While there has been success in initial response to front line therapy for small-cell lung cancer, patients often relapse, creating an important need for systemic therapy after first-line therapy. Furthermore, these patients often develop chemoresistance on disease reoccurrence, promoting a need for non-chemotherapy approaches in second-line therapy.
The LUPER study was designed as a prospective, open-label, phase I/II trial and is assessing the safety/tolerability and clinical response of lurbinectedin in combination with pembrolizumab as second-line therapy for patients with relapsed small-cell lung cancer (SCLC). Lurbinectedin is a novel agent that inhibits the transcription of encoding genes which promotes tumor death and stabilizes the tumor microenvironment. It is currently FDA approved to treat metastatic small-cell lung cancer patients who have progressed on platinum-based chemotherapy. Pembrolizumab is a widely used immunotherapy that binds and blocks programmed cell death protein 1 (PD-1), which helps to allow the immune system to target and destroy cancer cells. The synergistic effects of these two drugs could provide a viable second-line option for these patients.
The trial will be run in two phases, with phase one determining the optimal dosing of lurbinectedin with a fixed dose of pembrolizumab and phase two determining the efficacy at the recommended dose from phase one. Eligible patients must have histologically confirmed SCLC, have progressed on a previous chemotherapy-containing regimen, have had no previous immunotherapy treatment, have an ECOG performance status of 0-1, and have measurable disease per RECIST 1.1. Of note, patients with treated, stable, and asymptomatic brain metastases are also eligible to participate in the trial.
Preliminary safety results were shared at the American Society of Clinical Oncology (ASCO) Meeting 2022. The results from 13 patients from three hospitals enrolled in the study were reported. In terms of patient characteristics, there was a median age of 66 years, 6.2% were female, 61.5% had ECOG PS of 1, 38.5% had platinum-free interval < 90 days, 30.8% had LDH > upper normal limit, and 15.4% had brain metastases. In dose level 1 (2.4mg/m2) there was one dose limiting toxicity (grade 3 asthenia) and one grade 4 neutropenia that lasted greater than 3 days. No dose limiting toxicities were experience in dose level 2 (3.2mg/m2). At data cutoff there were 5 patients still on treatment. One patient had to discontinue treatment due to COVID-19 and two patients discontinued due to immune-related adverse events. Responses were seen in both dose levels with an overall response rate of 30.8%.
“The LUPER trial presents a unique opportunity for patients with relapsed small-cell lung cancer as it combines immunotherapy with chemotherapy for a patient population that has not had therapeutic advances in the last 20 years.” Antonio Calles, MD, from Hospital General Universitario Gregorio Marañón
Trials that explore treatment regimens for patients with unmet needs are of great importance. Contact us if you want to learn more about this trial!