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Bending the Curve Trial by Trial
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Other cytotoxics, enzymes and natural productsIn useDerivative of an earlier drug

Lurbinectedin

Also known as Zepzelca, PM01183

A synthetic derivative of trabectedin that binds DNA. In the US it was approved in 2025 with atezolizumab as maintenance for extensive-stage small cell lung cancer; the 2020 second-line indication was voluntarily withdrawn in 2026.

From discovery to approval

  1. 2010 · Earliest report found

    Leal and colleagues (2010) described PM01183, now lurbinectedin, as a new synthetic tetrahydroisoquinoline alkaloid in phase I development that binds DNA. Reviews call it a synthetic derivative of trabectedin; a tetrahydro-beta-carboline replaces the tetrahydroisoquinoline in the C subunit.[2][3][4]

  2. 2020-06-15 · FDA accelerated

    Adult patients with metastatic small cell lung cancer with disease progression on or after prior platinum-based chemotherapy; approved under accelerated approval based on overall response rate and duration of response (NDA 213702).[5]

  3. 2025-10-02 · FDA regular

    In combination with atezolizumab or atezolizumab and hyaluronidase-tqjs, 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 (NDA 213702/S-011; no accelerated-approval wording for this indication, so 'regular' is an inference).[6]

  4. 2026-05-29 · EMA regular

    Marketing authorisation issued 29 May 2026 (EPAR page); with atezolizumab, maintenance treatment of adults with extensive-stage small cell lung cancer whose disease has not progressed after first-line induction with atezolizumab, carboplatin and etoposide. The page does not mention conditional or exceptional-circumstances authorisation, so 'regular' is an inference.[7]

  5. 2026-09-30 · FDA withdrawn

    Voluntary withdrawal, at the sponsor's request, of the 2020 accelerated-approval indication (metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy): FDA's supplement approval letter of 30 September 2026 (NDA 213702/S-013) releases postmarketing requirement 3831-7 because of the voluntary withdrawal. FDA's withdrawn-approvals page lists the same date (9/30/2026). Neither document gives a reason.[8]

How it works

The 2020 FDA label calls it an alkylating drug that binds guanine in the minor groove of DNA, forming adducts and bending the helix. This affects DNA-binding proteins and DNA repair pathways, disturbing the cell cycle and leading to cell death.[1]

Where it came from and why

No source read says why it was made. The 2010 report found that it bound DNA and caused double-strand breaks, S-phase accumulation and apoptosis, with a mean GI50 of 2.7 nM in 23 cell lines, and inhibited tumour growth in four mouse xenograft models.

Cancers

  • Small cell lung cancer, second line

    The 2020 accelerated approval covered metastatic small cell lung cancer with progression on or after platinum-based chemotherapy; the single-arm phase 2 basket trial enrolled 105 patients.[9]

  • Small cell lung cancer, maintenance

    The EU authorisation of 29 May 2026 covers maintenance, with atezolizumab, in adults with extensive-stage disease that has not progressed after first-line induction with atezolizumab, carboplatin and etoposide.[7]

Family and partners

Derived from: Trabectedin

Worth knowing

  • In the single-arm phase 2 basket trial in second-line small cell lung cancer, investigator-assessed overall response was seen in 37 of 105 patients (35.2%, 95% CI 26.2 to 45.2).[9]
  • The first-in-human phase I study treated 31 patients with advanced solid tumours; doses rose from 0.02 to 5.0 mg/m2 and a flat 7.0 mg one-hour infusion every three weeks was recommended.[10]
  • An FDA letter signed 30 September 2026 approved the sponsor's request to withdraw voluntarily the 2020 accelerated-approval indication; it states that resuming marketing for that indication would need approval of an efficacy supplement.[8]

On this site

References

  1. U.S. Food and Drug Administration. Zepzelca (lurbinectedin) prescribing information, NDA 213702, original approval June 2020 (the label states it may not be the latest approved). Source
  2. Leal JF, Martínez-Díez M, García-Hernández V, Moneo V, Domingo A, Bueren-Calabuig JA, et al. PM01183, a new DNA minor groove covalent binder with potent in vitro and in vivo anti-tumour activity. Br J Pharmacol. 2010;161(5):1099-110. PubMedDOI
  3. Manzo A, Sforza V, Carillio G, Palumbo G, Montanino A, Sandomenico C, et al. Lurbinectedin in small cell lung cancer. Front Oncol. 2022;12:932105. PubMedDOI
  4. Povo-Retana A, Landauro-Vera R, Alvarez-Lucena C, Cascante M, Boscá L. Trabectedin and Lurbinectedin Modulate the Interplay between Cells in the Tumour Microenvironment-Progresses in Their Use in Combined Cancer Therapy. Molecules. 2024;29(2). PubMedDOI
  5. FDA. Accelerated approval letter, NDA 213702 (Zepzelca, lurbinectedin; metastatic small cell lung cancer with disease progression on or after prior platinum-based chemotherapy), electronic signature 15 June 2020. Source
  6. FDA. Supplement approval and fulfillment of postmarketing requirement letter, NDA 213702/S-011 (Zepzelca, lurbinectedin; with atezolizumab, maintenance treatment of extensive-stage small cell lung cancer), electronic signature 2 October 2025. Source
  7. EMA. Zepzelca (lurbinectedin): European public assessment report page; marketing authorisation issued 29/05/2026 (page read 20 October 2026). Source
  8. FDA. Supplement approval / release from postmarketing requirement letter, NDA 213702/S-013 (Zepzelca, lurbinectedin; voluntary withdrawal of the accelerated-approval indication for metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy), electronic signature 30 September 2026. Source
  9. Trigo J, Subbiah V, Besse B, Moreno V, López R, Sala MA, et al. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. Lancet Oncol. 2020;21(5):645-654. PubMedDOI
  10. Elez ME, Tabernero J, Geary D, Macarulla T, Kang SP, Kahatt C, et al. First-in-human phase I study of Lurbinectedin (PM01183) in patients with advanced solid tumors. Clin Cancer Res. 2014;20(8):2205-14. PubMedDOI
  11. Markham A. Lurbinectedin: First Approval. Drugs. 2020;80(13):1345-1353. PubMedDOI