Lurbinectedin plus pembrolizumab in relapsed small cell lung cancer (SCLC): the phase I/II LUPER study.

Abstract

Introduction: Small-cell lung cancer (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 (RP2D). The primary endpoint of phase II was investigator-confirmed objective response rate (ORR). Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Patients were categorized as platinum-sensitive (chemotherapy-free interval ≥90 days) or platinum-resistant (<90 days).

Results: The RP2D was 3.2 mg/m² lurbinectedin and 200 mg pembrolizumab IV every 3 weeks. Phase II included 28 patients, 50% were platinum-resistant. ORR was 46.4% (95% CI, 27.5-66.1; p<0.001), including three complete responses, with 2 complete metabolic responses post-treatment completion at 35 cycles. Median DoR was 7.8 months, with 40% maintaining responses for ≥12 months. Median PFS was 4.6 months, and median OS was 10.5 months. Platinum-sensitive patients had significantly better PFS (8.0 vs. 2.8 months, p=0.012) and numerically superior OS (15.7 vs. 7.1 months, p=0.058). Grade ≥3 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 showed 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.