Lurbinectedin Combo Approved by FDA for Extensive-Stage Small Cell Lung Cancer

Extensive-stage small cell lung cancer (ES-SCLC) can now be treated with a newly approved combination. Lurbinectedin (Zepselca; Jazz Pharmaceuticals, Inc.) has received FDA approval for use in ES-SCLC in combination with atezolizumab (Tecentriq; Genentech Inc.) or atezolizumab and hyaluronidase (Tecentriq Hybreza; Genentech Inc.).

The treatment will primarily be used in patients who, after first-line induction therapy, have not experienced any progression of their condition. Patients are recommended to take a lurbinectedin dose of 3.2 mg/m² by an intravenous infusion every 3 weeks until either unacceptable toxicity or disease progression. This in combination with an atezolizumab dose of either 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks through an intravenous infusion. If a patient uses atezolizumab in combination with hyaluronidase, the dose should be 1875 mg of atezolizumab and 30,000 units of hyaluronidase delivered every 3 weeks through subcutaneous injection.

The approval was based on the IMforte trial, which tested the efficacy of lurbinectedin plus atezolizumab in treating ES-SCLC in a phase 3 trial.2 The study took place across 96 hospitals and medical centers in Belgium, Greece, Germany, Hungary, Italy, Mexico, Poland, South Korea, Spain, Taiwan, Türkiye, the United Kingdom, and the US. All patients were treatment-naïve for ES-SCLC and were aged 18 years and older. The participants were split into 2 groups, where the first received a 1200 mg dose of atezolizumab alone and the second received a 3.2 mg/m² dose of lurbinectedin plus a 1200 mg dose of atezolizumab. Progression-free and overall survival were the primary end points of the study.

There were 483 patients who were included in the study and received the treatments between May 24, 2022, and April 30, 2024. The researchers found that overall survival (stratified HR, 0.73; 95% CI, 0.57-0.95) and progression-free survival (stratified HR, 0.54; 95% CI, 0.43-0.67) were both higher in the group that took the combination therapy.

Adverse events were more common in the combination group, with 38% of those on the combination therapy reporting a grade 3 or 4 adverse event compared with 22% of those taking atezolizumab alone. Anemia (8%), decreased platelet count (7%), and decreased neutrophil count (7%) were the most common grade 3 or 4 adverse events reported in those who used the combination therapy.

Lurbinectedin was found to be safe overall but includes warnings for myelosuppression, extravasation resulting in tissue necrosis, embryo-fetal toxicity, hepatotoxicity, and rhabdomyolysis. Severe and fatal immune-mediated adverse reactions, complications of allogeneic hematopoetic stem cell transplantation, infusion-related reactions, and embryo-fetal toxicity are found on the label for atezolizumab alone and in combination with hyaluronidase.

"Small cell lung cancer is an aggressive and devastating disease; at the time of diagnosis, the large majority of patients have already progressed to extensive-stage disease, and only 1 out of 5 survive longer than 2 years," said Luis Paz-Ares, MD, PhD, the principal investigator of IMforte, after presenting the data for IMforte at the 2025 American Society of Oncology Annual Meeting.³ "The IMforte results are very encouraging, showing a potentially practice-changing option that could improve survival for patients with a very high unmet need."

References

1. 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 October 2, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lurbinectedin-combination-atezolizumab-or-atezolizumab-and-hyaluronidase-tqjs-extensive

2. 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 randomized, multicenter, open-label, phase 3 trial. Lancet. 2025;405(10495):2129-2143. doi:10.1016/S0140-6736(25)01011-6

3. Jazz Pharmaceuticals announces Zepzelca (lurbinectedin) and atezolizumab (Tecentriq) combination significantly improves survival as first-line maintenance therapy for extensive-stage small cell lung cancer. News release. Jazz Pharmaceuticals. June 2, 2025. Accessed October 2, 2025. https://investor.jazzpharma.com/news-releases/news-release-details/jazz-pharmaceuticals-announces-zepzelcar-lurbinectedin-and