Lurbinectedin Yields Responses in Various ES-SCLC Subgroups

Lurbinectedin achieved an ORR of 27% in all patients with extensive-stage small cell lung cancer in the phase 4 Jazz Emerge 402 study.

Lurbinectedin (Zepzelca) was efficacious across various extensive-stage small cell lung cancer (ES-SCLC) patient subgroups, including older patients, those with platinum-resistant disease, and those with central nervous system (CNS) metastases, as shown in results from the phase 4 Jazz Emerge 402 trial (NCT04894591) shared at the International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer.1

In all patients (n = 192), the overall response rate (ORR) was 27% (95% CI, 20%-33%), with 4% achieving complete responses, 22% achieving partial responses, 19% having stable disease, and 38% having progressive disease; the disease control rate (DCR) was 45% (95% CI, 38%-53%), and the median duration of response (DOR) was 4.0 months (95% CI, 3.0-4.9). The median progression-free survival (PFS) was 3.3 months (95% CI, 2.6-4.1).

In second-line (n = 123) and third-line (n = 57) settings, the ORRs were 29% (95% CI, 21%-38%) and 23% (95% CI, 13%-36%), respectively; the DCRs were 46% (95% CI, 37%-56%) and 47% (95% CI, 34%-61%), the median DORs were 3.7 months (95% CI, 2.7-4.8) and 4.7 months (95% CI, 2.7-6.3), and the median PFS was 3.3 months (95% CI, 2.4-4.1) and 3.8 months (95% CI, 2.5-4.9).

Those with a chemotherapy-free interval (CTFI) of less than 90 days (n = 64) and 90 days or longer (n = 97) experienced an ORR of 22% (95% CI, 13%-34%) and 29% (95% CI, 20%-39%), respectively; the DCRs were 41% (95% CI, 29%-54%) and 47% (95% CI, 37%-58%), the median DORs were 3.7 months (95% CI, 2.3-4.8) and 3.5 months (95% CI, 2.6-6.9), and the median PFS was 3.1 months (95% CI, 2.1-4.2) and 3.1 months (95% CI, 2.5-4.2).

In patients younger than 65 years (n = 71) and 65 years or older (n = 121), the ORRs were 27% (95% CI, 17%-39%) and 26% (95% CI, 19%-35%), respectively; the DCRs were 48% (95% CI, 36%-60%) and 44% (95% CI, 35%-53%), the median DORs were 4.7 months (95% CI, 2.6-6.4) and 3.7 months (95% CI, 2.7-6.2), and the median PFS was 4.1 months (95% CI, 2.8-4.5) and 2.9 months (95% CI, 2.3-4.0).

Patients without (n = 150) and with (n = 42) CNS metastases had ORRs of 29% (95% CI, 22%-37%) and 17% (95% CI, 7%-31%), respectively; the DCRs were 49% (95% CI, 40%-57%) and 33% (95% CI, 20%-50%), the median DORs were 4.4 months (95% CI, 3.5-6.3) and 2.7 months (95% CI, 0.7-4.9), and the median PFS was 3.8 months (95% CI, 2.7-4.9) and 2.5 months (2.0-3.5).

Additionally, numerically higher ORRs were reported in those who received treatment in the second line vs third line, in those with a CTFI of 90 days or more, and those without CNS metastases.

The Kaplan-Meier analysis of overall survival (OS) demonstrated that the median OS was 7.6 months (95% CI, 6.6-9.2) in all patients, 7.6 months (95% CI, 6.4-9.4) in patients in the second line, and 7.6 months (95% CI, 5.8-10.8) in patients in the third line. Analysis also showed that of patients in the second line of therapy, those with a CTFI of less than 90 days and 90 days or more had a median OS of 5.8 months (95% CI, 4.6-7.2) and 11.9 months (95% CI, 7.9-14.6), respectively.

“Lurbinectedin demonstrated clinically meaningful effectiveness across subgroups, including as a [third-line] treatment and in older patients [65 years or older], those with platinum-resistant disease [and a CTFI of less than 90 days], and those with CNS metastases; this contrasts with the poor outcomes observed with topotecan [Hycamtin] in these subgroups,” wrote Balazs Halmos, MD, professor in the Department of Oncology and associate director of clinical science at Montefiore Medical Center of Albert Einstein College of Medicine, with coauthors in the presentation.1,2 “Lurbinectedin was generally well tolerated in clinical practice, with no new safety signals and low rates of dose reductions and treatment discontinuations due to adverse events [AEs].”

Jazz Emerge 402 was a prospective, single-arm, real-world, multicenter trial that enrolled a total of 265 patients with ES-SCLC who received treatment with lurbinectedin per local labeling in the US or Canada. All patients were assessed by a physician and prescribed lurbinectedin per routine treatment practice prior to study enrollment.

The trial’s primary end point was investigator-assessed ORR per RECIST v1.1 criteria. Secondary end points included PFS, DOR, DCR, OS, incidence and severity of AEs, and reasons for treatment discontinuation or dose reduction/delay.

Regarding safety, any AE occurred in 60% of patients, with the most common including anemia (8%), neutropenia (8%), thrombocytopenia (6%), and nausea (6%). Serious AEs occurred in 37% of patients, with treatment-related serious AEs occurring in 11%. AEs led to treatment discontinuation and dose reduction in 7% and 5%, respectively.

It was noted that approximately one-third of patients were administered granulocyte colony-stimulating factor prophylaxis.

References

1. Halmos B, Lammers P, Liu G, et al. Real-world effectiveness and safety of lurbinectedin for small cell lung cancer: updates from Jazz EMERGE 402. Abstract presented at: International Association for the Study of Lung Cancer World Conference on Lung Cancer 2025; September 6-9, 2025; Barcelona, Spain. Abstract P3.13.31.
2. Lambrecht L, Arnold P, Behr J, Mertsch P, Tufman A, Kauffmann-Guerrero D. Topotecan in a real-world small-cell lung cancer cohort: prognostic biomarkers improve selection of patients for second-line treatment. Diagnostics (Basel). 2024;14(14):1572. doi:10.3390/diagnostics14141572