CHMP Recommends Approval of First-Line Lurbinectedin Plus Atezolizumab Maintenance for ES-SCLC

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended the approval of lurbinectedin (Zepzelca) in combination with atezolizumab (Tecentriq) for the first-line maintenance treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) whose disease has not progressed following standard induction therapy.¹

This recommendation was backed by findings from the phase 3 IMforte trial (NCT05091567), in which patients who received lurbinectedin plus atezolizumab achieved a 46% reduction in the risk of disease progression or death and a 27% reduction in the risk of death compared with patients who received atezolizumab alone. The median progression-free survival (PFS) per independent review facility (IRF) was 5.4 months (95% CI, 4.2-5.8) with lurbinectedin plus atezolizumab (n = 242) vs 2.1 months (95% CI, 1.6-2.7) with atezolizumab alone (n = 241; stratified HR, 0.54; 95% CI, 0.43-0.67; 2-sided P < .0001).² The respective 12-month IRF-assessed PFS rates were 20.5% and 12.0%.

Furthermore, the median overall survival (OS) was 13.2 months (95% CI, 11.9-16.4) in the lurbinectedin arm compared with 10.6 months (95% CI, 9.5-12.2) in the control arm (stratified HR, 0.73; 95% CI, 0.57-0.95; 2-sided P = .0174). At 12 months, the respective OS rates were 56.3% and 44.1%.

“This positive opinion represents a significant step forward in providing patients in Europe with access to an innovative therapy for a disease with a particularly poor prognosis,” Luis Paz-Ares, MD, PhD, head of the Medical Oncology Service at the 12 de Octubre University Hospital in Madrid, Spain, as well as principal investigator of the IMforte trial, stated in a news release.¹ “For the first time in this maintenance context, an improvement in OS and PFS has been demonstrated, marking a milestone in the [management] of this disease. For health care professionals, this advancement provides a new treatment option to offer our patients.”

What was the design of the IMforte trial?

This trial enrolled patients with ES-SCLC who had received no prior systemic treatment for SCLC, had no central nervous system metastases, and had an ECOG performance status of 0 or 1.² Patients received 4 cycles of induction therapy consisting of atezolizumab, carboplatin, and etoposide every 3 weeks. After induction, patients who had ongoing complete response, partial response, or stable disease and an ECOG performance status of 0 or 1 (n = 483) were randomly assigned to receive maintenance therapy with intravenous (IV) lurbinectedin at 3.2 mg/m² every 3 weeks in combination with atezolizumab at 1200 mg IV every 3 weeks, or atezolizumab monotherapy at the same dosing schedule.

The coprimary end points were PFS by IRF and OS. Secondary end points included investigator-assessed PFS, overall response rate, duration of response, and safety.

What is the safety profile of lurbinectedin plus atezolizumab as first-line maintenance therapy in ES-SCLC?

The most common all-cause adverse effects among patients who received lurbinectedin plus atezolizumab included nausea (36.4%), anemia (31.8%), fatigue (20.2%), decreased appetite (16.9%), decreased platelet count (15.3%), diarrhea (14.0%), vomiting (13.6%), asthenia (12.8%), thrombocytopenia (12.8%), decreased neutrophil count (12.8%), constipation (12.0%), and neutropenia (10.7%).

“The CHMP’s positive opinion represents a very important milestone in facilitating access for European patients to a new therapeutic option,” Luis Mora, managing director of PharmaMar, added in the news release.¹ “It also represents important recognition of our Company’s commitment to research and development of innovative new compounds.”

What other regulatory updates for lurbinectedin in SCLC are important to note?

Following a positive opinion from the EMA’s Committee for Orphan Medicinal Products, lurbinectedin was also approved in Europe as an orphan medicinal product for the treatment of patients with SCLC.

In October 2025, the FDA approved lurbinectedin plus atezolizumab or atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza) as maintenance therapy for adult patients with ES-SCLC whose disease has not progressed following first-line induction therapy with atezolizumab or atezolizumab and hyaluronidase, carboplatin, and etoposide.³ This regulatory decision was also supported by data from IMforte.

References

1. PharmaMar receives recommendation for the approval from the European Medicines Agency for Zepzelca (lurbinectedin) for the treatment of extensive-stage small cell lung cancer in combination with the immunotherapy atezolizumab. News release. PharmaMar. March 27, 2026. Accessed March 30, 2026. https://pharmamar.com/en/pharmamar-receives-recommendation-for-the-approval-from-the-european-medicines-agency-for-zepzelca-lurbinectedin-for-the-treatment-of-extensive-stage-small-cell-lung-cancer-in-combination-with/
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. FDA approves lurbinectedin in combination with atezolizumab or atezolizumab and hyaluronidase-tqjs for extensive-stage small cell lung cancer. FDA. October 2, 2025. Accessed March 30, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lurbinectedin-combination-atezolizumab-or-atezolizumab-and-hyaluronidase-tqjs-extensive?utm_medium=email&utm_source=govdelivery