"This is the largest clinical trial evaluating a PD-1 inhibitor as a first-line monotherapy in patients with advanced non–small cell lung cancer with high PD-L1 expression. These positive results are extremely encouraging."
A phase III clinical trial of cemiplimab (Libtayo), a PD-1 inhibitor, for the treatment of patients with treatment-naïve, locally advanced or metastatic non–small cell lung cancer (NSCLC) who tested positive for PD-L1 in ≥50% of their tumor cells has been stopped early after achieving the primary end point of the study with significant improvement in overall survival (OS) compared with a platinum-doublet chemotherapy regimen, announced Regeneron Pharmaceuticals in a press release.
Following recommendations from an Independent Data Monitoring Committee that the trial be stopped early, investigators will modify the trial to allow all patients to receive the study drug for investigational use. Data from this trial will form the basis of regulatory submissions in 2020 in both the United States and European Union. Detailed findings from these data will be presented at an upcoming medical meeting.
"This is the largest clinical trial evaluating a PD-1 inhibitor as a first-line monotherapy in patients with advanced non–small cell lung cancer with high PD-L1 expression. These positive results are extremely encouraging, and we look forward to advancing a potential new treatment option for these patients," said John Reed, MD, PhD, global head of research and development at Sanofi, in a statement.
Cemiplimab as monotherapy reduced the risk of death by 32.4% compared with the control regimen (HR, 0.676; 95% CI, 0.525-0.870; P = .002), despite one-third of patients entering the trial within the past 6 months and all patients being able to crossover from the chemotherapy arm in the case of disease progression. No new safety signals for cemiplimab were identified.
The open-label, multicenter clinical trial (NCT03088540) randomized 712 patients 1:1 to receive either cemiplimab at 350 mg every 3 weeks for up to 108 weeks or an investigator-selected platinum-doublet chemotherapy regimen for 4 to 6 cycles with or without pemetrexed as maintenance therapy. A co-primary end point of the trial is progression-free survival, and the secondary end points include overall response rate, duration of response, safety, and quality of life.
The trial included patients with locally advanced NSCLC of either stage IIIB or IIIC who were not eligible for surgery or definitive chemoradiation, had progressed after definitive chemoradiation, or who were previously untreated for metastatic NSCLC. Patients were able to enroll to the trial if they had controlled hepatitis B, hepatitis C, or HIV or had pre-treated and stable brain metastases. Patients could change to the investigational therapy if their disease had progressed on trial.
"While demonstrating a survival benefit in first-line NSCLC has been challenging for immunotherapies, the one FDA-approved anti–PD-1 monotherapy has changed the therapeutic paradigm," commented George D. Yancopoulos, MD, PhD, co-founder, president and chief scientific officer of Regeneron, in a statement. "We are pleased with the results of this trial that demonstrate the survival benefit of Libtayo in these patients and hope it may become a potential alternative for physicians and patients."
An additional phase III clinical trial is expected to complete enrollment in 2020 for analysis of cemiplimab in combination with chemotherapy as treatment of patients with advanced NSCLC irrespective of the PD-L1 status. The agent is a fully human monoclonal antibody that targets the immune checkpoint receptor PD-1 on T cells. It has been shown to block cancer cells from using the pathway for suppression of T-cell activation.
Cemiplimab has been approved in the United States, as well as the European Union and other countries, as a treatment of patients with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not eligible for surgery or radiation of curative intent.
The extensive clinical program for this agent aims to evaluate the drug for the treatment of difficult-to-treat cancers. A potentially registrational phase II trial is evaluating cemiplimab in patients with basal cell carcinoma, and additional studies are evaluating the drug in the adjuvant and neoadjuvant space of CSCC.
A phase III registrational study is evaluating cemiplimab in patients with cervical cancer, while other trials are looking to combine the agent with novel therapeutic approaches for solid tumors, as well as hematologic malignancies. The safety and efficacy of these potential uses have not been established by any regulatory authority.
Phase 3 Trial of Libtayo (Cemiplimab) as Monotherapy for First-Line Advanced Non-Small Cell Lung Cancer Stopped Early Due to Highly Significant Improvement in Overall Survival [news release]. Tarrytown, NY: Regeneron Pharmaceuticals, Inc; April 27, 2020. https://bit.ly/3cJt48O. Accessed April 27, 2020.