LUPER Study Evaluates Lurbinectedin Plus Pembrolizumab in Relapsed SCLC

Lurbinectedin plus pembrolizumab demonstrated “promising efficacy” in patients with relapsed small cell lung cancer (SCLC), according to results from the phase 1/2 LUPER study.

Antonio Calles, MD, Hospital General Universitario Gregorio Marañón, and colleagues conducted the study and published their findings in the Journal of Thoracic Oncology.

It was important to assess the combination therapy because there are “limited second-line treatment options after chemotherapy” for patients with SCLC. Dr. Calles and colleagues evaluated the safety and efficacy of lurbinectedin plus pembrolizumab in patients with relapsed SCLC who had not received prior immunotherapy, “aiming to prevent early progression and achieve sustained responses,” they explained.

The single-arm, open-label study was conducted at multiple centers. Phase 1 established the recommended phase 2 dose of lurbinectedin 3.2 mg/m² and pembrolizumab 200 mg via IV every 3 weeks. The primary endpoint of phase 2 was the investigator-confirmed objective response rate (ORR). The secondary endpoints of the study included duration of response, progression-free survival (PFS), overall survival (OS), and safety. Patients were categorized as platinum-sensitive if they had a chemotherapy-free interval ≥90 days or platinum-resistant if it was <90 days.

Phase 2 included 28 patients, half of whom were resistant to platinum. The ORR was 46.4% (95% CI, 27.5-66.1; P<0.001), with three complete responses, including two complete metabolic responses after treatment completion at 35 cycles. The median duration of response was 7.8 months and 40% of patients maintained their responses for at least a year.

The median PFS was 4.6 months, with a median OS of 10.5 months. The study investigators found that patients who were sensitive to platinum had a median PFS of 8 months, significantly higher than the median PFS of 2.8 months in those resistant to platinum (P=0.012). In addition, patients who were sensitive to platinum had “numerically superior OS,” compared to those who were resistant (15.7 vs 7.1 months, P=0.058).

Grade ≥3 treatment-related adverse events occurred in nearly three-quarters (71.4%) of patients. Transient neutropenia events were the most common, the study investigators reported, noting that “immune-related adverse events were consistent with prior pembrolizumab studies.”

Based on these findings, Dr. Calles and colleagues concluded that the combination “showed promising efficacy in relapsed SCLC, particularly for platinum-sensitive patients, with a known and manageable safety profile” and that the results “support further exploration of this combination in SCLC treatment.”

Reference

Calles A, Navarro A, Gaston B, et al. Lurbinectedin plus pembrolizumab in relapsed small cell lung cancer (SCLC): the phase I/II LUPER study. Journal of Thoracic Oncology. Published online February 1, 2025. doi:https://doi.org/10.1016/j.jtho.2025.02.005