FDA Grants Priority Review for Lurbinectedin/Atezolizumab in ES-SCLC
FDA prioritizes review of lurbinectedin and atezolizumab for first-line maintenance therapy in extensive-stage small cell lung cancer, promising improved survival rates.
US FDA
- The FDA granted priority review to the combination of lurbinectedin (Zepzelca) and atezolizumab (Tecentriq) as a first-line maintenance therapy for extensive-stage small cell lung cancer (ES-SCLC), with a Prescription Drug User Fee Act (PDUFA) target action date of October 7, 2025.
- This priority review is based on positive data from the phase 3 IMforte study (NCT05091567), which demonstrated statistically significant and clinically meaningful improvements in both progression-free survival (PFS) and overall survival (OS) for the lurbinectedin and atezolizumab combination.
- This combination offers a potential new treatment paradigm for patients with ES-SCLC by extending disease control and improving survival, with a manageable safety profile consistent with the known effects of each agent.
The FDA has granted priority review to the supplemental new drug application (sNDA) for lurbinectedin in combination with atezolizumab as a first-line maintenance treatment for patients with ES-SCLC. This designation underscores the significant unmet medical need in ES-SCLC and the potential for this combination therapy to offer a meaningful clinical advancement. The PDUFA target action date for the FDA's decision is set for October 7, 2025.1
Priority review is awarded to applications for drugs that, if approved, would represent a significant improvement in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions. For patients with ES-SCLC, a highly aggressive and rapidly progressing malignancy, new and more effective treatment paradigms are urgently needed. Despite recent advances with the integration of immunotherapy, long-term survival rates for ES-SCLC remain poor, with a 5-year relative survival rate of approximately 7%.2
The sNDA submission is supported by compelling data from the phase 3 IMforte study, a global, randomized, open-label, multicenter trial that evaluated lurbinectedin plus atezolizumab vs atezolizumab alone as maintenance therapy.1 Patients in the IMforte trial had completed 4 cycles of induction therapy with carboplatin, etoposide, and atezolizumab and had not experienced disease progression.
Small cell lung cancer: © Констянтин Батыльчук- stock.adobe.com
Results from the IMforte trial, which were recently presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in The Lancet, demonstrated statistically significant and clinically meaningful improvements in both PFS and OS for the combination arm. After a median follow-up of 15 months, the median PFS for the lurbinectedin and atezolizumab combination was 5.4 months (95% CI, 4.2-5.8), compared with 2.1 months (95% CI, 1.6-2.7) for atezolizumab monotherapy as assessed by an independent review facility. This translated to a 46% reduction in the risk of disease progression or death (HR, 0.54; 95% CI, 0.43-0.67; P <.0001).3
The median OS was 13.2 months (95% CI, 11.9-16.4) for the lurbinectedin and atezolizumab arm vs 10.6 months (95% CI, 9.5-12.2) for the atezolizumab arm. This represents a 27% reduction in the risk of death (HR, 0.73; 95% CI: 0.57-0.95; P=.0174). These results signify a potential shift in the first-line maintenance landscape for ES-SCLC, offering a pathway to extend disease control and improve patient outcomes.
The safety profile of the lurbinectedin and atezolizumab combination was consistent with the known profiles of each agent. While treatment-related adverse events (TRAEs) were more frequent in the combination arm (83.5% vs 40.0% for atezolizumab monotherapy), and grade 3 or 4 events were also higher (25.6% vs 5.8%), these events were generally manageable. Discontinuation rates due to TRAEs were low (6.2% for combination vs 3.3% for monotherapy), suggesting that the regimen is tolerable in the maintenance setting. No new or unexpected safety signals were identified.
Lurbinectedin is an alkylating agent that works by binding to DNA, disrupting cell cycle progression and leading to cell death. It received accelerated FDA approval in June 2020 for patients with metastatic SCLC with disease progression on or after platinum-based chemotherapy.1 Atezolizumab is an immune checkpoint inhibitor targeting PD-L1, which is already a component of standard first-line induction therapy for ES-SCLC. The synergy observed in preclinical models and now in the IMforte trial, combining the cytotoxic effects of lurbinectedin with the immune-modulating effects of atezolizumab, provides a strong biological rationale for this combination.
