FDA Approves Lurbinectedin Plus Atezolizumab as First-Line Maintenance Therapy for ES-SCLC

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

The approval was backed by findings from the phase 3 IMforte trial (NCT05091567), which demonstrated statistically significant and clinically meaningful benefits in progression-free survival (PFS) and overall survival (OS) with lurbinectedin plus atezolizumab vs atezolizumab alone in the first-line maintenance therapy setting for patients with ES-SCLC. Primary data from IMforte, presented at the 2025 ASCO Annual Meeting, showed a median PFS by independent review facility (IRF) of 5.4 months (95% CI, 4.2-5.8) with the investigational combination (n = 242) compared with 2.1 months (95% CI, 1.6-2.7) with atezolizumab monotherapy (n = 241; stratified HR, 0.54; 95% CI, 0.43-0.67; 2-sided P< .0001). At 12 months, the IRF-assessed PFS rates were 20.5% vs 12.0%, respectively.1,2

The median OS was 13.2 months (95% CI, 11.9-16.4) vs 10.6 months (95% CI, 9.5-12.2), respectively (stratified HR, 0.73; 95% CI, 0.57-0.95; 2-sided P = .0174). The 12-month OS rates were 56.3% and 44.1%, respectively. 

"The study of lurbinectedin in combination with atezolizumab vs atezolizumab alone is a practice-changing study," Joshua K. Sabari, MD, said in an interview with OncLive®. "It's important to select patients who are fit, have a good performance status, and whose hematologic parameters meet the utilization [criteria for] lurbinectedin and atezolizumab, but it is something I will be using in my clinical practice. Patients who are not eligible for maintenance trials should be offered lurbinectedin plus atezolizumab in the maintenance setting for ES-SCLC."

Sabari is an assistant professor in the Department of Medicine at NYU Grossman School of Medicine and director of High Reliability Organization Initiatives at the Perlmutter Cancer Center in New York, New York.

What Was the Design of the IMforte Trial?

IMforte enrolled 660 patients with ES-SCLC. Patients needed to have received no prior systemic treatment for SCLC, have no central nervous system metastases, and have an ECOG performance status of 0 or 1.2 Patients received induction therapy with atezolizumab plus carboplatin and etoposide every 3 weeks for 4 cycles. Following induction, patients in ongoing complete response (CR), partial response (PR), or stable disease (SD) who had an ECOG performance status of 0 or 1 (n = 483) were randomly assigned to maintenance therapy with lurbinectedin at 3.2 mg/m² intravenously (IV) every 3 weeks plus atezolizumab at 1200 mg IV every 3 weeks, or atezolizumab monotherapy at the same dosing schedule. Patients received treatment until disease progression or unacceptable toxicity. Crossover was not allowed between the arms.

PFS by IRF assessment and OS served as the trial’s coprimary end points. The secondary end points were investigator-assessed PFS, overall response rate (ORR), duration of response (DOR), and safety.

What Were the Additional Key Efficacy Findings From IMforte?

The PFS outcomes per investigator assessment were consistent with those assessed by the IRF. The median investigator-assessed PFS was 5.4 months with lurbinectedin plus atezolizumab vs 2.7 months with atezolizumab monotherapy (stratified HR, 0.55; 95% CI, 0.45-0.68).

Of patients with measurable disease in the lurbinectedin/atezolizumab arm (n = 175), the confirmed ORR (cORR) was 19.4% (95% CI, 13.9%-26.1%); the CR, PR, SD, and progressive disease (PD) rates were 2.3%, 17.1%, 54.9%, and 19.4%, respectively. Of patients with measurable disease in the atezolizumab monotherapy arm (n = 182), the cORR was 10.4% (95% CI, 6.4%-15.8%), and the respective CR, PR, SD, and PD rates were 0.5%, 9.9%, 47.8%, and 4.4%.
The median DOR was 9.0 months (95% CI, 5.5-not estimable [NE]) in the combination arm vs 5.6 months (95% CI, 4.2-NE) in the monotherapy arm.

What Safety Findings From IMforte Are Important to Note?

Any-grade adverse effects (AEs) were reported in 97.1% of patients who received lurbinectedin plus atezolizumab vs 80.8% of patients who received atezolizumab monotherapy. The most common all-cause AEs were nausea (combination arm, 36.4%; monotherapy arm, 4.2%), anemia (31.8%; 6.7%), fatigue (20.2%; 7.9%), decreased appetite (16.9%; 6.7%), decreased platelet count (15.3%; 2.9%), diarrhea (14.0%; 7.5%), vomiting (13.6%; 2.5%), asthenia (12.8%; 6.3%), thrombocytopenia (12.8%; 1.7%), decreased neutrophil count (12.8%; 1.3%), constipation (12.0%; 6.3%), and neutropenia (10.7%; 1.7%).

References

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?utm_medium=email&utm_source=govdelivery
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