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| Pronunciation | /ˌlɜːrbɪˈnɛktɪdɪn/ LUR-bi-NEK-ti-din |
| Trade names | Zepzelca |
| Other names | PM-01183 |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a620049 |
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| Routes of administration | Intravenous |
| Drug class | Antineoplastic agent |
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| Formula | C41H44N4O10S |
| Molar mass | 784.88 g·mol−1 |
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Lurbinectedin, sold under the brand nameZepzelca, is amedication used for the treatment ofsmall cell lung cancer.[5][6][7]
Lurbinectedin is a synthetic tetrahydropyrrolo [4,3,2-de]quinolin-8(1H)-one alkaloid analogue with potential antineoplastic activity.[8] Lurbinectedin covalently binds to residues lying in the minor groove of DNA, which may result in delayed progression through S phase, cell cycle arrest in the G2/M phase and cell death.[8]
The most common side effects include 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.[5][6][7]
Lurbinectedin was approved for medical use in the United States in June 2020.[9][5][6][7][10]
Lurbinectedin isindicated for the treatment of adults with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy.[7]
In October 2025, the indication for lurbinectedin was expanded to include using lurbinectedin in combination withatezolizumab or in combination withatezolizumab/hyaluronidase for the maintenance treatment of adults with extensive-stage small cell lung cancer whose disease has not progressed after first-line induction therapy with atezolizumab or atezolizumab and hyaluronidase,carboplatin, andetoposide.[11]
The USprescribing information for lurbinectedin includes warnings and precautions for myelosuppression, hepatotoxicity, extravasation resulting in tissue necrosis, rhabdomyolysis, and embryo-fetal toxicity.[11] The prescribing information foratezolizumab and foratezolizumab/hyaluronidase include warnings and precautions for severe and fatal immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.[11]
Lurbinectedin is structurally similar totrabectedin, although the tetrahydroisoquinoline present in trabectedin is replaced with a tetrahydro β-carboline which enables lurbinectedin to exhibit increased antitumor activity compared with trabectedin.[12]
Synthesis of lurbinectedin starts from small, common starting materials that require twenty-six individual steps to produce the drug with overall yield of 1.6%.[13]
According to PharmaMar,[14][unreliable medical source?] lurbinectedin inhibits the activetranscription of the encoding genes. This has two consequences. It promotestumor cell death and normalizes the tumor microenvironment. Active transcription is the process by which there are specific signal where information contained in theDNA sequence is transferred to anRNA molecule. This activity depends on the activity of an enzyme calledRNA polymerase II. Lurbinectedin inhibits transcription through a very precise mechanism. Firstly, lurbinectedin binds to specific DNA sequences. It is at these precise spots that RNA polymerase II slides down the DNA to produce RNA that is blocked and degraded by lurbinectedin. Lurbinectedin also has important role in tumor microenvironment. The tumor cells act uponmacrophages to avoid them from behaving like an activator of theimmune system. Macrophages can contribute to tumor growth and progression by promoting tumor cell proliferation and invasion, fostering tumor angiogenesis and suppressing antitumor immune cells.[15][16]
Lurbinectedin was approved for medical use in the United States in June 2020.[9][5][6][7][10]
Efficacy was demonstrated in the PM1183-B-005-14 trial (Study B-005; NCT02454972), a multi-center open-label, multi-cohort study enrolling 105 participants with metastatic small cell lung cancer who had disease progression on or after platinum-based chemotherapy.[7][10] Participants received lurbinectedin 3.2 mg/m2 by intravenous infusion every 21 days until disease progression or unacceptable toxicity.[7] The trial was conducted at 26 sites in the United States, Great Britain, Belgium, France, Italy, Spain and Czech Republic.[10]
The USFood and Drug Administration (FDA) granted the application for lurbinectedin priority review andorphan drug designations and granted the approval of Zepzelca to Pharma Mar S.A.[7][17]
The efficacy of lurbinectedin used in combination withatezolizumab or in combination withatezolizumab/hyaluronidase was evaluated in IMforte (NCT05091567), a randomized, multi-center, open-label trial in participants receiving first-line treatment for extensive-stage small cell lung cancer.[11] In IMforte, 483 participants with extensive-stage small cell lung cancer whose disease had not progressed after completion of four cycles of atezolizumab,carboplatin, andetoposide (induction treatment) were randomized (1:1) to receive either lurbinectedin in combination with atezolizumab administered intravenously or atezolizumab intravenously alone until disease progression or unacceptable toxicity.[11]
In October 2025, the FDA approved a combination ofatezolizumab,hyaluronidase, and lurbinectedin for the treatment of adults with extensive-stagesmall cell lung cancer.[11][18]
Lurbinectedin can be used as monotherapy in the treatment of small cell lung cancer.[medical citation needed] Lurbinectedin monotherapy demonstrated the following clinical results in relapsed extensive stage small cell lung cancer:
Lurbinectedin is also being investigated in combination withdoxorubicin as second-line therapy in a randomized Phase III trial.[medical citation needed] While overall survival in this trial is not yet known, response rates at second line were
Lurbinectedin is available in the US under Expanded Access Program (EAP).[20][22]
This article incorporates text from this source, which is in thepublic domain. This article incorporates text from this source, which is in thepublic domain. This article incorporates text from this source, which is in thepublic domain. This article incorporates text from this source, which is in thepublic domain.
