Preliminary Results Show Second-line Lurbinectedin Plus Pembrolizumab Safe, Effective in Relapsed SCLC


Preliminary findings of data from the phase 1/2 LUPER study demonstrate that treatment with lurbinectedin combined with pembrolizumab elicits promising efficacy in patients with metastatic small-cell lung cancer that has failed to respond to chemotherapy.

The second-line use of lurbinectedin (Zepzelca) in combination with pembrolizumab (Keytruda) was associated with a manageable safety profile and early efficacy in a small population of patients with relapsed small-cell lung cancer (SCLC), according to results of the phase 1/2 LUPER study (NCT04358237) presented at the 2022 American Society of Clinical Oncology.1

Treatment with lurbinectedin plus pembrolizumab resulted in an overall response rate (ORR) of 30.8% among the 13 patients [median age, 66 years (range, 43-78); 54% male] enrolled onto the trial across 3 hospitals in Spain.

As of March 10, 2022, 4 patients remained on treatment. The preliminary findings showed that the median duration of treatment was 3.1 [range, 0-14.6] months. Moreover, a median duration of response (DOR) has not yet been reached. Seventy-five percent of patients were shown to derive a response to treatment at 9 months [95% CI; 42.6%-100%).

Previously, the Food and Drug Administration (FDA) approved the use of lurbinectedin for the treatment of adults with metastatic SCLC with disease progression on or following platinum-based chemotherapy.2

Those findings demonstrated that lurbinectedin monotherapy demonstrated an ORR of 35% and a median DOR of 5.3 months per investigator assessment.

Here, the study authors presented preliminary data from the early-phase trial that, according to the investigators, is assessing the safety, tolerability and efficacy of lurbinectedin plus pembrolizumab in this patient population for the first time.

Enrolled patients have to be aged 18 years or older, have an ECOG Performance Status of 0-1 and have measurable disease per RECIST v.1.1. Additionally, patients must have had progression to a chemotherapy-containing regimen at least 4 weeks prior to enrolling into the study.

Patients were excluded from enrollment if they had received prior treatment with an immunotherapy. However, patients with stable, asymptomatic and treated brain metastases are allowed onto the trial.

The aim of the phase 1 portion of the trial was to identify a maximum tolerated dose as well as the recommended phase 2 dose of the combination treatment. As for the phase 2 portion of the trial, the goal is to analyze efficacy of the study treatment per ORR. Additional endpoints include safety, preliminary efficacy and the pharmacokinetics of the combination.

Patients enrolled into the phase 1 trial were administered 200 mg of pembrolizumab every 3 weeks (Q3W) plus a starting dose of 2.4 mg/m2 of lurbinectedin Q3W. A grade 3 fatigue occurred in the phase 1 portion of the trial. That adverse event (AE) caused the patient to have a dose reduction.

After further evaluation, the investigators identified the recommended phase 2 dose as 3.2 mg/m2 of lurbinectedin and 200 mg of pembrolizumab administered Q3W.

Early results showed that 84.6% of the population reported experiencing an any-grade treatment-emergent AE. The most common TEAE that was hematologic was neutropenia (53.9% any grade). Fatigue of any-grade severity (76.9%) was the most common non-hematologic TEAE. Of note, there was one patient death, however it was attributed to COVID-19.

“This combination warrants further confirmation in the ongoing expansion phase 2 [trial] with additional biomarker analysis of efficacy,” the study authors concluded in a poster detailing the findings.


  1. Calles A, Navarro A, Doger B, et al. A phase 1/2 trial of lurbinectedin (L) in combination with pembrolizumab (P) in relapsed small cell lung cancer (SCLC): The LUPER study. J Clin Oncol. 2022; 40 (suppl 16):8581. doi: doi.10.1200/JCO.2022.40.16_suppl.8581
  2. Jazz Pharmaceuticals announces U.S. FDA accelerated approval of Zepzelca™ (lurbinectedin) for the treatment of metastatic small cell lung cancer. News Release. AstraZeneca. June 15, 2020.
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