ZYNLONTA

ZYNLONTA is an FDA-registered drug product whose active ingredient is LONCASTUXIMAB TESIRINE. It is labelled by ADC Therapeutics America, Inc. taken by intravenous and marketed as a human prescription drug product. Identifiers on file: NDC 79952-110, application BLA761196, label effective 20260612. This page reproduces the FDA-approved label text so you can check what a product is, who makes it and how it is supplied before discussing it with a pharmacist or prescriber.

Across FDA labelling, products containing LONCASTUXIMAB TESIRINE are most often described in connection with: b-cell lymphoma, treatment adult, relapsed refractory, lines systemic, therapy including, diffuse large, otherwise specified, dlbcl arising. Wording differs between labels, and the full indications section on this page takes precedence when it is present.

1 INDICATIONS AND USAGE ZYNLONTA is indicated 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. This indication is approved under accelerated approval based on overall response rate [see Clinical Studies (14.1) ] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). ZYNLONTA is a CD19-directed antibody and alkylating agent conjugate indicated 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. ( 1 ) This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). ( 1 )

2 DOSAGE AND ADMINISTRATION ZYNLONTA is an intravenous infusion over 30 minutes on Day 1 of each cycle (every 3 weeks). The recommended dosage is: 0.15 mg/kg every 3 weeks for 2 cycles. 0.075 mg/kg every 3 weeks for subsequent cycles. ( 2.1 ) Premedicate with dexamethasone 4 mg orally or intravenously twice daily for 3 days beginning the day before ZYNLONTA. ( 2.2 ) See Full Prescribing Information for instructions on preparation and administration. ( 2.4 ) 2.1 Recommended Dosage ZYNLONTA as an intravenous infusion administered over 30 minutes on Day 1 of each cycle (every 3 weeks). Administer intravenous infusion as follows: 0.15 mg/kg every 3 weeks for 2 cycles. 0.075 mg/kg every 3 weeks for subsequent cycles. 2.2 Recommended Premedication Unless contraindicated, administer dexamethasone 4 mg orally or intravenously twice daily for 3 days beginning the day before administering ZYNLONTA. If dexamethasone administration does not begin the day before ZYNLONTA, dexamethasone should begin at least 2 hours prior to administration of ZYNLONTA. 2.3 Dosage Modifications and Delays Table 1: Recommended Dosage Modifications for Adverse Reactions Adverse Reactions Severity Dosage Modification Hematologic Adverse Reactions Neutropenia [see Warnings and Precautions (5.2) ] Absolute neutrophil count less than 1 × 10 9 /L Withhold ZYNLONTA until neutrophil counts returns to 1 × 10 9 /L or higher Thrombocytopenia [see Warnings and Precautions (5.2) ] Platelet count less than 50,000/mcL Withhold ZYNLONTA until platelet count returns to 50,000/mcL or higher Nonhematologic Adverse Reactions Edema or Effusion [see Warnings and Precautions (5.1) ] Grade 2 National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 or higher Withhold ZYNLONTA until the toxicity resolves to Grade 1 or less Pericardial Effusion [see Warnings and Precautions (5.1) ] Grade 2 Withhold ZYNLONTA until the toxicity resolves. Discontinue ZYNLONTA if effusion recurs Grade 3 or higher Discontinue ZYNLONTA Hepatotoxicity [ see Warnings and Precautions (5.4) ] Grade 3 or higher increase in AST or ALT or suspected DILI Withhold ZYNLONTA until toxicity resolves to Grade 1 or less, discontinue for confirmed DILI Other Adverse Reactions [see Warnings and Precautions (5.3) , (5.5) , Adverse Reactions (6.1) ] Grade 3 or higher Withhold ZYNLONTA until the toxicity resolves to Grade 1 or less Recommendations for Dosage Delays If dosing is delayed by more than 3 weeks due to toxicity related to ZYNLONTA, reduce subsequent doses by 50%. If toxicity reoccurs following dose reduction, consider discontinuation. Note: If toxicity requires dose reduction following the second dose of 0.15 mg/kg (Cycle 2), the patient should receive the dose of 0.075 mg/kg for Cycle 3. 2.4 Reconstitution and Administration Instructions Reconstitute and further dilute ZYNLONTA prior to intravenous infusion. Use appropriate aseptic technique. ZYNLONTA is a hazardous drug. Follow applicable special handling and disposal procedures. 1 Dose calculation Calculate the total dose (mg) required based on the patient's weight and prescribed dose [see Dosage and Administration (2.1) ] . For patients with a body mass index (BMI) ≥35 kg/m 2 , calculate the dose based on an adjusted body weight (ABW) as follows: ABW in kg = 35 kg/m 2 × (height in meters) 2 More than one vial may be needed to achieve the calculated dose. Convert the calculated dose (mg) to volume using 5 mg/mL, which is the concentration of ZYNLONTA after reconstitution. Reconstitution of lyophilized ZYNLONTA Reconstitute each ZYNLONTA vial using 2.2 mL of Sterile Water for Injection, USP with the stream directed toward the inside wall of the vial to obtain a final concentration of 5 mg/mL. Swirl the vial gently until the powder is completely dissolved. Do not shake . Do not expose to direct sunlight. Inspect the reconstituted solution for particulate matter and discoloration. The solution should appear clear to slightly opalescent, colorless to slightly yellow. Do not use if the reconstituted solution is discolored, is cloudy, or contains visible particulates. Use reconstituted ZYNLONTA immediately. If not used immediately, store the reconstituted solution in the vial for up to 4 hours refrigerated at 2°C to 8°C (36°F to 46°F) or room temperature 20°C to 25°C (68°F to 77°F). Do not freeze . The product does not contain a preservative. Discard unused vial after reconstitution if the recommended storage time is exceeded. Dilution in infusion bag Withdraw the required volume of reconstituted solution from the ZYNLONTA vial using a sterile syringe. Discard any unused portion left in the vial. Add the calculated dose volume of ZYNLONTA solution into a 50 mL infusion bag of 5% Dextrose Injection, USP . Gently mix the intravenous bag by slowly inverting the bag. Do not shake . If not used immediately, store the diluted ZYNLONTA infusion solution refrigerated at 2°C to 8°C (36°F to 46°F) for up to 24 hours or at room temperature 20°C to 25°C (68°F to 77°F) for up to 8 hours. Discard diluted infusion bag if storage time exceeds these limits. Do not freeze. No incompatibilities have been observed between ZYNLONTA and intravenous infusion bags with product-contacting materials of polyvinylchloride (PVC), polyolefin (PO), and PAB ® (copolymer of ethylene and propylene). Administration Administer by intravenous infusion over 30 minutes using a dedicated infusion line equipped with a sterile, non-pyrogenic, low-protein binding in-line or add-on filter (0.2- or 0.22-micron pore size) and catheter. Extravasation of ZYNLONTA has been associated with irritation, swelling, pain, and/or tissue damage, which may be severe [see Adverse Reactions (6.1) ] . Monitor the infusion site for possible subcutaneous infiltration during drug administration. Do not mix ZYNLONTA with or administer as an infusion with other drugs.

4 CONTRAINDICATIONS None. None. ( 4 )

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Effusion and Edema [see Warnings and Precautions (5.1) ] Myelosuppression [see Warnings and Precautions (5.2)] Infections [see Warnings and Precautions (5.3) ] Hepatotoxicity, including DILI [see Warnings and Precautions(5.4) ] Cutaneous Reactions [see Warnings and Precautions (5.5) ] Most common (≥20%) adverse reactions, including laboratory abnormalities, are thrombocytopenia, increased gamma-glutamyltransferase, neutropenia, anemia, hyperglycemia, transaminase elevation, fatigue, hypoalbuminemia, rash, edema, nausea, and musculoskeletal pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact ADC Therapeutics at 1-855-690-0340 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 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 the WARNINGS AND PRECAUTIONS reflect exposure to ZYNLONTA as a single agent at an initial dose of 0.15 mg/kg in 215 patients with DLBCL in studies ADCT-402-201 (LOTIS-2) and ADCT-402-101, which includes 145 patients from LOTIS-2 treated with 0.15 mg/kg × 2 cycles followed by 0.075 mg/kg for subsequent cycles. Among 215 patients who received ZYNLONTA, the median number of cycles was 3 (range 1 to 15) with 58% receiving three or more cycles and 30% receiving five or more cycles. In this pooled safety population of 215 patients, the most common (>20%) adverse reactions, including laboratory abnormalities, were thrombocytopenia, increased gamma-glutamyltransferase, neutropenia, anemia, hyperglycemia, transaminase elevation, fatigue, hypoalbuminemia, rash, edema, nausea, and musculoskeletal pain. Relapsed or Refractory Diffuse Large B-Cell Lymphoma LOTIS-2 The safety of ZYNLONTA was evaluated in LOTIS-2, an open-label, single-arm clinical trial that enrolled 145 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), including high-grade B-cell lymphoma, after at least two prior systemic therapies [see Clinical Studies (14.1) ] . The trial required hepatic transaminases, including gamma-glutamyltransferase (GGT), ≤2.5 times upper limit of normal (ULN), total bilirubin ≤1.5 times ULN, and creatinine clearance ≥60 mL/min. 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. Among the 145 patients, the median number of cycles received was 3, with 34% receiving 5 or more cycles. The median age was 66 years (range 23 to 94), 59% were male, and 94% had an Eastern Cooperative Oncology Group (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. Serious adverse reactions occurred in 28% of patients receiving ZYNLONTA. The most common serious adverse reactions that occurred in ≥2% receiving ZYNLONTA were febrile neutropenia, pneumonia, edema, pleural effusion, and sepsis. Fatal adverse reactions occurred in 1%, due to infection. Permanent treatment discontinuation due to an adverse reaction of ZYNLONTA occurred in 19% of patients. Adverse reactions resulting in permanent discontinuation of ZYNLONTA in ≥2% were gamma-glutamyltransferase increased, edema, and effusion. Dose reductions due to an adverse reaction of ZYNLONTA occurred in 8% of patients. Adverse reactions resulting in dose reduction of ZYNLONTA in ≥4% was gamma-glutamyltransferase increased. Dosage interruptions due to an adverse reaction occurred in 49% of patients receiving ZYNLONTA. Adverse reactions leading to interruption of ZYNLONTA in ≥5% were gamma-glutamyltransferase increased, neutropenia, thrombocytopenia, and edema. Table 2 summarizes the adverse reactions in LOTIS-2. Table 2: Adverse Reactions (≥10%) in Patients with Relapsed or Refractory DLBCL who received ZYNLONTA in LOTIS-2 Adverse Reaction ZYNLONTA (N=145) All Grades (%) Grades 3 or 4 (%) General Disorders and Administration Site Conditions Fatigue Fatigue includes fatigue, asthenia, and lethargy 38 1 No Grade 4 adverse reactions occurred Edema Edema includes edema, face edema, generalized edema, peripheral edema, ascites, fluid overload, peripheral swelling, swelling, and swelling face 28 3 Skin and Subcutaneous Tissue Disorders Rash Rash includes rash, rash erythematous, rash maculopapular, rash pruritic, rash pustular, erythema, generalized erythema, dermatitis, dermatitis acneiform, dermatitis bullous, dermatitis exfoliative generalized, and palmar-plantar erythrodysesthesia syndrome 30 2 Pruritus 12 0 Photosensitivity reaction 10 2 Gastrointestinal Disorders Nausea 23 0 Diarrhea 17 2 Abdominal pain Abdominal pain includes abdominal pain, abdominal discomfort, abdominal pain lower, and abdominal pain upper 14 3 Vomiting 13 0 Constipation 12 0 Musculoskeletal and Connective Tissue Disorders Musculoskeletal pain Musculoskeletal pain includes musculoskeletal pain, musculoskeletal chest pain, musculoskeletal discomfort, back pain, limb discomfort, myalgia, neck pain, non-cardiac chest pain, and pain in extremity 23 1 Metabolism and Nutrition Disorders Decreased appetite 15 0 Respiratory Disorders Dyspnea Dyspnea includes dyspnea, and dyspnea exertional 13 1 Pleural effusion 10 2 Infection Upper respiratory tract infection Upper respiratory tract infection includes upper respiratory tract infection, upper respiratory tract congestion, nasopharyngitis, rhinitis, rhinovirus infection, and sinusitis 10 <1 Clinically relevant adverse reactions in <10% of patients (all grades) who received ZYNLONTA included: Blood and lymphatic system disorders: Febrile neutropenia (3%) Cardiac disorders: Pericardial effusion (3%) Infections: Pneumonia Pneumonia includes pneumonia and lung infection (5%), sepsis Sepsis includes sepsis, escherichia sepsis, and septic shock (2%) Skin and subcutaneous disorders: Hyperpigmentation (4%) General disorders: Infusion site extravasation (<1%) Selected Other Adverse Reactions Inflammatory-related conditions were reported in 3% of patients in LOTIS-2, including pericarditis, pneumonitis, pleuritis, and dermatitis. Table 3 summarizes the laboratory abnormalities in LOTIS-2. Table 3: Select Laboratory Abnormalities (≥10%) That Worsened from Baseline in Patients with Relapsed or Refractory DLBCL Who Received ZYNLONTA in LOTIS-2 Laboratory Abnormality ZYNLONTA The denominator used to calculate the rate varied from 143 to 145 based on the number of patients with a baseline value and at least one post-treatment value All Grades (%) Grade 3 or 4 (%) Hematologic Platelets decreased 58 17 Neutrophils decreased 52 30 Hemoglobin decreased 51 10 No Grade 4 adverse reactions occurred Chemistry GGT increased 57 21 Glucose increased 48 8 AST increased 41 <1 Albumin decreased 37 <1 ALT increased 34 3 Other Clinical Trials Experience The following adverse reactions have been reported following administration of ZYNLONTA: Hepatotoxicity, including drug- induced liver injury (DILI). 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of ZYNLONTA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Skin and Subcutaneous Tissue Disorders: Telangiectasia, including cutaneous collagenous vasculopathy, blister, rash vesicular.

What is ZYNLONTA used for?
1 INDICATIONS AND USAGE ZYNLONTA is indicated 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. This indication is approved under accelerated approval based on overall …

Who makes ZYNLONTA?
ADC Therapeutics America, Inc. is the labeler of record for ZYNLONTA.

What form does ZYNLONTA come in?
administered by intravenous. Strengths and pack sizes vary by label, so compare the NDC on your pack with the identifier listed on this page.

Is ZYNLONTA prescription or over-the-counter?
The FDA label for this product is recorded as human prescription drug. Marketing status can differ between strengths and countries, so check the dispensing rules where you live.

Has ZYNLONTA been recalled?
No FDA recall record in our database matches this product name or manufacturer. Recall data is updated periodically, so a very recent notice may not appear here yet.

Where does this information come from?
All content is reproduced from FDA Structured Product Labelling data via openFDA. It is provided for identification and reference only and is not medical advice.