Loncastuximab tesirine-lpyl

Loncastuximab tesirine-lpyl
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Parth Vikram Singh, MBBS[2]

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Overview

Loncastuximab tesirine-lpyl is a CD19-directed antibody and alkylating agent that is FDA approved for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low-grade lymphoma, and high-grade B-cell lymphoma.. Common adverse reactions include thrombocytopenia, increased gamma-glutamyltransferase, neutropenia, anemia, hyperglycemia, transaminase elevation, fatigue, hypoalbuminemia, rash, edema, nausea, and musculoskeletal pain..

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

There is limited information regarding Loncastuximab tesirine-lpyl FDA-Labeled Indications and Dosage (Adult) in the drug label.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Loncastuximab tesirine-lpyl in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Loncastuximab tesirine-lpyl in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Loncastuximab tesirine-lpyl FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Loncastuximab tesirine-lpyl in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Loncastuximab tesirine-lpyl in pediatric patients.

Contraindications

There is limited information regarding Loncastuximab tesirine-lpyl Contraindications in the drug label.

Warnings

There is limited information regarding Loncastuximab tesirine-lpyl Warnings' in the drug label.

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Loncastuximab tesirine-lpyl Clinical Trials Experience in the drug label.

Postmarketing Experience

There is limited information regarding Loncastuximab tesirine-lpyl Postmarketing Experience in the drug label.

Drug Interactions

There is limited information regarding Loncastuximab tesirine-lpyl Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Loncastuximab tesirine-lpyl in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Loncastuximab tesirine-lpyl in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Loncastuximab tesirine-lpyl during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Loncastuximab tesirine-lpyl in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Loncastuximab tesirine-lpyl in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Loncastuximab tesirine-lpyl in geriatric settings.

Gender

There is no FDA guidance on the use of Loncastuximab tesirine-lpyl with respect to specific gender populations.

Race

There is no FDA guidance on the use of Loncastuximab tesirine-lpyl with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Loncastuximab tesirine-lpyl in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Loncastuximab tesirine-lpyl in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Loncastuximab tesirine-lpyl in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Loncastuximab tesirine-lpyl in patients who are immunocompromised.

Immunogenicity

• As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies to loncastuximab tesirine-lpyl in other studies or to other products may be misleading.

• In LOTIS-2, 0 of 134 patients tested positive for antibodies against loncastuximab tesirine-lpyl after treatment. The potential effect of anti-drug antibodies to ZYNLONTA on pharmacokinetics, efficacy, or safety is unknown.

Administration and Monitoring

Administration

There is limited information regarding Loncastuximab tesirine-lpyl Administration in the drug label.

Monitoring

There is limited information regarding Loncastuximab tesirine-lpyl Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Loncastuximab tesirine-lpyl and IV administrations.

Overdosage

There is limited information regarding Loncastuximab tesirine-lpyl overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Loncastuximab tesirine-lpyl Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Loncastuximab tesirine-lpyl Mechanism of Action in the drug label.

Structure

There is limited information regarding Loncastuximab tesirine-lpyl Structure in the drug label.

Pharmacodynamics

There is limited information regarding Loncastuximab tesirine-lpyl Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Loncastuximab tesirine-lpyl Pharmacokinetics in the drug label.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

• Carcinogenicity studies have not been conducted with loncastuximab tesirine-lpyl or SG3199.

• SG3199 was genotoxic in an in vitro micronucleus test and a chromosome aberration assay using human lymphocytes through a clastogenic mechanism. These results are consistent with the pharmacological effect of SG3199 as a covalent DNA crosslinking agent. Results of a bacterial reverse mutation assay (Ames test) were inconclusive due to cytotoxicity.

• Fertility studies have not been conducted with loncastuximab tesirine-lpyl. Results from repeat-dose toxicity studies with intravenous administration of loncastuximab tesirine-lpyl in cynomolgus monkeys indicate the potential for impaired male reproductive function and fertility. Administration of loncastuximab tesirine-lpyl to cynomolgus monkeys every 3 weeks at 0.6 mg/kg for a total of 2 doses, or every 3 weeks at 0.3 mg/kg for 13 weeks resulted in adverse findings that included decreased weight and/or size of the testes and epididymis, atrophy of the seminiferous tubules, germ cell degeneration, and/or reduced sperm content. The dose of 0.3 mg/kg in animals results in an exposure (AUC) that is approximately 3 times the exposure at the maximum recommended human dose [MRHD] of 0.15 mg/kg. Findings were not reversible at the end of the 12-week recovery period following 4 or 13 weeks of dosing.

Animal Toxicology and/or Pharmacology

• Inflammatory-mediated toxicities associated with PBDs have been observed at low incidence in animals. In repeat-dose toxicity studies in cynomolgus monkeys, administration of loncastuximab tesirine-lpyl was associated with potential inflammatory mediated-toxicities, including in the lungs and kidneys.
• Renal toxicity including increased kidney weights and nephropathy with variable inflammation and fibrosis that was reversible was observed in monkeys. Black skin spots potentially related to phototoxicity were observed and were still present after the 12-week treatment-free period.

Clinical Studies

Relapsed or Refractory Diffuse Large B-cell Lymphoma

• The efficacy of ZYNLONTA was evaluated in LOTIS-2 (NCT03589469), an open-label, single-arm trial in 145 adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after at least 2 prior systemic regimens. The trial excluded patients with bulky disease and active central nervous system lymphoma. Patients received ZYNLONTA 0.15 mg/kg every 3 weeks for 2 cycles, then 0.075 mg/kg every 3 weeks for subsequent cycles and received treatment until progressive disease, or unacceptable toxicity.
• Of the 145 patients enrolled, the median age was 66 years (range 23 to 94), 59% male, and 94% had an ECOG performance status of 0 to 1. Race was reported in 97% of patients; of these patients, 90% were White, 3% were Black, and 2% were Asian. The diagnosis was DLBCL not otherwise specified (NOS) in 88% (including 20% with DLBCL arising from low-grade lymphoma) and high-grade B-cell lymphoma in 7%. The median number of prior therapies was 3 (range 2 to 7), 63% with refractory disease, 17% with prior stem cell transplant, and 9% with prior chimeric antigen receptor (CAR) T-cell therapy.
• Efficacy was established on the basis of overall response rate (ORR) as assessed by an Independent Review Committee (IRC) using Lugano 2014 criteria (Table 4). The median follow-up time was 7.3 months (range 0.3 to 20.2).

Efficacy Results in Patients with Relapsed or Refractory DLBCL

The median time to response was 1.3 months (range 1.1 to 8.1).

How Supplied

ZYNLONTA (loncastuximab tesirine-lpyl) for injection is a sterile, preservative-free, white to off-white lyophilized powder, which has a cake-like appearance, supplied in a single-dose vial for reconstitution and further dilution. Each carton (NDC 79952-110-01) contains one 10 mg single-dose vial.

Storage

• Store refrigerated at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not use beyond the expiration date shown on the carton. Do not freeze. Do not shake.

Special Handling

• ZYNLONTA is a hazardous drug. Follow applicable special handling and disposal procedures.1

Any unused drug product or waste material should be disposed in accordance with local requirements.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Loncastuximab tesirine-lpyl Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Loncastuximab tesirine-lpyl interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Loncastuximab tesirine-lpyl Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Loncastuximab tesirine-lpyl Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.