Antonio Calles, MD highlights the promising preliminary activity of lurbinectedin and pembrolizumab in relapsed SCLC

According to Antonio Calles, MD, initial results from the Phase 1/2 LUPER trial showed that lurbinectedin in combination with pembrolizumab had no unexpected toxicities and promising preliminary efficacy in second-line patients with relapsed small cell lung cancer.

Preliminary results indicated that second-line treatment with lurbinectedin (Zepzelca) and pembrolizumab (Keytruda) provided controllable safety and potential efficacy in relapsed small cell lung cancer (SCLC) after progression to platinum-based chemotherapy, according to Antonio Calles, MD.

The combination was evaluated in the phase 1/2 LUPER study (NCT04358237), the preliminary results of which were presented at the 2022 American Society for Clinical Oncology (ASCO). The population of 13 patients was treated for a median of 3.1 months at 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. 75% of patients were responders at 9 months.

The recommended phase 2 dose was 3.2 mg/m22 lurbinectedin and 200 mg intravenous pembrolizumab once every 3 weeks. Although the research is still in its early stages, Calles outlined how it could impact the treatment landscape and fill unmet needs in the future.

“Hopefully, the treatment landscape of SCLC will evolve rapidly,” he said. “[Currently,] Standard therapy is chemoimmunotherapy in first-line therapy. This study was developed prior to the approval of any of these studies [therapies.] There is still room for chemotherapy/immunotherapy treatment in the second-line setting, such as B. Patients with locally advanced disease who are relapsing or who for some reason were not treated with chemotherapy/immunotherapy in the first-line setting. Again, we do not know how to treat patients after failure of first-line chemotherapy/immunotherapy. This combination could represent a potential option to treat these patients in the future.”

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

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

Calls: Lurbinectedin is a new drug that acts on transactivation [transcript] Factors and also modulates the tumor microenvironment. It is currently FDA approved for the treatment of patients who relapse during or after platinum-based chemotherapy. This is a phase 1/2 study evaluating the safety and preliminary efficacy of the combination of pembrolizumab, an anti-PD1 drug, with lurbinectedin.

What were the key security takeaways read at this year’s meeting?

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

Where do you see research efforts from here?

Our main goal is to determine the true efficacy of this combination in patients who have relapsed from previous platinum-based chemotherapy. The aim of this study is [conduct]parallel a biomarker analysis looking for biomarkers of the reaction [and identify] certain subtypes of SCLC that respond better to the combination of chemotherapy and pembrolizumab.


Calles A, Navarro A, Doger B, et al. A phase 1/2 study of lurbinectedin (L) in combination with pembrolizumab (P) in relapsed small cell lung cancer (SCLC): the LUPER study. J Clin Oncol. 2022;40(Supplement 16):8581-8581. doi:0.1200/JCO.2022.40.16_suppl.8581


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