Cemiplimab/Chemo Combo Significantly Improves OS Over Chemo Alone in Frontline Advanced NSCLC

The combination of cemiplimab-rwlc (Libtayo) plus platinum-doublet chemotherapy was found to significantly improve overall survival (OS) over chemotherapy alone in the frontline treatment of patients with advanced non–small cell lung cancer (NSCLC), meeting the primary end point of the phase 3 EMPOWER-Lung 3 trial (NCT03409614).¹

The addition of the PD-1 inhibitor to chemotherapy resulted in a 29% reduction in the risk of death in this patient population (HR, 0.71; 95% CI, 0.53-0.93; P = .014). The median OS in the investigative arm was 22.0 months (95% CI, 16–not evaluable [NE]) vs 13.0 months (95% CI, 12-16) in the control arm.

Based on a recommendation issued by the independent data monitoring committee (IDMC) during a protocol-specified interim analysis, the trial has been stopped early. No new safety signals were observed with cemiplimab in the IDMC analysis.

Additional safety and efficacy findings will be presented at an upcoming medical conference. Regeneron Pharmaceuticals, Inc. and Sanofi also shared that the data are planned to form the basis of regulatory submissions in both the United States and the European Union.

“Notably, the phase 3 trial enrolled patients with a variety of challenging-to-treat disease characteristics, as well as those with locally advanced disease,” Miranda Gogishvili, MD, an oncologist at the High Technology Medical Center, University Clinic, stated in a press release. “These data add to the growing body of evidence supporting [cemiplimab] in advanced NSCLC, which also include the pivotal results for [cemiplimab] monotherapy in cases of high PD-L1 expression.”

In the multicenter, phase 3 trial, investigators enrolled a total of 466 patients with squamous or nonsquamous advanced NSCLC, irrespective of PD-L1 expression. Participants had to test negative for ALK, EGFR, and ROS1 mutations, have either previously untreated metastatic stage IV disease or locally advanced stage IIIB or C disease, and could not be eligible for definitive chemoradiation.

Patients enrolled to the trial were randomized 2:1 to receive either cemiplimab at a dose of 350 mg (n = 312) or placebo (n = 154), which was delivered intravenously every 3 weeks for a duration of 108 weeks. Patients also received platinum-doublet chemotherapy, which was administered every 3 weeks for 4 cycles.

The co-primary end points of the trial were OS and progression-free survival, and important secondary end points comprised objective response rate (ORR) and best overall response.

Thirty percent of patients (n = 139) had tumors that had a PD-L1 expression of less than 1%, 38% (n = 175) had tumors with a PD-L1 expression ranging between 1% and 49%, and 33% (n = 152) had tumors with a PD-L1 expression of 50% or higher.

Cemiplimab is currently under investigation as a potential option for patients with advanced cervical cancer.² Results from a recent phase 3 trial presented during the ESMO Virtual Plenary showed that the immunotherapy resulted in a 31% reduction in the risk of death vs chemotherapy in patients with metastatic cervical cancer who had progressed on chemotherapy.

In the overall patient population, those who received cemiplimab (n = 304) experienced a significant improvement in OS vs those who were given chemotherapy (HR, 0.69; 95% CI, 0.56-0.84; P = .00011). The PD-1 inhibitor also resulted in a 25% reduction in the risk of disease progression or death vs chemotherapy (HR, 0.75; 95% CI, 0.63-0.89; P = .00048).

The ORRs in the investigative and control arms were 16% (n = 50) and 6% (n = 19), respectively (95% CI, 13%-21%; P = .00004). The median duration of response with cemiplimab, per Kaplan-Meier estimates, was 16.0 months (95% CI, 12–NE) compared with 7.0 months (95% CI, 5-8) with chemotherapy.

Other trials that are examining its use in combination with conventional or novel therapeutic strategies in patients with solid tumors and blood cancers.

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, Inc. and Sanofi. August 5, 2021. Accessed August 5, 2021. https://bit.ly/3xseTyW
2. Positive phase 3 Libtayo (cemiplimab) results in advanced cervical cancer presented at ESMO Virtual Plenary. News release. Sanofi. May 12, 2021. Accessed August 5, 2021. https://bit.ly/3fe9cxm