Phase 3 Clinical Trial of First-Line Cemiplimab Combo in NSCLC Stopped Early Due to Significantly Improved Survival

First-line cemiplimab-rwlc (Libtayo) plus platinum chemotherapy elicited significantly improved overall survival (OS) results vs chemotherapy alone in a population of patients with advanced or metastatic non–small cell lung cancer (NSCLC), according to a press release from drug developer Regeneron Pharmaceuticals who reported on the results of the phase 3 EMPOWER-Lung 3 trial (NCT03409614).¹

The trial was stopped early due to a highly significant survival improvement noted at the protocol-specified interim analysis. This decision was based on a recommendation from an independent data monitoring committee which found that patients treated with the combination experienced a reduction in risk of death by 29% vs chemotherapy alone (HR, 0.71; 95% CI, 0.53-0.93; P = .014). The median OS was 22 months (95% CI, 16–not evaluable) with the combination regimen compared with 13 months in the chemotherapy-alone arm (95% CI, 12-16).

“Libtayo 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,” trial investigator Miranda Gogishvili, MD, an oncologist at the High Technology Medical Center, University Clinic, Tbilisi, Georgia, said in a press release. “Notably, the phase 3 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 Libtayo in advanced non–small cell lung cancer, which also include the pivotal results for Libtayo monotherapy in cases of high PD-L1 expression.”

The randomized, multicenter trial clinical trial examined the efficacy of frontline cemiplimab in combination with platinum-doublet chemotherapy in a population of patients with squamous or nonsquamous disease regardless of PD-L1 status. Patients who enrolled tested negative for ALK, EGFR, and ROS1 mutations, had previously untreated metastatic stage IV NSCLC or locally advanced stage IIIB/C NSCLC, and were not eligible for definitive chemotherapy.

Patients were randomized 2:1 and were given either 350 mg of cemiplimab (n = 312) or placebo (n = 154), which was administered intravenously every 3 weeks over the course of 108 weeks. Moreover, platinum-doublet chemotherapy was administered every 3 weeks for 4 cycles.

The co-primary end points of the study were OS and progression-free survival (PFS), with key secondary end points including objective response rate and best overall response.

In total, 30% of patients (n = 139) had PD-L1 expression of less than 1%, 38% (n = 175) had tumors with expression of 1% to 49%, and 33% had expression of 50% or more.

Cemiplimab was approved by the FDA in February 2021 for the treatment of patients with advanced NSCLC whose PD-L1 expression is 50% or greater.2 The approval was based on the results of the phase 3 EMPOWER-Lung 1 trial (NCT03088540), which indicated that patients who were treated with the agent after a median follow up of 13.1 months experienced a median OS of 22.1 months vs 14.3 months among those who received chemotherapy alone (HR, 0.68; 95% CI, 0.53-0.87; P = .0022). Additionally, the median PFS in both respective cohorts was 6.2 months and 5.6 months (HR, 0.59; 95% CI, 0.49-0.72; P <.0001).

Notably, the combination of cemiplimab and chemotherapy are still under investigation for the treatment of patients with advanced NSCLC and its safety and efficacy have yet to be full evaluated by a regulatory organization.

References

1. Phase 3 trial of Libtayo (cemiplimab-rwlc) combined with chemotherapy stopped early due to significant improvement in overall survival in patients with first-line advanced non-small cell lung cancer. News release. Regeneron Pharmaceuticals. August 5, 2021. Accessed August 5, 2021. https://bit.ly/3ymiVKp
2. FDA approves Libtayo (cemiplimab-rwlc) monotherapy for patients with first-line advanced non-small cell lung cancer with PD-L1 expression of ≥50%. News release. Regeneron Pharmaceuticals, Inc. February 22, 2021. Accessed August 5, 2021. https://bit.ly/3ipNvgD