 57 to 519 days).¹ Of the 7 patients with motor neuropathy ongoing as of their last dose of telisotuzumab vedotin-tllv, 6 had persistent Grade 1 or 2 symptoms 30 days after their last dose. ¹

Monitor patients for signs and symptoms of new or worsening peripheral neuropathy such as hypoesthesia, hyperesthesia, paresthesia, a burning sensation, neuropathic pain, or muscle weakness.¹ Withhold, reduce the dose or permanently discontinue telisotuzumab vedotin-tllv based on severity. ¹

Interstitial Lung Disease/Pneumonitis

Telisotuzumab vedotin-tllv can cause severe, life-threatening, or fatal interstitial lung disease (ILD)/pneumonitis.¹

In the safety population, ILD/pneumonitis occurred in 10% of patients treated with telisotuzumab vedotin-tllv, including Grade 3 in 3% and Grade 4 in 0.6%.¹ There were 3 fatal cases of ILD/pneumonitis in patients who received telisotuzumab vedotin-tllv.¹ The median time to onset of ILD/pneumonitis was 48 days (range: 23 to 85 days).¹ ILD/pneumonitis led to permanent discontinuation of telisotuzumab vedotin-tllv in 7% of patients.¹ The median time to onset of ILD/pneumonitis leading to treatment discontinuation was 46 days (range: 23 to 85 days).¹

Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms.¹ Monitor patients for signs and symptoms of ILD/pneumonitis.¹ Withhold or permanently discontinue telisotuzumab vedotin-tllv based on severity. ¹

Ocular Surface Disorders

Telisotuzumab vedotin-tllv can cause ocular surface disorders including blurred vision, visual impairment, keratitis, and dry eye.¹

In the safety population, ocular surface disorders occurred in 25% of patients treated with telisotuzumab vedotin-tllv.¹ The most common ocular surface disorders were blurred vision (15%), keratitis (11%), and dry eye (5%).¹ Grade 3 ocular surface disorders occurred in 1.2% of patients [blurred vision (1.2%), and keratitis (0.6%)].¹ The median time to onset of ocular surface disorders was 47 days (range: 1 to 319 days). ¹

Monitor patients for ocular surface disorders during treatment with telisotuzumab vedotin-tllv.¹ Withhold telisotuzumab vedotin-tllv and refer patients to an eye care professional for an ophthalmic examination and treatment for patients who develop Grade ≥2 ocular toxicity.¹ Withhold or permanently discontinue telisotuzumab vedotin-tllv based on severity. ¹

Infusion-Related Reactions

Telisotuzumab vedotin-tllv can cause infusion-related reactions (IRR); signs and symptoms of IRR include dyspnea, flushing, chills, nausea, chest discomfort, and hypotension.¹ The median time to onset of IRR was 28 days (range: 1 to 43 days). ¹

In the safety population, IRR occurred in 3% of patients treated with telisotuzumab vedotin-tllv including Grade 3 in 1.2% and Grade 4 in 0.6%.¹ IRR led to permanent discontinuation of telisotuzumab vedotin-tllv in 0.6% of patients.¹

Monitor patients for signs and symptoms of infusion reactions during telisotuzumab vedotin-tllv infusion.¹ Withhold, reduce the rate of infusion, or permanently discontinue telisotuzumab vedotin-tllv based on severity.¹ For patients who experience IRR, administer premedications prior to subsequent infusions.¹

Embryo-fetal Toxicity

Based on the mechanism of action and findings in animals, telisotuzumab vedotin-tllv can cause fetal harm when administered to a pregnant woman.¹ The small molecule component of telisotuzumab vedotin-tllv, MMAE, administered to rats caused adverse developmental outcomes, including embryo-fetal mortality and structural abnormalities, at exposures similar to those occurring clinically at the recommended dose.¹

Advise patients of the potential risk to a fetus.¹ Advise females of reproductive potential to use effective contraception during treatment with telisotuzumab vedotin-tllv and for 2 months after the last dose.¹ Advise male patients with female partners of reproductive potential to use effective contraception during treatment with telisotuzumab vedotin-tllv and for 4 months after the last dose. ¹

Specific Populations

Pregnancy

Based on the mechanism of action and findings in animals, telisotuzumab vedotin-tllv can cause fetal harm when administered to a pregnant woman.¹ There are no available human data on telisotuzumab vedotin-tllv use in pregnant women to inform a drug-associated risk.¹ In an animal reproduction study, administration of the small molecule component of telisotuzumab vedotin-tllv, MMAE, to pregnant rats during organogenesis resulted in embryo-fetal mortality and structural abnormalities at exposures similar to the clinical exposure at the recommended dose.¹ Advise patients of the potential risks to a fetus.¹

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.¹

Lactation

There are no data on the presence of telisotuzumab vedotin-tllv or MMAE in human milk, the effects on the breastfed child, or the effects on milk production.¹ Because of the potential for serious adverse reactions in a breastfed child, advise lactating women not to breastfeed during treatment with telisotuzumab vedotin-tllv and for 1 month after the last dose.¹

Females and Males of Reproductive Potential

Telisotuzumab vedotin-tllv can cause fetal harm when administered to a pregnant woman.¹

Verify pregnancy status in females of reproductive potential prior to initiating telisotuzumab vedotin-tllv treatment.¹

Advise females of reproductive potential to use effective contraception during treatment with telisotuzumab vedotin-tllv and for 2 months after the last dose. ¹

Based on genotoxicity findings, advise male patients with female partners of reproductive potential to use effective contraception during treatment with telisotuzumab vedotin-tllv and for 4 months after the last dose.¹

Based on findings in animal studies with MMAE-containing antibody-drug conjugates (ADCs), telisotuzumab vedotin-tllv may impair female fertility.¹ The effect on fertility is reversible.¹

Based on findings from animal studies, telisotuzumab vedotin-tllv may impair male fertility.¹ The reversibility of this effect is unknown.¹

Pediatric Use

Safety and effectiveness of telisotuzumab vedotin-tllv have not been established in pediatric patients.¹

Geriatric Use

Of the 168 patients with previously treated EGFR wild-type non-squamous NSCLC with c-Met protein overexpression treated with telisotuzumab vedotin-tllv in the LUMINOSITY study, 50% were ≥65 years of age and 12% were ≥75 years of age.¹ No overall differences in safety or effectiveness were observed between older and younger patients.¹

Hepatic Impairment

Avoid use of telisotuzumab vedotin-tllv in patients with moderate or severe hepatic impairment (total bilirubin >1.5 x ULN and any AST).¹

Patients with moderate or severe hepatic impairment are likely to have increased exposure to MMAE, which may increase the risk of adverse reactions.¹ Telisotuzumab vedotin-tllv has not been studied in patients with moderate or severe hepatic impairment.¹

No dosage adjustment is recommended for patients with mild hepatic impairment (total bilirubin ≤ULN and AST >ULN or total bilirubin >ULN and ≤1.5 x ULN and any AST).¹

Common Adverse Effects

The most common adverse reactions (≥20%) were peripheral neuropathy, fatigue, decreased appetite, and peripheral edema.¹

The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased lymphocytes, increased glucose, increased alanine aminotransferase, increased gamma glutamyl transferase, decreased phosphorus, decreased sodium, decreased hemoglobin, and decreased calcium.¹

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Strong CYP3A Inhibitors: concomitant use with telisotuzumab vedotin-tllv may increase the AUC of MMAE.¹ Monitor for increased risk of adverse reactions to telisotuzumab vedotin-tllv.¹

Actions

Mechanism of Action

Telisotuzumab vedotin-tllv is a c-Met-directed antibody drug conjugate (ADC).¹ The antibody is a humanized IgG1κ directed against c-Met, the cell surface receptor for hepatocyte growth factor.¹ The small molecule, MMAE, is a microtubule-disrupting agent, attached to the antibody via a protease cleavable linker.¹ Following binding to c-Met-expressing cells, telisotuzumab vedotin-tllv undergoes internalization and intracellular cleavage of MMAE.¹ MMAE disrupts the microtubule network of actively dividing cells, subsequently inducing cell cycle arrest and apoptotic cell death.¹ Telisotuzumab vedotin-tllv exhibited antitumor activity in xenograft models of NSCLC.¹

Advice to Patients

• Advise the patient to read the FDA-approved patient labeling.¹

• Advise patients that telisotuzumab vedotin-tllv can cause peripheral neuropathy.¹ Advise patients to report to their healthcare provider any new or worsening numbness or tingling of the hands or feet or any muscle weakness ¹

• Advise patients that telisotuzumab vedotin-tllv can cause ILD/pneumonitis.¹ Advise patients to immediately report to their healthcare provider any new or worsening respiratory symptoms ¹

• Advise patients that telisotuzumab vedotin-tllv can cause ocular surface disorders.¹ Advise patients to contact their healthcare provider any new or worsening ocular problems or vision changes. ¹

• Advise patients that telisotuzumab vedotin-tllv can cause infusion-related reactions.¹ Advise patients to immediately contact their healthcare provider if they experience signs and symptoms of infusion reactions, including fever, chills, rash, or breathing problems. ¹

• Advise pregnant women and females of reproductive potential of the potential risk to a fetus.¹ Advise female patients to contact their healthcare provider if they become pregnant, or if pregnancy is suspected, during treatment with telisotuzumab vedotin-tllv.¹

• Advise females of reproductive potential to use effective contraception during treatment and for 2 months after the last dose.¹

• Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 4 months after the last dose. ¹

• Advise women not to breastfeed during treatment with telisotuzumab vedotin-tllv and for 1 month after the last dose. ¹

• Advise males and females of reproductive potential that telisotuzumab vedotin-tllv may impair fertility.¹

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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