Antonio Calles, MD, Highlights Promising Preliminary Activity of Lurbinectedin and Pembrolizumab in Relapsed SCLC


Early results from the phase 1/2 LUPER study indicated that lurbinectedin in combination with pembrolizumab demonstrated no unexpected toxicities and promising preliminary efficacy in the second line for patients with relapsed small cell lung cancer, according to Antonio Calles, MD.

Antonio Calles, MD, a medical oncologist of the Department of Medical Oncology at Hospital General Universitario Gregorio Marañón

Antonio Calles, MD, a medical oncologist of the Department of Medical Oncology at Hospital General Universitario Gregorio Marañón

Preliminary findings indicated that second-line treatment with lurbinectedin (Zepzelca) and pembrolizumab (Keytruda) following the progression on platinum-based chemotherapy yielded a manageable safety and potential efficacy in relapsed small-cell lung cancer (SCLC), according to Antonio Calles, MD.

The combination was assessed as part of the phase 1/2 LUPER study (NCT04358237), the preliminary findings of which were presented at the 2022 American Society of Clinical Oncology (ASCO). The population of 13 patients were treated for a median of 3.1 months with a relative dose intensity of 90.6% for lurbinectedin and 90.8% for pembrolizumab. The overall response rate was 30.8% and the median duration of response was not reached. Seventy-five percent of patients were responders at 9 months.

The recommended phase 2 dose was 3.2 mg/m2 of lurbinectedin and 200 mg of intravenous pembrolizumab taken once every 3 weeks. Although the research is still in its early stages, Calles detailed how it might impact the treatment landscape in the future and fulfill unmet need.

“The treatment landscape of SCLC will hopefully evolve quickly,” he stated. “[Currently,] the standard-of-care is chemoimmunotherapy in the first-line setting. This trial was designed before the approval of any of these [therapies.] There is still room for treatment with chemotherapy/immunotherapy in the second-line setting such as patients with locally advanced disease who relapse or patients who for any reason were not treated with chemotherapy/immunotherapy in the first-line setting. Again, we don't know how to treat patients after failure of first-line chemotherapy/immunotherapy. This combination could be a potential option in the future to treat these patients.”

In a discussion with CancerNetwork®, Calles, a medical oncologist of the Department of Medical Oncology at Hospital General Universitario Gregorio Marañón, highlighted preliminary safety associated with the combination regimen and unmet needs in patients with advanced disease following treatment with platinum-based chemotherapy.

CancerNetwork®: Could you tell me about the rationale for assessing lurbinectedin and pembrolizumab in relapsed small-cell lung cancer?

Calles: Lurbinectedin is a new agent that works in the trans-activation [transcript] factors and also modulates the tumor microenvironment. It is currently FDA-approved for the treatment of patients who relapse on or after platinum-based chemotherapy. This is a phase 1/2 trial assessing the safety and preliminary efficacy of the combination of pembrolizumab, an anti-PD1 agent, with lurbinectedin.

What were the key safety findings that read out at this year’s meeting?

We were able to find the maximum tolerated dose. We also found that we can use full doses of both lurbinectedin and pembrolizumab. There were no safety signals with a well-known toxicity profile for both agents. For pembrolizumab, the rate of immune-related adverse [effects is consistent] with what is known for this agent in this setting. And for lurbinectedin, the main toxicity was neutropenia and fatigue, which was also in the range for what is known for single-agent lurbinectedin. There were no unexpected toxicities with the combination.

Where do you see research efforts being focused from here?

Our main goal is to determine the real efficacy of this combination in patients who relapsed on previous platinum-based chemotherapy. The goal of this trial is to [conduct], in parallel, a biomarker analysis looking for biomarkers of response [and identify] certain subtypes of SCLC that are better able to respond to the combination of chemotherapy plus pembrolizumab.


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):8581-8581. doi:0.1200/JCO.2022.40.16_suppl.8581

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