Lurbinectedin Misses Survival End Point in Second-Line SCLC Trial

Lurbinectedin (Zepzelca) with or without irinotecan did not meet the primary end point of overall survival (OS) compared with investigator’s choice of topotecan or irinotecan among patients with relapsed second-line metastatic small cell lung cancer (SCLC), according to a press release on findings from the phase 3 LAGOON trial (NCT05153239).¹

Across the overall population, the median OS was 8.7 months with lurbinectedin monotherapy (n = 240), 10.9 months with lurbinectedin/irinotecan (n = 242), and 10.7 months with control therapy (n = 242). The HR was 1.190 (95% CI, 0.959-1.476) for lurbinectedin monotherapy vs control and 0.902 (95% CI, 0.729-1.115) for the combination vs control.

Among those without central nervous system (CNS) metastases, the median OS was 9.6 months with lurbinectedin monotherapy (n = 182), 11.1 months with lurbinectedin/irinotecan (n = 189), and 10.7 months with control therapy (n = 186). The HR was 1.106 (95% CI, 0.875-1.398) for lurbinectedin alone vs control and 0.922 (95% CI, 0.729-1.166) for the combination vs control.

Regarding patients with CNS metastases, the median OS was 7.1 months with lurbinectedin alone (n = 58), 10.5 months with lurbinectedin/irinotecan (n = 53), and 10.3 months with control therapy (n = 56). The HR was 1.791 (95% CI, 1.162-2.760) for lurbinectedin monotherapy compared with control and 1.107 (95% CI, 0.724-1.692) for the combination vs control.

Investigators observed no new safety signals with lurbinectedin alone or in combination with irinotecan, and the overall safety profile of the combination regimen was comparable with prior reports of each individual agent. The rates of treatment-related adverse effects (TRAEs) were 78.5% with lurbinectedin alone, 95% with the combination regimen, and 93.8% with investigator’s choice of topotecan or irinotecan. Additionally, grade 3 or higher TRAEs occurred in 35%, 62.6%, and 64.4% of patients in each respective arm.

Developers have shared findings from the LAGOON trial with the FDA and will discuss next steps regarding post-marketing requirements for lurbinectedin as a second-line therapeutic option.

“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 at Jazz Pharmaceuticals, stated in the press release.¹ “[Lurbinectedin] is an important treatment in SCLC and, based on the strength of the 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.”

The FDA previously approved lurbinectedin plus atezolizumab (Tecentriq) as maintenance therapy in the frontline setting among those with extensive-stage SCLC who have not progressed on induction therapy in October 2025.² The agency based its decision on data from the phase 3 IMforte trial.

In the multicenter phase 3 LAGOON trial, 724 patients were randomly assigned 1:1:1 to receive lurbinectedin at 3.2 mg/m² alone, lurbinectedin at 2.0 mg/m² plus irinotecan at 75 mg/m², or investigator’s choice of topotecan or irinotecan.

The trial’s primary end point was OS. Secondary end points included progression-free survival per independent review committee (IRC) assessment, overall response rate per IRC evaluation, duration of response, and patient-reported outcomes.³ Patients 18 years and older with histologically or cytologically confirmed SCLC and 1 prior line of platinum-containing chemotherapy with or without anti–PD-(L)1 agents were eligible for enrollment on the trial.

References

1. Jazz Pharmaceuticals provides update on Zepzelca® (lurbinectedin) phase 3 LAGOON trial in second-line small cell lung cancer. News release. Jazz Pharmaceuticals plc. June 12, 2026. Accessed June 12, 2026. https://tinyurl.com/2dcu42hv
2. FDA approves lurbinectedin in combination with atezolizumab or atezolizumab and hyaluronidase-tqjs for extensive-stage small cell lung cancer. News release. FDA. October 2, 2025. Accessed June 12, 2026. https://tinyurl.com/35r3pers
3. Clinical trial of lurbinectedin as single-agent or in combination with irinotecan versus topotecan or irinotecan in patients with relapsed small-cell lung cancer (LAGOON). ClinicalTrials.gov. Updated May 13, 2026. Accessed June 12, 2026. https://tinyurl.com/ykzs726s