The LUPER study evaluates rubicatin/rubitin combined with pembrolizumab in the treatment of relapsed small cell lung cancer

Based on the results of the Phase 1/2 LUPER study, Rubicatin/Lurbinectedin combined with pembrolizumab showed promising efficacy in patients with recurrent small cell lung cancer (SCLC). Evaluating combination therapies is important because second-line treatment options after chemotherapy are limited for patients with SCLC. The study evaluated the safety and efficacy of rubicatin plus pembrolizumab in patients with relapsed SCLC who had not received immunotherapy and was designed to prevent early progression and achieve sustained responses.

This single-arm, open-label study was conducted at multiple centers. Phase 1 established the recommended Phase 2 doses of 3.2 mg/m2 of rubicatin and 200 mg of pembrolizumab intravenously every 3 weeks. The primary endpoint of Phase 2 is investigator-confirmed objective response rate (ORR). Secondary endpoints of the study include duration of response, progression-free survival (PFS), overall survival (OS) and safety. If the patient's chemotherapy-free interval≥90 days, the patient is classified as platinum-sensitive, and if <90 days, the patient is classified as platinum-resistant.

Phase 2 included 28 patients, half of whom were platinum-resistant. The response rate was 46.4% (95% CI, 27.5-66.1; P<0.001), with three complete responses, including two complete metabolic responses after completion of 35 cycles of treatment. The median duration of response was 7.8 months, with 40% of patients maintaining a response for at least one year. The median PFS was 4.6 months and the median OS was 10.5 months. The researchers found that the median disease-free survival of patients who were sensitive to platinum was 8 months, which was significantly higher than the median disease-free survival of 2.8 months for patients who were resistant to platinum (P=0.012). In addition, platinum-sensitive patients had a numerical advantage compared with resistant patients, with OS15.7 months vs. 7.1 months, P=0.058.

Nearly three-quarters (71.4%) of patients experienced grade ≥3 treatment-related adverse events. The investigators reported that transient neutropenic events were the most common and noted that immune-related adverse events were consistent with previous pembrolizumab studies.

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

Reference materials:https://www.lungcancerstoday.com/post/luper-study-evaluates-lurbinectedin-plus-pembrolizumab-in-relapsed-sclc