Developers at Jazz Pharmaceuticals plan to withdraw the approval status for lurbinectedin (Zepzelca) as a second-line treatment option for patients with small cell lung cancer (SCLC), according to a press release on financial results for the second quarter of 2026.1
Why is lurbinectedin being withdrawn?
The decision to withdraw lurbinectedin follows results from the phase 3 LAGOON trial (NCT05153239) assessing the agent vs investigator’s choice of topotecan or irinotecan among patients with relapsed second-line metastatic SCLC. In June 2026, investigators announced that lurbinectedin did not reach the trial’s primary end point of overall survival (OS).2
In the overall population, the median OS was 8.7 months with lurbinectedin monotherapy (n = 240) vs 11.1 months with lurbinectedin plus irinotecan (n = 189) and 10.7 months with control therapy (n = 242). Data revealed an HR of 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.
Investigators observed no new safety signals associated with lurbinectedin administered alone in combination with irinotecan. The rates of grade 3 or higher treatment-related adverse effects (TRAEs) were 35% with lurbinectedin monotherapy, 62.6% with lurbinectedin plus irinotecan, and 64.4% with topotecan or irinotecan.
In alignment with the FDA, developers plan to submit a labeling supplement to withdraw the second-line indication for lurbinectedin in the third quarter of 2026. This decision will not impact the indication for lurbinectedin as a first-line maintenance therapy option among patients with SCLC.
What is lurbinectedin’s regulatory history?
The FDA originally granted accelerated approval to lurbinectedin for adults with metastatic SCLC following disease progression on or after platinum-based chemotherapy in June 2020.3 Supporting data for the indication came from the phase 2 PM1183-B-005-14 trial (NCT02454972) evaluating the agent in 105 patients with metastatic disease.
Among the evaluable patients, the overall response rate (ORR) per RECIST v1.1 guidelines and investigator assessment was 35% (95% CI, 26%-45%), with a median duration of response (DOR) of 5.3 months (95% CI, 4.1-6.4). Based on independent review committee assessment, the ORR and median DOR were 30% (95% CI, 22%-40%) and 5.1 months (95% CI, 4.9-6.4), respectively.
Common AEs reported in the trial included laboratory abnormalities, were myelosuppression, fatigue, increased creatinine, increased alanine aminotransferase, increased glucose, nausea, decreased appetite, musculoskeletal pain, and decreased albumin.
Additionally, the FDA approved lurbinectedin plus atezolizumab (Tecentriq) or atezolizumab and hyaluronidase-tqjs (Tecentriq Hybrezaas) as a frontline maintenance regimen for patients with extensive-stage SCLC (ES-SCLC) who have not progressed on induction therapy in October 2025.4 Data from the phase 3 IMforte trial (NCT05091567) assessing lurbinectedin/atezolizumab vs atezolizumab alone supported the agency’s approval. Findings from IMforte were previously presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and subsequently published in The Lancet.5,6
Based on independent review facility (IRF) assessment, the median PFS was 5.4 months (95% CI, 4.2-5.8) with the lurbinectedin combination and 2.1 months (95% CI, 1.6-2.7) with atezolizumab alone (HR, 0.54; 95% CI, 0.43-0.67; P <.0001). Furthermore, the PFS rates in each arm were 41.2% vs 18.7% at 6 months and 20.5% vs 12.0% at 12 months. PFS outcomes per investigator assessment appeared to align with IRF evaluation (HR, 0.55; 95% CI, 0.45-0.68).
Data also showed a median OS of 13.2 months (95% CI, 11.9-16.4) vs 10.6 months (95% CI, 9.5-12.2) in the lurbinectedin/atezolizumab and atezolizumab monotherapy arms, respectively (HR, 0.73; 95% CI, 0.57-0.95; P = .0174). The 12-month OS rates were 56.3% vs 44.1% in each arm.
References
- Jazz Pharmaceuticals announces second quarter 2026 financial results. News release. Jazz Pharmaceuticals plc. August 3, 2026. Accessed August 5, 2026. https://tinyurl.com/47na5nnd
- 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 August 5, 2026. https://tinyurl.com/2dcu42hv
- FDA grants accelerated approval to lurbinectedin for metastatic small cell lung cancer. News release. FDA. June 15, 2020. Accessed August 5, 2026. https://tinyurl.com/h56z6vu3
- 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 August 5, 2026. https://tinyurl.com/35r3pers
- Paz-Ares L, Borghaei H, Liu SV, et al. Lurbinectedin (lurbi) + atezolizumab (atezo) as first-line (1L) maintenance treatment (tx) in patients (pts) with extensive-stage small cell lung cancer (ES-SCLC): primary results of the phase 3 IMforte trial. J Clin Oncol. 2025;43(suppl 16):8006. doi:10.1200/JCO.2025.43.16_suppl.8006
- 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. Published online June 2, 2025. doi:10.1016/S0140-6736(25)01011-6
