Early results from the phase 1/2 LUPER study indicated that lurbinectedin in combination with pembrolizumab demonstrated no unexpected toxicity and promising preliminary second-line efficacy for patients with relapsed small cell lung cancer, according to Antonio Calles, MD .
Preliminary findings indicated that second-line treatment with lurbinectedin (Zepzelca) and pembrolizumab (Keytruda) after progression from platinum-based chemotherapy produced manageable safety and potential efficacy in relapsed small cell lung cancer (SCLC), according to with Antonio Calles, MD.
The combination was evaluated as part of the phase 1/2 LUPER study (NCT04358237), preliminary results of which were presented at 2022 American Society of Clinical Oncology (ASCO)🇧🇷 The 13 patient population 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. Seventy-five percent of patients responded at 9 months.
The recommended phase 2 dose was 3.2 mg/mtwo of lurbinectedin and 200 mg of pembrolizumab intravenously once every 3 weeks. While the research is still in its early stages, Calles detailed how this could impact the future treatment landscape and address unmet needs.
“I expect the SCLC treatment landscape to evolve rapidly,” he said. 🇧🇷[Currently,] the standard of care is chemoimmunotherapy in the first-line setting. This trial was designed prior to the approval of any of these [therapies.] There is still room for chemotherapy/immunotherapy treatment in the second-line setting, such as patients with locally advanced disease who relapse or patients who for whatever 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 be a potential option in the future to treat these patients.”
In a discussion with CancerNetwork🇧🇷Calles, an oncologist at the Department of Medical Oncology at Hospital General Universitario Gregorio Marañón, highlighted the preliminary safety associated with the combination regimen and unmet needs in patients with advanced disease after treatment with platinum-based chemotherapy.
Cancer Network🇧🇷: Could you tell me about the rationale for evaluating lurbinectedin and pembrolizumab in small cell lung cancer relapse?
streets: Lurbinectedin is a new agent that acts on the transactivation [transcript] factors and also modulates the tumor microenvironment. It is currently FDA-approved for the treatment of patients with relapse during or after platinum-based chemotherapy. This is a phase 1/2 study evaluating the safety and preliminary efficacy of combining pembrolizumab, an anti-PD1 agent, with lurbinectedin.
What were the key security findings read at this year’s meeting?
We were able to find the maximum tolerated dose. We also found that we can use full doses of 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 events [effects is consistent] with what is known for this agent in this scenario. And for lurbinectedin, the main toxicity was neutropenia and fatigue, which was also in the known range for single-agent lurbinectedin. There was no unexpected toxicity with the combination.
Where do you see research efforts being focused from here?
Our main objective is to determine the actual effectiveness of this combination in patients who relapsed on previous platinum-based chemotherapy. The aim of this test is [conduct]in parallel, an analysis of biomarkers in search of response biomarkers [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, and others. A phase 1/2 study of lurbinectedin (L) in combination with pembrolizumab (P) in relapsed small cell lung cancer (SCLC): the LUPER trial. J Clin Oncol. 2022;40(suppl 16):8581-8581. doi:0.1200/JCO.2022.40.16_suppl.8581