Jazz Pharmaceuticals reported that the Phase 3 LAGOON trial of Zepzelca (lurbinectedin) in relapsed small cell lung cancer failed to improve overall survival versus investigator-selected chemotherapy, while maintaining a consistent safety profile.
Written By: Meghana Jinka, PharmD
Reviewed By: Pharmacally Editorial Team
Jazz Pharmaceuticals announced that the Phase 3 LAGOON trial (NCT05153239) evaluating Zepzelca® (lurbinectedin) in relapsed small cell lung cancer (SCLC) did not meet its primary endpoint of overall survival (OS). Neither lurbinectedin monotherapy nor the lurbinectedin-irinotecan combination achieved a statistically significant OS improvement compared with investigator-selected chemotherapy.
The study enrolled 724 patients across more than 200 sites in the United States, Canada, and Europe. Participants had progressed following platinum-based chemotherapy, with or without prior PD-1/PD-L1 therapy, and were randomized to lurbinectedin monotherapy, lurbinectedin plus irinotecan, or investigator’s choice of topotecan or irinotecan. Unlike the Phase 2 study that supported accelerated approval, LAGOON included patients with central nervous system (CNS) involvement.
LAGOON was the confirmatory Phase 3 study required under Zepzelca’s accelerated approval in relapsed SCLC, making the results an important milestone in evaluating the drug’s long-term clinical benefit in this setting.
Efficacy Results
Median OS was 8.7 months with lurbinectedin monotherapy, 10.9 months with the combination, and 10.7 months with control therapy. Hazard ratios were 1.190 (95% CI: 0.959–1.476) for monotherapy versus control and 0.902 (95% CI: 0.729–1.115) for the combination versus control.
Subgroup analyses highlighted differences by CNS status. Among patients without CNS metastases, OS outcomes were broadly similar across arms (9.6, 11.1, and 10.7 months, respectively). In patients with CNS metastases, lurbinectedin monotherapy was associated with inferior survival compared with control (7.1 vs. 10.3 months; HR 1.791, 95% CI: 1.162–2.760). Jazz reported that investigator-selected chemotherapy performed better than expected relative to historical benchmarks, narrowing 0the margin between treatment groups.
Safety Findings
Safety results were consistent with known agent profiles. Treatment-related adverse events occurred in 78.5% of patients on lurbinectedin monotherapy, 95.0% on the combination, and 93.8% in the control arm. Grade 3 or higher treatment-related adverse events were reported in 35.0%, 62.6%, and 64.4% of patients, respectively. No new safety signals were identified.
Rob Iannone, M.D., M.S.C.E., Executive Vice President, Global Head of Research and Development and Chief Medical Officer at Jazz Pharmaceuticals, thanked patients, investigators, trial sites, and partner PharmaMar for their participation and emphasized the continued need for new treatment options for patients with relapsed SCLC.
Regulatory Context
LAGOON was conducted as the confirmatory study supporting Zepzelca’s accelerated approval in previously treated SCLC. Jazz has submitted the findings to the FDA as part of its post-marketing commitment. While the trial did not confirm an overall survival benefit in the relapsed setting, the company said the results do not affect Zepzelca’s fully approved first-line maintenance indication.
That approval, granted in 2025, was based on the Phase 3 IMforte trial, in which lurbinectedin plus atezolizumab significantly improved overall survival and progression-free survival compared with atezolizumab alone, reducing the risk of disease progression or death by 46% and the risk of death by 27%.
Jazz noted that evidence from the IMforte study suggests lurbinectedin may provide greater benefit earlier in the treatment pathway, particularly when combined with immunotherapy.
Reference
About the Writer
Meghana Jinka (LinkedIn) is a Pharm.D graduate with a strong interest in clinical pharmacy, clinical research, pharmacovigilance, and medical writing. She has developed expertise in evaluating scientific literature, interpreting clinical data, and communicating complex medical information in a clear and accessible manner. Through clinical training, patient counseling, and healthcare awareness activities, she has gained practical experience in evidence-based medicine and patient-centered care. Passionate about healthcare communication, Meghana is committed to developing accurate, engaging, and evidence-based healthcare documents that support healthcare professionals and the wider community.