Lurbinectedin (Zepzelca) failed to produce a statistically significant improvement in overall survival (OS) as monotherapy or in combination with irinotecan vs investigator’s choice of topotecan or irinotecan in patients with relapsed, metastatic small cell lung cancer (SCLC), missing the primary end point of the phase 3 LAGOON trial (NCT05153239).1
The median OS was 8.7 months with lurbinectedin alone, 10.9 months with lurbinectedin plus irinotecan, and 10.7 months with investigator’s choice, with HRs of 1.190 (95% CI, 0.959-1.476) and 0.902 (95% CI, 0.729-1.115) for lurbinectedin alone and in combination vs the control, respectively.
No new safety signals were identified with lurbinectedin alone or in combination with irinotecan, and the overall safety profiles seen within both investigational arms were consistent with the known safety profiles of each agent therein.
Results of the trial have been shared with the US regulatory agency to determine what post marketing may be required for lurbinectedin’s second-line indication.1,2
“Relapsed SCLC is an aggressive cancer with a poor prognosis and patients continue to need treatment options, including in later lines of therapy. We thank the investigators, trial sites and patients who were involved in the LAGOON trial, along with our partner, PharmaMar,” Rob Iannone, MD, MSCE, executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals, stated in a news release.1 “[Lurbinectedin] is an important treatment in SCLC and, based on the strength of the [phase 3] IMforte trial [NCT05091567] results, we believe its most beneficial use is in the first-line maintenance setting in combination with immunotherapy given the rapid progression of metastatic SCLC after first-line chemotherapy induction.”
Lurbinectedin Misses the Mark in Relapsed SCLC
- In the phase 3 LAGOON trial, lurbinectedin monotherapy and lurbinectedin plus irinotecan both failed to demonstrate a statistically significant OS benefit vs investigator’s choice of topotecan or irinotecan, with median OS values of 8.7 months, 10.9 months, and 10.7 months, respectively.
- Notably, patients with CNS metastases fared worse on lurbinectedin monotherapy, with a median OS of 7.1 months and a HR of 1.791 (95% CI, 1.162-2.760) vs the control arm.
- Jazz Pharmaceuticals is now evaluating post-marketing requirements with the FDA for lurbinectedin’s second-line indication.
How was the trial designed to confirm the earlier efficacy seen in the phase 2 setting?
Accelerated approval of the agent was based on data from the single-arm, phase 2 PM1183-B-005-14 trial (Study B-005; NCT02454972) of 105 patients with SCLC who had progressed on platinum-based therapy. In this population lurbinectedin monotherapy produced an overall response rate was 35% (95% CI, 26%-45%) and median duration of response of 5.3 months (95% CI, 4.1-6.4).2
The randomized, multicenter, open-label LAGOON trial enrolled patients with SCLC, whose disease had progressed after prior platinum-containing chemotherapy with or without anti–PD-(L)1 agents.1 Patients were randomly assigned 1:1:1 to one of three arms: lurbinectedin at 3.2 mg/m2 as monotherapy (n = 240), which is the approved dose in the US, lurbinectedin at 2.0 mg/m2 in combination with irinotecan at 75 mg/m2 (n = 242), or investigator’s choice of topotecan or irinotecan (n = 242). The trial enrolled 724 patients from over 200 sites globally, including in the US, Canada, and Europe.
What other efficacy signals were shared in the topline release?
Efficacy was also evaluated in patients with and without central nervous system (CNS) metastases. In patients without CNS metastases the median OS was 9.6 months with lurbinectedin alone (n = 182), 11.1 months with lurbinectedin plus irinotecan (n = 189), and 10.7 months with investigator’s choice (n = 186), with HRs of 1.106 (95% CI, 0.875-1.398) and 0.922 (95% CI, 0.729-1.116) for lurbinectedin alone and in combination vs the control, respectively.
In patients with CNS metastases, the median OS was 7.1 months with lurbinectedin alone (n = 58), 10.5 months with lurbinectedin plus irinotecan (n = 53), and 10.3 months with investigator’s choice (n = 56), with HRs of 1.791 (95% CI, 1.162-2.760) and 1.107 (95% CI, 0.724-1.692) for lurbinectedin alone and in combination vs the control, respectively.
Was additive toxicity seen with lurbinectedin plus chemotherapy?
With respect to safety, treatment-related adverse effects (TRAEs) occurred in 78.5% of patients who received lurbinectedin alone, 95% with lurbinectedin plus irinotecan, and 93.8% with investigator’s choice. Grade 3 or greater TRAEs occurred in 35% of patients who received lurbinectedin, 62.6% with lurbinectedin plus irinotecan, and 64.4% with investigator’s choice.
References
- Jazz Pharmaceuticals provides update on Zepzelca (lurbinectedin) phase 3 LAGOON trial in second-line small cell lung cancer. News release. Jazz Pharmaceuticals. June 12, 2026. Accessed June 12, 2026. https://investor.jazzpharma.com/news-releases/news-release-details/jazz-pharmaceuticals-provides-update-zepzelcar-lurbinectedin
- FDA grants accelerated approval to lurbinectedin for metastatic small cell lung cancer. FDA. Updated June 16, 2020. Accessed June 12, 2026. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-lurbinectedin-metastatic-small-cell-lung-cancer
