Lurbinectedin

Lurbinectedin is an alkylating drug that binds guanine residues in the minor groove of DNA, forming adducts and resulting in a bending of the DNA helix towards the major groove. Adduct formation triggers a cascade of events that can affect the subsequent activity of DNA binding proteins, including some transcription factors, and DNA repair pathways, resulting in perturbation of the cell cycle and eventual cell death.

• ZEPZELCA is an alkylating drug indicated: • in combination with atezolizumab or atezolizumab and hyaluronidase-tqjs, for the maintenance treatment of adult patients with extensive-stage small cell lung cancer whose disease has not progressed after first-line induction therapy with atezolizumab or atezolizumab and hyaluronidase-tqjs, carboplatin and etoposide. ( 1.1 ) • For the treatment of adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy.ICD-10: C34.90

• None. None.contraindicated

• Recommended Dosage : 3.2 mg/m 2 administered intravenously every 21 days until disease progression or unacceptable toxicity. • Administration via a central venous line is recommended to reduce the risk of extravasation that can cause tissue necrosis requiring debridement ( 5.3 ) • Administer ZEPZELCA as an intravenous infusion over 60 minutes. • To reduce the risk of nausea, administer corticosteroids and serotonin agonists prior to Cycle 1 and consider use for subsequent cycles. ( 2.5 ) • To reduce the risk of febrile neutropenia during treatment with ZEPZELCA in combination with atezolizumab or atezolizumab and hyaluronidase-tqjs, administer granulocyte colony-stimulating factor (G-CSF) [Refer to Prescribing Information]. • Moderate Hepatic Impairment : Recommended dosage is 1.6 mg/m 2 administered intravenously every 21 days until disease progression or unacceptable toxicity. ( 2.4 , 8.6 ) • Severe Hepatic Impairment : Avoid use of ZEPZELCA. If use cannot be avoided, the recommended dosage is 1.6 mg/m 2 administered intravenously every 21 days until disease progression or unacceptable toxicity. ( 2.4 , 8.6 ) 2.1 Recommended Dosage The recommended dosage of ZEPZELCA as a single-agent and as a combination with atezolizumab or atezolizumab and hyaluronidase-tqjs is 3.2 mg/m 2 by intravenous infusion over 60 minutes every 21 days until disease progression or unacceptable toxicity [see Dosage and Administration (2.4) ]. Initiate treatment with ZEPZELCA only if absolute neutrophil count (ANC) is at least 1,500 cells/mm 3 and platelet count is at least 100,000/mm 3 .

• Myelosuppression : Monitor blood counts prior to each administration. Initiate treatment with ZEPZELCA only if baseline neutrophil count is ≥ 1,500 cells/mm 3 and platelet count is ≥ 100,000/mm 3 . For neutrophil count less than 500 cells/mm 3 or any value less than lower limit of normal, administer G-CSF. Withhold, reduce the dose, or permanently discontinue ZEPZELCA based on severity. ( 5.1 ) • Hepatotoxicity : Monitor liver function tests prior to initiating ZEPZELCA, periodically during treatment and as clinically indicated. Withhold, reduce the dose, or permanently discontinue ZEPZELCA based on severity. ( 5.2 ) • Extravasation Resulting in Tissue Necrosis : Consider use of a central venous catheter to reduce the risk of extravasation. Monitor patients for signs and symptoms of extravasation during the ZEPZELCA infusion. If extravasation occurs, immediately discontinue the infusion, remove the infusion catheter, and monitor for signs and symptoms of tissue necrosis. ( 5.3 ) • Rhabdomyolysis : Monitor creatine phosphokinase (CPK) prior to initiating ZEPZELCA and periodically during treatment as clinically indicated. Withhold, reduce the dose, or permanently discontinue ZEPZELCA based on severity. ( 5.4 ) • Embryo-Fetal Toxicity : Can cause fetal harm. Advise females and males of reproductive potential of the potential risk to a fetus and to use an effective method of contraception. ( 5.5 ) 5.1 Myelosuppression ZEPZELCA can cause severe and fatal myelosuppression including febrile neutropenia and sepsis, thrombocytopenia and anemia.

The following clinically significant adverse reactions are described elsewhere in the labeling: • Myelosuppression [see Warnings and Precautions (5.1) ] • Hepatotoxicity [see Warnings and Precautions (5.2) ] • Extravasation Resulting in Tissue Necrosis [see Warnings and Precautions (5.3) ] • Rhabdomyolysis [see Warnings and Precautions (5.4) ] The most common adverse reactions for ZEPZELCA as a single agent, including laboratory abnormalities, (≥ 20%) are leukopenia, lymphopenia, fatigue, anemia, neutropenia, increased creatinine, increased alanine aminotransferase, increased glucose, thrombocytopenia, nausea, decreased appetite, musculoskeletal pain, decreased albumin, constipation, dyspnea, decreased sodium, increased aspartate aminotransferase, vomiting, cough, decreased magnesium and diarrhea. ( 6.1 ) The most common adverse reactions, for ZEPZELCA in combination with atezolizumab including laboratory abnormalities, (≥ 30%) are: decreased lymphocytes, decreased platelets, decreased hemoglobin, decreased neutrophils, nausea, and fatigue/asthenia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Jazz Pharmaceuticals, Inc. at 1-800-520-5568 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.

• Lactation : Advise not to breastfeed. ( 8.2 ) • Hepatic Impairment : Avoid use of ZEPZELCA in patients with severe hepatic impairment. In patients with moderate hepatic impairment, reduce the dose of ZEPZELCA. ( 8.6 ) 8.1 Pregnancy Risk Summary Based on animal data and its mechanism of action [see Clinical Pharmacology (12.1) ] , ZEPZELCA can cause fetal harm when administered to a pregnant woman. There are no available data to inform the risk of ZEPZELCA use in pregnant women. Intravenous administration of a single lurbinectedin dose (approximately 0.2 times the 3.2 mg/m 2 clinical dose) to pregnant rats during the period of organogenesis caused embryolethality (see Data) . 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 to 4% and 15 to 20%, respectively. Data Animal Data In a reproductive toxicity study, administration of a single lurbinectedin dose of 0.6 mg/m 2 (approximately 0.2 times of the human dose of 3.2 mg/m 2 ) to pregnant rats on Gestation Day 10 resulted in 100% post-implantation loss.

Metabolism

Following the approved recommended dosage, geometric mean (%CV) of plasma C max and AUC 0-inf , were 107 µg/L (79%) and 551 µg•h/L (94%), respectively. No accumulation of lurbinectedin in plasma is observed upon administrations every 3 weeks.

• Jun 15, 2020NDANDA213702Jazz

1. 1Death13713%
2. 2Disease Progression1019.7%
3. 3Off Label Use747.1%
4. 4Neutropenia676.4%
5. 5Nausea656.2%
6. 6Thrombocytopenia565.4%
7. 7Fatigue464.4%
8. 8Febrile Neutropenia454.3%
9. 9Asthenia424.0%
10. 10Vomiting424.0%
11. 11Anaemia373.5%
12. 12Injection Site Reaction343.3%
13. 13Acute Kidney Injury282.7%
14. 14Diarrhoea272.6%
15. 15Pneumonia272.6%

The 10 most recently updated of 68 ClinicalTrials.gov registrations naming Lurbinectedin as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Clinical Study in Adult and Young Adult Patients With Advanced Desmoplastic Small Round Cell Tumor (DSRCT) ISG-TULIPS
  Recruiting · Phase 2 · Interventional · 20 enrolled · Italian Sarcoma Group
  NCT07328425updated 2026-06-11
• Lurbinectedin Plus Paclitaxel Versus Paclitaxel in Patients With Previously Treated Small Cell Lung Cancer
  Not yet recruiting · Phase 2 · Interventional · 69 enrolled · Yonsei University
  NCT07640932updated 2026-06-11
• A Study to Evaluate the Optimal Dose, Adverse Events and Change in Disease Activity of Intravenous ABBV-706 in Combination With Atezolizumab Versus Standard of Care as First-Line Treatment in Adult Participants With Previously Untreated Extensive Stage Small Cell Lung Cancer
  Recruiting · Phase 2 · Interventional · 180 enrolled · AbbVie
  NCT07155174updated 2026-06-09
• A Phase III, Open-Label Study of Maintenance Lurbinectedin in Combination With Atezolizumab Compared With Atezolizumab in Participants With Extensive-Stage Small-Cell Lung Cancer
  Active not recruiting · Phase 3 · Interventional · 660 enrolled · Hoffmann-La Roche
  NCT05091567updated 2026-06-09
• Maintenance Lurbinectedin in Combination With Serplulimab for Patients With ES-SCLC
  Recruiting · Phase 2 · Interventional · 30 enrolled · Guangzhou Institute of Respiratory Disease
  NCT06497530updated 2026-06-08
• Lurbinectedin With or Without Avelumab in Small Cell Carcinoma of the Bladder (LASER)
  Recruiting · Phase 2 · Interventional · 45 enrolled · National Cancer Institute (NCI)
  NCT06228066updated 2026-06-05
• Evaluate BL-M14D1 Plus Atezolizumab vs Standard of Care in First-Line Extensive-Stage Small Cell Lung Cancer
  Not yet recruiting · Phase 3 · Interventional · 550 enrolled · SystImmune Inc.
  NCT07625644updated 2026-06-04
• A Study of Ifinatamab Deruxtecan Versus Treatment of Physician's Choice in Subjects With Relapsed Small Cell Lung Cancer
  Recruiting · Phase 3 · Interventional · 540 enrolled · Daiichi Sankyo
  NCT06203210updated 2026-06-02
• A Study of Lurbinectedin in Combination With Durvalumab for the Treatment of Participants With ES-SCLC
  Not yet recruiting · Phase 2 · Interventional · 50 enrolled · Jazz Pharmaceuticals
  NCT07459634updated 2026-05-27
• Dose Attenuated Chemotherapy in Compromised Patients With Lung Cancer
  Recruiting · Phase 2 · Interventional · 280 enrolled · Fox Chase Cancer Center
  NCT05800587updated 2026-05-22

Frequently asked questions

How does Lurbinectedin work?

Lurbinectedin is an alkylating drug that binds guanine residues in the minor groove of DNA, forming adducts and resulting in a bending of the DNA helix towards the major groove. Adduct formation triggers a cascade of events that can affect the subsequent activity of DNA binding proteins, including some transcription factors, and DNA repair pathways, resulting in perturbation of the cell cycle and eventual cell death.

What is Lurbinectedin used for?

According to FDA labeling, Lurbinectedin carries indications including: ZEPZELCA is an alkylating drug indicated: • in combination with atezolizumab or atezolizumab and hyaluronidase-tqjs, for the maintenance treatment of adult patients with extensive-stage small cell lung cancer whose disease has not progressed after first-line induction therapy with atezolizumab or atezolizumab and hyaluronidase-tqjs, carboplatin and etoposide. ( 1.1 ) • For the treatment of adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Lurbinectedin?

Lurbinectedin is classified as Other antineoplastic agents, Alkylating Drug, Alkylating Activity, Cellular Cycle Alteration, Decreased DNA Integrity, Increased Cellular Death.

What are the brand names for Lurbinectedin?

Lurbinectedin is marketed under brand names including Zepzelca.

What are the contraindications for Lurbinectedin?

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