Lurbinectedin Maintenance Combo Earns FDA Priority Review in ES-SCLC

Supporting data for the sNDA came from the phase 3 IMforte trial (NCT05091567) assessing maintenance therapy with lurbinectedin plus atezolizumab vs atezolizumab alone in patients with ES-SCLC.

The FDA has granted priority review to a supplemental new drug application (sNDA) for lurbinectedin (Zepzelca) plus atezolizumab (Tecentriq) as maintenance therapy in the frontline setting for patients with extensive-stage small cell lung cancer (ES-SCLC) without progression on induction therapy with atezolizumab plus carboplatin/etoposide, according to a press release from the developer, Jazz Pharmaceuticals.¹

The regulatory agency has set a Prescription Drug User Fee Act date of October 7, 2025, for its decision on approving the lurbinectedin-based regimen for this ES-SCLC population.

Supporting data for the sNDA came from the phase 3 IMforte trial (NCT05091567) assessing maintenance therapy with lurbinectedin plus atezolizumab vs atezolizumab alone in patients with ES-SCLC. Investigators presented findings from the IMforte trial at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and subsequently published them in The Lancet.^2,3

From the time of randomization to the maintenance phase, the median progression-free survival (PFS) was 5.4 months (95% CI, 4.2-5.8) with the lurbinectedin combination vs 2.1 months (95% CI, 1.6-2.7) with atezolizumab alone (HR, 0.54; 95% CI, 0.43-0.67; P <.0001). The PFS rates in each respective arm were 41.2% vs 18.7% at 6 months and 20.5% vs 12.0% at 12 months.

Additional data showed a median overall survival (OS) of 13.2 months (95% CI, 11.9-16.4) in the lurbinectedin combination arm and 10.6 months (95% CI, 9.5-12.2) in the atezolizumab monotherapy arm (HR, 0.73; 95% CI, 0.57-0.95; P = .017). At 12 months, the OS rates were 56.3% vs 44.1% in each arm; the lurbinectedin combination achieved an absolute risk reduction of 12.1% (95% CI, 1.97%-22.31%) for OS.

The addition of lurbinectedin to atezolizumab improved PFS and OS across most predefined subgroups including sex, race, and ethnicity, although no OS improvement occurred among patients with lactate dehydrogenase concentrations exceeding the upper limit of normal and those with prophylactic cranial irradiation.

Data from IMforte showed no new or unexpected safety signals associated with the lurbinectedin combination. The most common grade 3/4 adverse effects across the experimental arm included anemia (8%), decreased neutrophil counts (7%), decreased platelet counts (7%), and neutropenia (5%).

“IMforte is the first phase 3 study to show PFS and OS improvement with first-line maintenance treatment for ES-SCLC, highlighting the potential of lurbinectedin plus atezolizumab to become a new standard of care for first-line maintenance therapy in patients with this aggressive and difficult-to-treat disease,” lead study author Luis Paz-Ares, MD, PhD, of Hospital Universitario 12 de Octubre, H12O-CNIO Lung Cancer Unit, Universidad Complutense and Ciberonc, in Madrid, Spain, stated in a press briefing ahead of the 2025 ASCO Annual Meeting.²

In the open-label, multi-center IMforte trial, 483 patients who entered the maintenance phase were randomly assigned 1:1 to receive lurbinectedin plus atezolizumab (n = 242) or atezolizumab alone (n = 241). Investigators administered lurbinectedin at 3.2 mg/m² with granulocyte colony-stimulating factor prophylaxis plus atezolizumab at 1200 mg every 3 weeks or atezolizumab alone every 3 weeks.

The trial’s primary end points were independent review facility (IRF)–evaluated PFS per RECIST v1.1 criteria and OS. Secondary end points included investigator-assessed PFS, objective response rate, and duration of response.

“The FDA's Priority Review designation for [lurbinectedin] in combination with atezolizumab as a first-line maintenance treatment highlights the urgent need for new approaches and the potential benefit of [lurbinectedin] for patients with [ES-SCLC], a disease with limited therapeutic options and high unmet need. We are pleased to have received this review designation after presenting the IMforte trial data at ASCO 2025 with simultaneous publication in The Lancet,” 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 “Together, these milestones bring us a step closer to potentially offering patients a new first-line maintenance option that could help extend the time they live without their disease progressing.”

References

1. Zepzelca® (lurbinectedin) and atezolizumab (Tecentriq®) combination granted U.S. FDA priority review for first-line maintenance treatment of extensive-stage small cell lung cancer. News release. Jazz Pharmaceuticals. June 10, 2025. Accessed June 10, 2025. https://tinyurl.com/3zetkdv5
2. 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
3. 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. The Lancet. Published online June 2, 2025. doi:10.1016/S0140-6736(25)01011-6