In an August press release, Regeneron Pharmaceuticals and Sanofi announced that the phase lll trial of the programmed death (PD-1) inhibitor cemiplimab (marketed as Libtayo) in combination with platinum-doublet chemotherapy was halted early after meeting its overall survival (OS) primary endpoint in patients with advanced nonÐsmall cell lung cancer (NSCLC). Cemiplimab is classified as a fully human monoclonal antibody targeting the immune checkpoint receptor PD-1 on T cells. By binding to PD-1, the agent has been demonstrated to block cancer cells from using the PD-1 pathway to suppress T-cell activation.
The release also noted that the addition of cemiplimab to chemotherapy significantly enhanced OS compared with chemotherapy alone in the trial, which enrolled patients with metastatic or locally advanced disease and tumors with either squamous or nonsquamous histology and across all PD-L1 expression levels. These data are planned to form the basis of regulatory submissions in the United States and the European Union.
The randomized, multicenter, phase lll trial—MPOWER-Lung 3—investigated a first-line combination treatment of cemiplimab and platinum-doublet chemotherapy versus platinum-doublet chemotherapy alone in squamous or nonsquamous advanced NSCLC irrespective of PD-L1 expression. The trial included 466 patients who tested negative for anaplastic lymphoma kinase, epidermal growth factor receptor, and reactive oxygen species mutations and had either previously untreated metastatic NSCLC (stage IV) or locally advanced NSCLC (stage IIIB/C) and were not candidates for definitive chemoradiation.
Patients were randomized 2:1 to receive cemiplimab 350 mg (n = 312) or placebo (n = 154) administered IV every 3 weeks for 108 weeks plus platinum-doublet chemotherapy administered every 3 weeks for four cycles. The coprimary endpoints were OS and progression-free survival, and key secondary endpoints included objective response rate and best overall response. Among trial patients, 30% (n = 139) had tumors with <1% PD-L1 expression, 38% (n = 175) had tumors with 1% to 49% PD-L1 expression, and 33% (n = 152) had tumors with >50% PD-L1 expression. The most common adverse effects reported were musculoskeletal pain, fatigue, rash, and diarrhea. The most common grade 3-4 laboratory abnormalities (>2%) were lymphopenia, hyponatremia, hypophosphatemia, increased aspartate aminotransferase, anemia, and hyperkalemia.
The decision to halt the trial early was based on a recommendation by the Independent Data Monitoring Committee (IDMC) during a protocol-specified interim analysis. In this top-line initial analysis of 466 patients, combining cemiplimab with chemotherapy decreased the risk of death by 29% compared with chemotherapy alone (hazard ratio, 0.71; 95% CI, 0.53-0.93; P = .014). Average OS was 22 months (95% CI, 16 months to not evaluable) for cemiplimab and chemotherapy and 13 months (95% CI, 12-16 months) for chemotherapy alone. No new cemiplimab safety signals were identified in the IDMC analysis, and additional detailed efficacy and safety data will be presented at an upcoming medical meeting. The use of cemiplimab in combination with chemotherapy for advanced NSCLC is currently under clinical investigation, and its safety and efficacy have not been fully evaluated by any regulatory authority.
Dr. Miranda Gogishvili, an oncologist at the High Technology Medical Center, University Clinic, in Tbilisi, Georgia, and a trial investigator, stated, "Cemiplimab in combination with chemotherapy increased median overall survival to 22 months in patients with advanced non-small cell lung cancer, compared to 13 months with chemotherapy alone. Notably, the phase lll trial enrolled patients with a variety of challenging-to-treat disease characteristics, as well as those with locally advanced disease. These data add to the growing body of evidence supporting cemiplimab in advanced non-small cell lung cancer, which also include the pivotal results for cemiplimab monotherapy in cases of high PD-L1 expression."
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