Cemiplimab Improves Survival in Frontline PD-L1–High NSCLC

The PD-1 inhibitor cemiplimab significantly improved overall survival as a frontline treatment for patients with high–PD-L1 non–small cell lung cancer.

The PD-1 inhibitor cemiplimab (Libtayo) significantly improved overall survival (OS) versus platinum-based chemotherapy as a frontline treatment for patients with locally advanced or metastatic non—small cell lung cancer (NSCLC) and a PD-L1 expression level of at least 50%, meeting the primary end point of a phase 3 trial.1

In the study, cemiplimab reduced the risk of death by 32.4% versus chemotherapy (HR, 0.676; 95% CI, 0.525-0.870; P = .002). Based on the findings, an independent monitoring panel has recommended halting the trial early, and all patients on the trial will now be allowed to receive cemiplimab.

Also of note, there were no new safety signals with cemiplimab compared with previous data. Regeneron Pharmaceuticals, Inc, and Sanofi, the codevelopers of cemiplimab, reported in a press release that the full findings will support regulatory submissions in the United States and European Union, and will be shared at an upcoming medical meeting.

"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," George D. Yancopoulos, MD, PhD, co-founder, president and chief scientific officer of Regeneron, said in the press release. "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."

The multicenter, open-label phase 3 trial included 712 patients with locally advanced NSCLC (stage IIIb/c), who were not candidates for surgical resection or definitive chemoradiation or had progressed after treatment with definitive chemoradiation, or previously untreated metastatic NSCLC (stage IV). Patients had PD-L1 expression on at least 50% of their tumor cells. Enrollment was allowed for patients with both squamous and nonsquamous NSCLC.

Patients were randomized in a 1:1 ratio to either cemiplimab (350 mg IV every 3 weeks for up to 108 weeks) or investigators choice of platinum-double chemotherapy for 4 to 6 cycles with or without maintenance pemetrexed (Alimta). At progression, patients were allowed to cross over—those on the control arm could receive cemiplimab, and patients randomized to cemiplimab could combine treatment with the PD-1 inhibitor with 4 to 6 cycles of chemotherapy.

Overall, 710 patents were evaluable for the interim analysis. Beyond the primary OS endpoint, secondary outcome measures included overall response rate (ORR), duration of response, and quality of life.

Cemiplimab is currently approved by the FDA for the treatment of patients with metastatic cutaneous squamous cell carcinoma (CSCC) or patients with locally advanced CSCC who are not candidates for curative surgery or curative radiation.2

The approval was based on a combined analysis of data from the phase 2 EMPOWER-CSCC-1 (Study 1540) trial and 2 advanced CSCC expansion cohorts from a phase 1 trial (Study 1423). The 108-patient combined analysis included 75 patients with metastatic CSCC and 33 patients with locally advanced CSCC.

Across the entire population, the ORR at a median follow-up of 8.9 months was 47% (95% CI, 38-47). The complete response (CR) rate was 4% and the partial response (PR) rate was 44%. The duration of response ranged from 1 month to over 15 months. Sixty-one percent of patients had a duration of response ≥6 months.

Among 75 patients with metastatic CSCC, the ORR was 47% (95% CI, 35-59). The CR rate was 5% and the PR rate was 41%. The duration of response ranged from 3 months to over 15 months. Sixty percent of patients had a duration of response ≥6 months. In the 33 patients with locally advanced disease, the ORR was 49% (95% CI, 31-67), comprising all PRs. The duration of response ranged from 1 month to over 13 months. Sixty-three percent of patients had a duration of response ≥6 months.


  1. 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. Published April 27, 2020. https://bit.ly/2KElhgE. Accessed April 27, 2020.
  2. FDA approves cemiplimab-rwlc for metastatic or locally advanced cutaneous squamous cell carcinoma. Published September 28, 2018. https://bit.ly/2y2DzoX. Accessed April 27, 2020