ZYNLONTA loncastuximab tesirine 10 mg/2mL Injection, Powder, Lyophilized, For Solution
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Other monoclonal antibodies and antibody drug conjugates class.
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🏭 Manufacturer & labeler
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🩺 Clinical
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $7,002.27 | $14,004.53 / 2 ml |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · J9359 | $226.608 / J9359 unit | — |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Zynlonta 10 mg/2mLthis 79952-0110-01 | ADC | 1 vial | — | — | FDA listed | — |
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⏳ Availability & biosimilar status
Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.
Why the date isn’t exact: Biosimilar timing can change because patents may be challenged, settled, licensed, added or removed, and litigation can move the real date earlier or later.
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- Biologic patent
- A patent the reference product’s maker has publicly listed. A biosimilar generally can’t launch until these expire — unless they’re invalidated or resolved in a settlement.
- Reference-product exclusivity
- A flat 12 years of FDA market protection from the biologic’s first licensure (the BPCIA). No biosimilar can be licensed before it ends, regardless of patents.
- Interchangeable exclusivity
- The first interchangeable biosimilar can earn a period as the only interchangeable version (pharmacists can substitute it without the prescriber).
- Earliest biosimilar (LOE)
- The latest of all the dates above — the soonest a biosimilar can realistically reach the market. Litigation and settlements can move it earlier.
Biologics have no small-molecule “generics” — competition comes from FDA-licensed biosimilars, tracked in the FDA Purple Book.
| Code | What it grants | Expires |
|---|---|---|
| RefProduct | Reference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this date | Apr 23, 2033 |
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🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2025 (Q1-Q4)
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 79952-0110-01 You're viewing this | 1 VIAL, SINGLE-DOSE in 1 CARTON (79952-110-01) / 2 mL in 1 VIAL, SINGLE-DOSE | 2021-04-30 | Active |
🧭 About this NDC listing & data coverage
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | — Not published for this NDC No photo available yet for this listing. |
| Inactive ingredients (structured) | — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available. |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | ✓ Available |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
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 )
⏱️ Dosage and Administration ▾
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 )
2.1Recommended 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.
2.2Recommended 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.
2.3Dosage 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.
2.4Reconstitution 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, c…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS For Injection: 10 mg of loncastuximab tesirine-lpyl as a white to off-white lyophilized powder in a single-dose vial for reconstitution and further dilution. For injection: 10 mg of loncastuximab tesirine-lpyl as a lyophilized powder in a single-dose vial for reconstitution and further dilution. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Effusion and Edema, Including Capillary Leak Syndrome : Monitor for the development of pleural effusion, pericardial effusion, ascites, peripheral edema, and general edema. Consider diagnostic imaging when symptoms develop or worsen. ( 5.1 ) Myelosuppression: Monitor blood cell counts.
Withhold, reduce, or discontinue ZYNLONTA based on severity. ( 5.2 ) Infections : Monitor for infection and treat promptly. ( 5.3 ) Hepatotoxicity, Including Drug-Induced Liver Injury : Monitor liver function tests during treatment.
Withhold or permanently discontinue ZYNLONTA based on severity. ( 5.4 ) Cutaneous Reaction s: Monitor patients for new or worsening cutaneous reactions, including photosensitivity reactions. Dermatologic consultation should be considered.
( 5.5 ) Embryo-Fetal Toxic ity: Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception. ( 5.6 , 8.1 , 8.3 )
5.1Effusion and Edema, Including Capillary Leak Syndrome Serious effusion and edema, including capillary leak syndrome, occurred in patients treated with ZYNLONTA. Grade 3 edema occurred in 3% (primarily peripheral edema or ascites) and Grade 3 pleural effusion occurred in 3%, and Grade 3 or 4 pericardial effusion occurred in 1% [see Adverse Reactions (6.1) ] . Rare cases of cardiac tamponade have been reported in patients with Grade 3 or 4 pericardial effusion.
Grade 3 or higher capillary leak syndrome occurred in 0.6%. Monitor patients for new or worsening edema or effusions. Consider diagnostic imaging in patients who develop symptoms of pleural effusion or pericardial effusion, such as new or worsened dyspnea, chest pain, and/or ascites such as swelling in the abdomen and bloating.
Institute appropriate medical management for edema or effusions. Evaluate and institute appropriate medical management for capillary leak syndrome in patients experiencing worsening effusion or edema, with signs and symptoms of weight gain, severe hypotension, hypoalbuminemia, and/or hemoconcentration (by elevated hemoglobin/hematocrit, etc.). Withhold or discontinue ZYNLONTA based on severity [see Dosage and Administration (2.3) ] .
5.2Myelosuppression Treatment with ZYNLONTA can cause serious or severe myelosuppression, including neutropenia, thrombocytopenia, and anemia. Grade 3 or 4 neutropenia occurred in 32%, thrombocytopenia in 20%, and anemia in 12% of patients. Grade 4 neutropenia occurred in 21% and thrombocytopenia in 7% of patients.
Febrile neutropenia occurred in 3% [see Adverse Reactions (6.1) ]. Monitor complete blood counts throughout treatment. Cytopenias may require interruption, dose reduction, or discontinuation of ZYNLONTA.
Consider prophylactic granulocyte colony-stimulating factor administration as applicable [see Dosage and Administration (2.3) ].
5.3Infections Fatal and serious infections, including opportunistic infections, occurred in patients treated with ZYNLONTA. Grade 3 or higher infections occurred in 10% of patients, with fatal infections occurring in 2%. The most frequent Grade ≥3 infections included sepsis and pneumonia [see Adverse Reactions (6.1) ] .
Monitor for any new or worsening signs or symptoms consistent with infection. For Grade 3 or 4 infection, withhold ZYNLONTA until infection has resolved [see Dosage and Administration (2.3) ] .
5.4Hepatotoxicity, Including Drug-Induced Liver Injury Cholestatic and hepatocellular liver injury, including severe, life-threatening, and fatal cases of drug-induced liver injury (DILI), have occurred in patients treated with ZYNLONTA. Monitor liver function tests at baseline and throughout treatment with ZYNLONTA. In the event of suspected DILI or Grade ≥3 increase in ALT or AST, withhold ZYNLONTA until toxicity resolves to Grade 1 or lower.
Upon confirmation of DILI, discontinue ZYNLONTA. [see Dosage and Administration (2.3) ] . ZYNLONTA should be avoided in patients with severe hepatic impairment [see Clinical Pharmacology (8.6 , 12.3) ]…
🤒 Adverse Reactions ▾
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 .
6.1Clinical 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, thrombocyto…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 ) Severe Hepatic Impairment: Avoid use of ZYNLONTA. ( 8.6 )
8.1Pregnancy Risk Summary Based on its mechanism of action, ZYNLONTA can cause embryo-fetal harm when administered to a pregnant woman, because it contains a genotoxic compound (SG3199) and affects actively dividing cells [see Clinical Pharmacology (12.1) and Nonclinical Toxicology (13.1) ] . There are no available data on the use of ZYNLONTA in pregnant women to evaluate for drug-associated risk. No animal reproduction studies were conducted with ZYNLONTA.
Advise pregnant women of the potential risk to a fetus . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Animal reproductive or developmental toxicity studies were not conducted with loncastuximab tesirine-lpyl. The cytotoxic component of ZYNLONTA, SG3199, crosslinks DNA, is genotoxic, and is toxic to rapidly dividing cells, suggesting it has the potential to cause embryotoxicity and teratogenicity.
8.2Lactation Risk Summary There is no data on the presence of loncastuximab tesirine-lpyl or SG3199 in human milk, the effects on the breastfed child, or milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with ZYNLONTA and for 3 months after the last dose.
8.3Females and Males of Reproductive Potential ZYNLONTA can cause fetal harm when administered to pregnant women [see Use in Specific Populations (8.1) ] . Pregnancy Testing Pregnancy testing is recommended for females of reproductive potential prior to initiating ZYNLONTA. Contraception Females Advise women of reproductive potential to use effective contraception during treatment and for 10 months after the last dose.
Males Because of the potential for genotoxicity, advise males with female partners of reproductive potential to use effective contraception during the treatment with ZYNLONTA and for 7 months after the last dose [see Nonclinical Toxicology (13.1) ] . Infertility Males Based on the results from animal studies, ZYNLONTA may impair fertility in males. The effects were not reversible in male cynomolgus monkeys during the 12-week drug-free period [see Nonclinical Toxicology (13.1) ] .
8.4Pediatric Use Safety and effectiveness of ZYNLONTA in pediatric patients have not been established.
8.5Geriatric Use Of the 145 patients with large B-cell lymphoma who received ZYNLONTA in clinical trials, 55% were 65 years of age and older, while 14% were 75 years of age and older [see Clinical Studies (14.1) ] . No overall differences in safety or effectiveness were observed between these patients and younger patients.
8.6Hepatic Impairment No dose adjustment is recommended for patients with mild hepatic impairment (total bilirubin ≤ upper limit of normal [ULN] and aspartate aminotransferase (AST) > ULN or total bilirubin > 1 to 1.5 × ULN and any AST). Monitor patients with mild hepatic impairment for potential increased incidence of adverse reactions and modify the ZYNLONTA dosage in the event of adverse reactions [see Dosage and Administration (2.3) ] . There is limited safety information available in patients with moderate hepatic impairment.
ZYNLONTA should be avoided in patients with severe hepatic impairment [see Clinical Pharmacology (12.3) ] .
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Based on its mechanism of action, ZYNLONTA can cause embryo-fetal harm when administered to a pregnant woman, because it contains a genotoxic compound (SG3199) and affects actively dividing cells [see Clinical Pharmacology (12.1) and Nonclinical Toxicology (13.1) ] . There are no available data on the use of ZYNLONTA in pregnant women to evaluate for drug-associated risk. No animal reproduction studies were conducted with ZYNLONTA.
Advise pregnant women of the potential risk to a fetus . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Animal reproductive or developmental toxicity studies were not conducted with loncastuximab tesirine-lpyl. The cytotoxic component of ZYNLONTA, SG3199, crosslinks DNA, is genotoxic, and is toxic to rapidly dividing cells, suggesting it has the potential to cause embryotoxicity and teratogenicity.
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness of ZYNLONTA in pediatric patients have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use Of the 145 patients with large B-cell lymphoma who received ZYNLONTA in clinical trials, 55% were 65 years of age and older, while 14% were 75 years of age and older [see Clinical Studies (14.1) ] . No overall differences in safety or effectiveness were observed between these patients and younger patients.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Loncastuximab tesirine-lpyl is an antibody-drug conjugate (ADC) targeting CD19. The monoclonal IgG1 kappa antibody component binds to human CD19, a transmembrane protein expressed on the surface of cells of B-lineage origin. The small molecule component is SG3199, a PBD dimer and alkylating agent.
Upon binding to CD19, loncastuximab tesirine-lpyl is internalized followed by release of SG3199 via proteolytic cleavage. The released SG3199 binds to the DNA minor groove and forms highly cytotoxic DNA interstrand crosslinks, subsequently inducing cell death. Loncastuximab tesirine-lpyl had anticancer activity in animal models of lymphoma.
12.2Pharmacodynamics Higher loncastuximab tesirine-lpyl exposure in Cycle 1 was associated with higher incidence of some Grade ≥2 adverse reactions, including skin and nail reactions, liver function test abnormalities and increased gamma-glutamyltransferase. Lower loncastuximab tesirine-lpyl exposure in Cycle 1 was associated with lower efficacy over the dose range of 0.015-0.2 mg/kg (0.1 to 1.33 times the maximum recommended dose). Cardiac Electrophysiology At the maximum recommended therapeutic dose of 0.15 mg/kg during Cycle 1 and Cycle 2, loncastuximab tesirine-lpyl does not cause large mean increases (i.e., >20 msec) in the QTc interval.
12.3Pharmacokinetics The exposure of loncastuximab tesirine-lpyl at the approved recommended dosage in Cycle 2 and at steady state is shown in Table 4. Loncastuximab tesirine-lpyl steady state C max was 28.2% lower than the C max after the first dose. The time to reach steady state was 105 days.
Table 4: Loncastuximab Tesirine-lpyl Exposure Parameters Data presented as mean and coefficient of variation (CV %) Time C max (ng/mL) AUC tau (ng ∙ day/mL) C max = Maximum observed serum concentration; AUC tau = Area under curve over the dosing interval Cycle 2 2,911 (35.3%) 21,665 (54.1%) Steady state 1,776 (32.1%) 16,882 (38.2%) Distribution The mean (CV%) of loncastuximab tesirine-lpyl volume of distribution was 7.11 (26.6%) L. Elimination The mean (CV%) of loncastuximab tesirine-lpyl clearance decreased with time from 0.499 L/day (89.3%) after a single dose to 0.275 L/day (38.2%) at steady state.
The mean (standard deviation) half-life of loncastuximab tesirine-lpyl was 20.8 (7.06) days at steady state. Metabolism The monoclonal antibody portion of loncastuximab tesirine-lpyl is expected to be metabolized into small peptides by catabolic pathways. The small molecule cytotoxin, SG3199, is metabolized by CYP3A4/5 in vitro.
Excretion The major excretion pathways of SG3199 have not been studied in humans. SG3199 is expected to be minimally renally excreted. Specific Populations No clinically significant differences in the pharmacokinetics of loncastuximab tesirine-lpyl were observed based on age (20-94 years), sex, race (White vs.
Black), body weight (42.1 to 160.5 kg), ECOG status (0 to 2) or mild to moderate renal impairment (CLcr 30 to <90 mL/min using the Cockcroft-Gault equation). The effect of severe renal impairment (CLcr 15 to 29 mL/min), and end-stage renal disease with or without hemodialysis on loncastuximab tesirine-lpyl pharmacokinetics is unknown. Patients with Hepatic Impairment Mild hepatic impairment (total bilirubin ≤ ULN and AST > ULN, or total bilirubin >1 to 1.5 × ULN and any AST) may increase the exposure of unconjugated SG3199, however there was no clinically significant effect on loncastuximab tesirine-lpyl pharmacokinetics.
There is insufficient data in patients with moderate (total bilirubin >1.5 to ≤3 × ULN and any AST) hepatic impairment or severe (total bilirubin >3 ULN and any AST) hepatic impairment. Drug Interaction Studies In Vitro Studies Cytochrome P450 (CYP) Enzymes: SG3199 does not inhibit CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4/5 at clinically relevant unconjugated SG3199 concentrations. Transporter Systems: SG3199 is a substrate of P-glycoprot…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Loncastuximab tesirine-lpyl is an antibody-drug conjugate (ADC) targeting CD19. The monoclonal IgG1 kappa antibody component binds to human CD19, a transmembrane protein expressed on the surface of cells of B-lineage origin. The small molecule component is SG3199, a PBD dimer and alkylating agent.
Upon binding to CD19, loncastuximab tesirine-lpyl is internalized followed by release of SG3199 via proteolytic cleavage. The released SG3199 binds to the DNA minor groove and forms highly cytotoxic DNA interstrand crosslinks, subsequently inducing cell death. Loncastuximab tesirine-lpyl had anticancer activity in animal models of lymphoma.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING 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 and Handling 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.
📦 Storage and Handling ▾
Storage and Handling 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.
📋 Description ▾
11 DESCRIPTION Loncastuximab tesirine-lpyl is a CD19-directed antibody and alkylating agent conjugate, consisting of a humanized IgG1 kappa monoclonal antibody conjugated to SG3199, a pyrrolobenzodiazepine (PBD) dimer cytotoxic alkylating agent, through a protease-cleavable valine-alanine linker. SG3199 attached to the linker is designated as SG3249, also known as tesirine. Loncastuximab tesirine-lpyl has an approximate molecular weight of 151 kDa.
An average of 2.3 molecules of SG3249 are attached to each antibody molecule. Loncastuximab tesirine-lpyl is produced by chemical conjugation of the antibody and small molecule components. The antibody is produced by mammalian (Chinese hamster ovary) cells, and the small molecule components are produced by chemical synthesis.
ZYNLONTA (loncastuximab tesirine-lpyl) for injection is supplied as a sterile, white to off-white, preservative-free, lyophilized powder, which has a cake-like appearance, for intravenous infusion after reconstitution and dilution. Each single-dose vial delivers 10 mg of loncastuximab tesirine-lpyl, L-histidine (2.8 mg), L-histidine monohydrochloride (4.6 mg), polysorbate 20 (0.4 mg), and sucrose (119.8 mg). After reconstitution with 2.2 mL Sterile Water for Injection, USP, the final concentration is 5 mg/mL with a pH of approximately 6.0.
Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Effusion and Edema, Including Capillary Leak Syndrome : Advise patients to contact their healthcare provider if they experience swelling, rapid weight gain, shortness of breath, worsening malaise, dizziness, or difficult, labored breathing. [see Warnings and Precautions (5.1)] . Myelosuppression : Advise patients to immediately contact their healthcare provider for a fever of 100.4°F (38°C) or greater, or signs or symptoms of bruising or bleeding.
Advise patients of the need for periodic monitoring of blood counts [see Warnings and Precautions (5.2) ] . Infections : Advise patients to immediately contact their healthcare provider for signs or symptoms of infection, including fever, chills, weakness and/or difficulty breathing [see Warnings and Precautions (5.3) ] . Hepatotoxicity, Including Drug-Induced Liver Injury : Inform patients that liver problems, including drug-induced liver injury and abnormalities in liver tests, may develop during ZYNLONTA treatment.
Advise patients that they will need monitoring of their liver through regular blood testing throughout their treatment. Advise patients to contact their healthcare provider immediately if they experience abdominal discomfort, pruritus, dark urine, or jaundice. [see Warnings and Precautions (5.4) ] . Cutaneous Reactions : Advise patients that skin reaction or rash can occur.
Patients should be directed to minimize or avoid exposure to direct natural or artificial sunlight, including sunlight exposure through glass windows. Patients should be instructed to protect skin from exposure to sunlight by wearing sun-protective clothing and/or the use of sunscreen products [see Warnings and Precautions (5.5) ]. Embryo-Fetal Toxicity : - Advise pregnant women of the potential risk to a fetus.
Advise female patients of reproductive potential to contact their healthcare provider if they become pregnant, or if pregnancy is suspected, during treatment with ZYNLONTA [see Use in Specific Populations (8.1) ]. - Advise women of reproductive potential to use effective contraception during treatment with ZYNLONTA and for 10 months after the last dose. - Advise male patients with female partners of reproductive potential, to use effective contraception during treatment with ZYNLONTA and for 7 months after the last dose [see Warnings and Precautions (5.6) and Use in Specific Populations (8.1) , (8.3) ] .
Lactation : Advise women not to breastfeed during treatment with ZYNLONTA and for 3 months after the last dose [see Use in Specific Populations (8.2) ].