Jazz Pharmaceuticals has announced top-line results from the phase 3 Lagoon trial, conducted by PharmaMar, evaluating Zepzelca (lurbinectedin) in patients with relapsed (second-line) metastatic small cell lung cancer (SCLC). The trial did not meet its primary endpoint of overall survival (OS) evaluating Zepzelca as monotherapy or in combination with irinotecan compared to investigators’ choice of topotecan or irinotecan. No new safety signals were identified with Zepzelca monotherapy or in combination with irinotecan, and the overall safety profiles of the investigational arms were consistent with the known safety profile of each agent.
The full US approval of Zepzelca in 2025 is based on the phase 3 IMforte trial, which evaluated Zepzelca in combination with atezolizumab as first-line maintenance treatment for patients with extensive-stage SCLC.
In the trial, the Zepzelca and atezolizumab combination demonstrated a statistically significant improvement in the primary endpoints of OS and progression-free survival (PFS), as assessed by an independent review facility, compared to treatment with atezolizumab alone.
The Zepzelca and atezolizumab combination reduced the risk of disease progression or death by 46% and the risk of death by 27%, compared to atezolizumab maintenance therapy alone. The results are distinct from the IMforte trial and do not impact Zepzelca approval in the first-line maintenance setting.
The company has shared the results with the FDA and will discuss next steps with the agency regarding its post-marketing requirements for the Zepzelca second-line indication.
The study results do not impact the company’s 2026 guidance.
Key results from the phase 3 trial
The trial included a broader patient population than the phase 2 pivotal trial that supported the second-line accelerated approval, including patients with a history of CNS involvement. Efficacy of Zepzelca in the subset of patients without a history of CNS involvement was more comparable to the control arm, which performed better than historical precedent.
| Trial Population | Zepzelca monotherapy Median OS | Zepzelca + irinotecan Median OS | Control Median OS | HR (95% CI) Zepzelca vs Control | HR (95% CI) Zepzelca+irinotecan vs Control |
| Overall | 8.7 (n=240) | 10.9 (n=242) | 10.7 (n=242) | 1.190 (0.959, 1.476) | 0.902 (0.729, 1.115) |
| Without CNS metastases | 9.6 (n=182) | 11.1 (n=189) | 10.7 (n=186) | 1.106 (0.875, 1.398) | 0.922 (0.729, 1.166) |
| With CNS metastases | 7.1 (n=58) | 10.5 (n= 53) | 10.3 (n=56) | 1.791 (1.162, 2.760) | 1.107 (0.724, 1.692) |
The overall safety profile for Zepzelca was favourable relative to the control arm. Treatment-related adverse events (TRAE) were 78.5% with Zepzelca, 95% with Zepzelca + irinotecan, and 93.8% with the control arm. TRAEs Grade ≥ 3 were 35% with Zepzelca, 62.6% with Zepzelca + irinotecan, and 64.4% with the control arm.
