FDA Approves Lurbinectedin/Atezolizumab Maintenance Therapy in ES-SCLC

Based on results from IMforte, combination maintenance therapy for ES-SCLC with lurbinectedin plus atezolizumab has received FDA approval.

The FDA has approved the use of lurbinectedin (Zepzelca) plus atezolizumab or atezolizumab (Tecentriq) and hyaluronidase-tqjs (Tecentriq Hybreza) for the treatment of patients with extensive-stage small cell lung cancer (ES-SCLC) whose disease has not progressed following frontline induction therapy with atezolizumab or subcutaneous atezolizumab, carboplatin, and etoposide.¹

How Effective Is Lurbinectedin With Atezolizumab?

The approval is based on results from the phase 3, randomized, multicenter, open-label IMforte trial (NCT05091567). End points included overall survival (OS) and progression-free survival (PFS), assessed by independent review facility (IRF) per RECIST v1.1. OS was 13.2 months (95% CI, 11.9-16.4) in the lurbinectedin/atezolizumab arm and 10.6 months (95% CI, 9.5-12.2) in the atezolizumab arm (hazard ratio [HR] 0.73; 95% CI, 0.57-0.95; two-sided P = .0174).

Median PFS was 5.4 months (95% CI, 4.2-5.8) in the lurbinectedin/atezolizumab arm vs 2.1 months (95% CI, 1.6-2.7) in the atezolizumab arm (HR, 0.54; 95% CI, 0.43-0.67; two-sided P < .0001). These end points were measured from the time of randomization after completion of induction therapy.

The recommendation for this approval is as follows:

• Lubrinectedin: 3.2 mg/m²via IV every 21 days
• Atezolizumab:
  • 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks if via IV, OR
  • 1875 mg of atezolizumab with 30,000 units of hyaluronidase every 3 weeks if administered subcutaneously

What Patients Were Observed in IMforte?

Researchers of IMforte observed 483 patients with ES-SCLC who did not have disease progression after finishing 4 cycles of induction treatment with atezolizumab, carboplatin, and etoposide. Patients were randomized 1:1 to receive either lurbinectedin with atezolizumab delivered via IV or IV atezolizumab alone until either disease progression or unacceptable toxicity.

Lurbinectedin/Atezolizumab: What Do We Know?

Results from IMforte were presented at the 2025 American Society of Clinical Oncology Annual Meeting in May, where researchers shared a manageable safety profile associated with the combination therapy.²

“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 [SOC] for first-line maintenance therapy in patients with this aggressive and difficult-to-treat disease,” Luis Paz-Ares, MD, PhD, of Hospital Universitario 12 de Octubre, H12O-CNIO Lung Cancer Unit, Universidad Complutense and Ciberonc, in Madrid, Spain, said in a press briefing ahead of the meeting.

Lurbinectedin’s label includes warnings for myelosuppression, hepatotoxicity, extraversion leading to tissue necrosis, rhabdomyolysis, and embryo-fetal toxicity. Atezolizumab’s label includes warnings for infusion-related reactions, complications of allogeneic HSCT, embryo-fetal toxicity, and immune-mediated adverse effects (AEs), which can be fatal.

“The safety profile of lurbinectedin plus atezolizumab was manageable, with mostly low-grade AEs and low treatment discontinuation rates,” Paz-Ares said. “No clinically meaningful increase in immune-related AEs was observed [with the addition of lurbinectedin],” he noted.

The most frequent AEs, occurring in 10% or more of those in the lurbinectedin/atezolizumab and atezolizumab arms, were nausea (36.4% vs 4.2%), anemia (31.8% vs 6.7%), fatigue (20.2% vs 7.9%), decreased appetite (16.9% vs 6.7%), decreased platelet count (15.3% vs 2.9%), diarrhea (14.0% vs 7.5%), vomiting (13.6% vs 2.5%), asthenia (12.8% vs 6.3%), thrombocytopenia (12.8% vs 1.7%), decreased neutrophil count (12.8% vs 1.3%), constipation (12.0% vs 6.3%), and neutropenia (10.7% vs 1.7%).

Lubrinectedin is an alkylating chemotherapy, and atezolizumab is a PD-L1-targeting immune checkpoint inhibitor.

Reference

1. FDA approves lurbinectedin in combination with atezolizumab or atezolizumab and hyaluronidase-tqjs for extensive-stage small cell lung cancer. 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. 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. Presented at: 2025 ASCO Annual Meeting; May 30-June 3, 2025; Chicago, IL. Abstract 8006.