Jazz Pharmaceuticals has announced that Zepzelca (lurbinectedin) failed to meet its primary endpoint of overall survival in the Phase III Lagoon trial, threatening the drug's accelerated FDA approval for second-line metastatic small cell lung cancer (SCLC).
The Lagoon study, conducted by PharmaMar (which licenses US rights to Jazz), evaluated Zepzelca as monotherapy and in combination with irinotecan against the investigator's choice of chemotherapy (topotecan or irinotecan) in patients with previously treated metastatic SCLC.
Zepzelca monotherapy performed worse than the control arm, with patients living a median of 8.7 months compared with 10.7 months in the control group — a 19% higher risk of death.
The Zepzelca-irinotecan combination showed a marginal 9.8% improvement in overall survival that did not reach statistical significance.
Jazz said it has notified the FDA of the results and will discuss next steps regarding the drug's second-line post-marketing requirements.
The outcome marks the second Phase III failure in this indication; the earlier Atlantis trial also failed to meet its overall survival endpoint, though the FDA permitted Zepzelca to remain on the market at the time, citing an unmet medical need and noting that Atlantis used a lower dose than the approved formulation.
The Lagoon miss does not, however, affect Zepzelca's separate full approval, granted in 2025, for use in combination with Roche's atezolizumab (Tecentriq) as a first-line maintenance treatment for extensive-stage SCLC.
That indication, supported by a 27% reduction in mortality risk in the Phase III IMforte trial, is now the primary commercial driver for the drug.
Q1 2026 Zepzelca revenues reached $101m — a 60% year-on-year increase — with first-line maintenance uptake partially offsetting a decline in second-line use that Jazz has indicated is expected to continue.
Jazz added that the Lagoon results will not affect its 2026 financial outlook.