Lurbinectedin Plus Pembrolizumab in Relapsed SCLC: The Phase I/II LUPER Study

Abstract

Introduction: SCLC has limited second-line treatment options after chemotherapy. We assessed the efficacy and safety of lurbinectedin combined with pembrolizumab in relapsed SCLC patients who had not received prior immunotherapy, aiming to prevent early progression and achieve sustained responses. Methods: The LUPER trial (NCT04358237) is a phase I/II, single-arm, open-label, multicenter study. Phase I established the recommended phase II dose. The primary endpoint of phase II was the investigator-confirmed objective response rate. Secondary endpoints included duration of response, progression-free survival (PFS), overall survival (OS), and safety. Patients were categorized as platinum-sensitive (chemotherapy-free interval >= 90 d) or platinum-resistant (<90 d). Results: The recommended phase II dose was 3.2 mg/m(2) lurbinectedin and 200 mg pembrolizumab IV every three weeks. Phase II included 28 patients, 50% of whom were platinum-resistant. The objective response rate was 46.4% (95% confidence interval: 27.5-66.1, p < 0.001), including three complete responses, with two complete metabolic responses post-treatment completion at 35 cycles. The median duration of response was 7.8 months, with 40% of patients maintaining responses for 12 months or longer. The median PFS was 4.6 months, and the median OS was 10.5 months. Platinum-sensitive patients had significantly better PFS (8.0 versus 2.8 mo, p = 0.012) and numerically superior OS (15.7 versus 7.1 mo, p = 0.058). Grade 3 or higher treatment-related adverse events occurred in 71.4% of patients, with transient neutropenia being the most common. Immune-related adverse events were consistent with prior pembrolizumab studies. Conclusions: Lurbinectedin plus pembrolizumab reported promising efficacy in relapsed SCLC, particularly for platinum-sensitive patients, with a known and manageable safety profile. These results support further exploration of this combination in SCLC treatment.