Lurbinectedin Second-Line SCLC Indication to Be Withdrawn After LAGOON

Jazz Pharmaceuticals plans to submit a labeling supplement to the FDA in the third quarter of 2026 requesting removal of the second-line metastatic small cell lung cancer (SCLC) indication for lurbinectedin (Zepzelca). The company disclosed the plan August 3, 2026, alongside its second-quarter 2026 financial results, stating that the decision follows results from the phase 3 LAGOON trial (NCT05153239) and reflects alignment with the FDA on next steps.¹ The first-line maintenance indication for lurbinectedin in combination with atezolizumab (Tecentriq) will not be affected.

LAGOON is the confirmatory trial required to verify the clinical benefit underlying lurbinectedin's original accelerated approval, which the FDA granted in June 2020 for adults with metastatic SCLC and disease progression on or after platinum-based chemotherapy.² That accelerated approval was based on objective response rate and duration of response data from the single-arm phase 2 Study B-005 trial (NCT02454972), which enrolled 105 patients and reported an overall response rate of 35% (95% CI, 26%-45%) and a median duration of response of 5.3 months (95% CI, 4.1-6.4).

Abou the LAGOON Trial

The randomized, open-label LAGOON trial enrolled 724 patients with relapsed SCLC across more than 200 sites in the US, Canada, and Europe whose disease had progressed after platinum-containing chemotherapy with or without an anti–PD-(L)1 agent.³ Patients were randomly assigned 1:1:1 to lurbinectedin monotherapy at 3.2 mg/m2 (n = 240), lurbinectedin at 2.0 mg/m2 plus irinotecan at 75 mg/m2 (n = 242), or investigator's choice of topotecan or irinotecan (n = 242). The trial did not meet its primary end point of overall survival (OS) for either lurbinectedin arm vs control.

Across the overall population, median OS was 8.7 months with lurbinectedin monotherapy, 10.9 months with the lurbinectedin-irinotecan combination, and 10.7 months with control therapy The HR for monotherapy vs control was 1.190 (95% CI, 0.959-1.476); the HR for the combination vs control was 0.902 (95% CI, 0.729-1.115). Patients with central nervous system (CNS) metastases who received lurbinectedin monotherapy fared worse, with a median OS of 7.1 months and an HR of 1.791 (95% CI, 1.162-2.760) vs control; among patients without CNS metastases, median OS was 9.6 months with monotherapy and 11.1 months with the combination.

No new safety signals emerged. Treatment-related adverse events (TRAEs) of any grade occurred in 78.5% of patients on lurbinectedin monotherapy compared with 95.0% on the combination regimen and 93.8% on control therapy; grade 3 or higher TRAEs were reported in 35.0%, 62.6%, and 64.4% of patients, respectively.

First-Line Maintenance Indication Remains Unaffected

The first-line maintenance indication, unaffected by the planned label change, rests on the phase 3 IMforte trial (NCT05091567).⁴ In IMforte, adults with extensive-stage SCLC whose disease had not progressed after induction therapy with atezolizumab plus carboplatin and etoposide were randomized to maintenance lurbinectedin plus atezolizumab (n = 242) or atezolizumab alone (n = 241). The combination improved progression-free survival by independent review facility (5.4 months vs 2.1 months; stratified HR, 0.54; 95% CI, 0.43-0.67; P <.0001) and OS (HR, 0.73; 95% CI, 0.57-0.95; P =.0174) vs atezolizumab alone. The FDA approved lurbinectedin plus atezolizumab for first-line maintenance therapy in extensive-stage SCLC in October 2025.⁵

"[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,” said Rob Iannone, MD, MSCE, executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals, in a news release.³

REFERENCES

1. Jazz Pharmaceuticals Announces Second Quarter 2026 Financial Results. News release. Jazz Pharmaceuticals. August 3, 2026. Accessed August 5, 2026. https://tinyurl.com/r7ux7t3x

2. FDA grants accelerated approval to lurbinectedin for metastatic small cell lung cancer. News release. US FDA. Update June 16, 2020. Accessed August 5, 2026. https://tinyurl.com/5h5rpn92

3. 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 August 5, 2026. https://tinyurl.com/43kzc4pu

4. Paz-Ares L, Borghaei H, Liu SV, et al. Efficacy and safety of first-line maintenance therapy with lurbinectedin plus atezolizumab in extensive-stage small-cell lung cancer (IMforte): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2025 Jun 14;405(10495):2129-2143. doi: 10.1016/S0140-6736(25)01011-6.

5. FDA approves lurbinectedin in combination with atezolizumab or atezolizumab and hyaluronidase-tqjs for extensive-stage small cell lung cancer. News release. US FDA. October 2, 2025. Accessed August 5, 2026. https://tinyurl.com/45j99bym