First-Line Lurbinectedin Plus Atezolizumab Maintenance Under Priority Review for ES-SCLC

ES-SCLC | Image by: Ashling Wahner &

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The FDA has granted priority review to the supplemental biologics license application (sNDA) seeking the approval of the combination of lurbinectedin (Zepzelca) and atezolizumab (Tecentriq) for the first-line maintenance treatment of patients with extensive-stage small cell lung cancer (ES-SCLC) whose disease has not progressed after frontline induction therapy with atezolizumab, carboplatin, and etoposide.1

The FDA has set a target action date under the Prescription Drug User Fee Act of October 7, 2025.

The sNDA was supported by data from the phase 3 IMforte trial (NCT05091567), which showed statistically significant and clinically meaningful improvements in both its primary end points of progression-free survival (PFS) assessed by an independent review facility (IRF) and overall survival (OS) with lurbinectedin plus atezolizumab vs atezolizumab alone as first-line maintenance therapy for patients with first-line ES-SCLC. Primary data from IMforte were presented at the 2025 ASCO Annual Meeting.1,2 The median PFS was 5.4 months (95% CI, 4.2-5.8) with the combination (n = 242) vs 2.1 months (95% CI, 1.6-2.7) with the monotherapy (n = 241; stratified HR, 0.54; 95% CI, 0.43-0.67; 2-sided P < .0001). The median OS in the respective arms was 13.2 months (95% CI, 11.9-16.4) vs 10.6 months (95% CI, 9.5-12.2; stratified HR, 0.73; 95% CI, 0.57-0.95; 2-sided P = .0174).

“The FDA’s priority review designation for [lurbinectedin] in combination with atezolizumab as a first-line maintenance treatment highlights the urgent need for new approaches and the potential benefit of [lurbinectedin] for patients with ES-SCLC, a disease with limited therapeutic options and high unmet need,” Rob Iannone, MD, MSCE, executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals, stated in a news release.1 “We are pleased to have received this review designation after presenting the IMforte trial data at ASCO 2025 with simultaneous publication in The Lancet. Together, these milestones bring us a step closer to potentially offering patients a new first-line maintenance option that could help extend the time they live without their disease progressing.”

IMforte enrolled 660 patients with ES-SCLC who had received no prior systemic treatment for the disease, had no central nervous system metastases, and had an ECOG performance score of 0 or 1.2 Patients received induction therapy with atezolizumab, carboplatin, and etoposide every 3 weeks for 4 cycles. After induction, patients who were in ongoing complete response (CR), partial response (PR), or stable disease (SD) and had an ECOG performance status of 0 or 1 (n = 483) were randomly assigned to receive maintenance therapy with lurbinectedin plus atezolizumab or atezolizumab monotherapy. Patients were treated until progressive disease (PD) or unacceptable toxicity. Notably, no crossover was allowed between the arms.

Patients received lurbinectedin at 3.2 mg/m2 intravenously (IV) every 3 weeks. Atezolizumab was administered at 1200 mg IV every 3 weeks.

Key secondary end points included PFS assessed by the investigator, overall response rate (ORR), duration of response (DOR), and safety.

The 12-month IRF-assessed PFS rates were 20.5% in the combination arm vs 12.0% in the monotherapy arm. The investigator-assessed PFS outcomes were consistent with the IRF-assessed PFS outcomes, with medians of 5.4 months with the combination vs 2.7 months with the monotherapy (stratified HR, 0.55; 95% CI, 0.45-0.68).

The 12-month OS rates were 56.3% and 44.1% in the respective arms.

Among patients with measurable disease in the combination arm (n = 175), the confirmed ORR (cORR) was 19.4% (95% CI, 13.9%-26.1%), including CR, PR, SD, and PD rates of 2.3%, 17.1%, 54.9%, and 19.4%, respectively. The median DOR in this arm was 9.0 months (95% CI, 5.5-not estimable [NE]).

Among patients with measurable disease in the monotherapy arm (n = 182), the cORR was 10.4% (95% CI, 6.4%-15.8%), including CR, PR, SD, and PD rates of 0.5%, 9.9%, 47.8%, and 4.4%, respectively. The median DOR in this arm was 5.6 months (95% CI, 4.2-NE).

Any-grade adverse effects (AEs) occurred in 97.1% of patients in the lurbinectedin/atezolizumab arm vs 80.8% of those in the atezolizumab monotherapy arm. The most common all-cause AEs in these respective arms were nausea (36.4%; 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. Zepzelca (lurbinectedin) and atezolizumab (Tecentriq) combination granted U.S. FDA priority review for first-line maintenance treatment of extensive-stage small cell lung cancer. News release. Jazz Pharmaceuticals. June 10, 2025. Accessed June 10, 2025. https://investor.jazzpharma.com/news-releases/news-release-details/zepzelcar-lurbinectedin-and-atezolizumab-tecentriqr-combination
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