1989MO Lurbinectedin (LUR) in combination with pembrolizumab (PBL) in relapsed small cell lung cancer (SCLC): The phase I/II LUPER study

Previously, we established the recommended phase 2 dose (RP2D) of LUR + PBL in the phase 1 stage of this study (J Clin Oncol. 2022;40(suppl 16):8581). Here we present the results on the efficacy and safety of the RP2D. LUPER (NCT04358237) is a prospective, open-label, uncontrolled, multicenter, phase 1/2 study of LUR in combination with PBL in patients (pts) with relapsed SCLC. Eligible pts were ≥18 years old, with histologically confirmed SCLC, progression after 1L platinum-based chemotherapy, no prior exposure to immunotherapy, ECOG PS of 0-1, and measurable disease as per RECIST 1.1. Pts with treated, asymptomatic, stable brain metastases (BM) were also included. Treatment consisted of LUR dosed at 3.2 mg/m2 IV Q3W in combination with PBL 200 mg IV Q3W until disease progression (PD), unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed overall response rate (ORR) according to RECIST 1.1. Secondary endpoints included investigator-assessed Duration of Response (DoR), Progression-Free Survival (PFS), Overall Survival (OS), and safety as per CTCAE 5.0. A total of 28 pts were included in the study. Median age was 65 years (range 41-78), 46.4% were female, 64.3% had ECOG PS of 1, 51.9% had platinum-free interval < 90 days, 39.3% had LDH > upper normal limit, and 21.4% had BM. At data cutoff (March 31, 2023),11 (39.3%) pts were still on treatment. The median follow-up was 5.7 months (range: 1.0-25.2). Preliminary ORR was 46.4% (95% CI: 29.5–64.2; p<0.001): 2 confirmed CR, 11 PR (9 confirmed) and 4 SD ≥12 weeks. Median DoR was 11.4 months (range: 0-21.2 months), and 2 (7.1%) pts had durable responses > 12 months. Median PFS was 5.3 months (95% CI: 2.7-12.0). Median OS was 11.1 months (95% CI: 6.9-NR). PBL and LUR discontinuation occurred in 3 (10.7%) and 0 pts due to immune-related AE, respectively. The most common grade 3 and 4 treatment-emergent AEs (>20%) were fatigue, neutropenia, nausea and anemia. The LUPER study met its primary endpoint. The combination of LUR + PBL is effective in second-line treatment of SCLC with a manageable safety profile. Further research is warranted to confirm the potential of this combination in SCLC patients.