Loncastuximab Tesirine

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.

• 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) ] .ICD-10: C85.90

• None. None.contraindicated

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.

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 ) 5.1 Effusion 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.

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.

Lactation: Advise not to breastfeed. ( 8.2 ) Severe Hepatic Impairment: Avoid use of ZYNLONTA. ( 8.6 ) 8.1 Pregnancy 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.

Metabolism

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.

• Apr 23, 2021BLABLA761196Adc Therapeutics Sa

1. 1Death4312%
2. 2Rash308.5%
3. 3Disease Progression288.0%
4. 4Pleural Effusion236.6%
5. 5Fatigue216.0%
6. 6Photosensitivity Reaction185.1%
7. 7Neutropenia174.8%
8. 8Thrombocytopenia144.0%
9. 9Anaemia133.7%
10. 10Covid-19133.7%
11. 11Oedema133.7%
12. 12Pneumonia133.7%
13. 13Diffuse Large B-cell Lymphoma102.8%
14. 14Oedema Peripheral102.8%
15. 15Infection92.6%

The 10 most recently updated of 37 ClinicalTrials.gov registrations naming Loncastuximab Tesirine as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study to Evaluate the Safety and Anti-cancer Activity of Loncastuximab Tesirine in Combination With Other Anti-cancer Agents in Participants With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (LOTIS-7)
  Recruiting · Phase 1 · Interventional · 200 enrolled · ADC Therapeutics S.A.
  NCT04970901updated 2026-06-09
• A Study of MT-2111 in Patients With Relapsed/Refractory DLBCL
  Active not recruiting · Phase 1 · Phase 2 · Interventional · 46 enrolled · Tanabe Pharma Corporation
  NCT05658562updated 2026-06-09
• Loncastuximab Tesirine and Venetoclax for Relapsed/ Refractory Non-Hodgkin Lymphoma
  Active not recruiting · Phase 1 · Interventional · 23 enrolled · Paolo Caimi, MD
  NCT05053659updated 2026-06-05
• Loncastuximab Tesirine and Rituximab as Bridging Therapy Before Standard-of-care CAR-T Therapy in Patients With Large B-cell Lymphoma (CORAL)
  Recruiting · Phase 2 · Interventional · 29 enrolled · University of Utah
  NCT06788964updated 2026-05-29
• A Phase II Study of Loncastuximab Tesirine as Consolidation Strategy in Patients With LBCL in PR After CAR T-cell Therapy
  Recruiting · Phase 2 · Interventional · 30 enrolled · M.D. Anderson Cancer Center
  NCT05464719updated 2026-05-20
• Loncastuximab Tesirine in WM
  Active not recruiting · Phase 2 · Interventional · 21 enrolled · Shayna Sarosiek, MD
  NCT05190705updated 2026-05-20
• Loncastuximab Tesirine and Mosunetuzumab for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma
  Recruiting · Phase 2 · Interventional · 36 enrolled · City of Hope Medical Center
  NCT05672251updated 2026-05-11
• Loncastuximab Tesirine for the Treatment of Relapsed or Refractory B-Cell Malignancies
  Recruiting · Phase 2 · Interventional · 20 enrolled · University of Washington
  NCT05453396updated 2026-05-11
• Loncastuximab Tesirine and Rituximab as First-line Therapy in Patients With Post-transplant Lymphoproliferative Disorder (PLUTO)
  Not yet recruiting · Phase 1 · Phase 2 · Interventional · 23 enrolled · University of Utah
  NCT07573436updated 2026-05-07
• Study to Evaluate Loncastuximab Tesirine With Rituximab Versus Immunochemotherapy in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
  Active not recruiting · Phase 3 · Interventional · 440 enrolled · ADC Therapeutics S.A.
  NCT04384484updated 2026-04-28

Frequently asked questions

How does Loncastuximab Tesirine work?

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.

What is Loncastuximab Tesirine used for?

According to FDA labeling, Loncastuximab Tesirine carries indications including: 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) ] .. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Loncastuximab Tesirine?

Loncastuximab Tesirine is classified as Other monoclonal antibodies and antibody drug conjugates, Alkylating Activity, CD19-directed Antibody Interactions.

What are the brand names for Loncastuximab Tesirine?

Loncastuximab Tesirine is marketed under brand names including Zynlonta.

What are the contraindications for Loncastuximab Tesirine?

Loncastuximab Tesirine labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.