FDA Expands Approval for Companion Diagnostic for Cemiplimab in NSCLC

The FDA has approved the VENTANA PD-L1 (SP263) assay for expanded use in patients with advanced non–small cell lung cancer (NSCLC) to help identify patients who may be candidates for treatment with cemiplimab-rwlc (Libtayo).¹

In February 2021, the regulatory agency approved the PD-1 inhibitor as monotherapy for use in the frontline treatment of patients with advanced NSCLC with a PD-L1 expression level of 50% or higher.²

The approval of cemiplimab was based on data from the phase 3 EMPOWER-Lung 1 trial (NCT033088540), which showed that the agent produced a median overall survival (OS) of 22.1 months (95% CI, 17.7–not estimable [NE]) compared with 14.3 months (95% CI, 11.7-19.2) for chemotherapy, reducing the risk of death by 32% in the intent-to-treat (ITT) population (n = 710; HR, 0.68; 95% CI, 0.53-0.87; P = .0022).²

Additionally, patients treated with cemiplimab experienced a median progression-free survival (PFS) of 6.2 months (95% CI, 4.5-8.3) compared with 5.6 months (95% CI, 4.5-6.1) for those treated with chemotherapy (HR, 0.59; 95% CI, 0.49-0.72; P < .0001).

“Diagnostics, like our high medical value PD-L1 assay portfolio, enable personalized medicine to help improve patient outcomes,” Jill German, head of Pathology Lab at Roche Diagnostics, stated in a news release.¹ “This approval helps physicians make more confident treatment decisions by identifying patients with tumors that may respond to the immunotherapy [cemiplimab].”

The VENTANA PD-L1 assay previously received FDA approval as a companion diagnostic for identifying which adult patients with stage II to IIIA NSCLC whose tumors have PD-L1 expression on 1% or more of tumor cells are eligible to receive adjuvant atezolizumab (Tecentriq) following surgery and platinum-based chemotherapy.⁴

EMPOWER-Lung 1 was a multicenter, open-label, global, phase 3 trial evaluating cemiplimab monotherapy vs investigator’s choice of platinum-doublet chemotherapy in the frontline treatment of patients with advanced NSCLC with a PD-L1 expression of 50% or higher.³

The trial enrolled patients at least 18 years of age with histologically or cytologically confirmed stage IIIB/C or IV squamous or nonsquamous NSCLC with PD-L1 expression of at least 50%, and an ECOG performance status of 0 to 1. Patients who never smoked were excluded from the study.

Patients were randomly assigned 1:1 to receive 350 mg of intravenous cemiplimab every 3 weeks or investigator’s choice of platinum-based chemotherapy. Patients in the chemotherapy arm were permitted to cross over to the cemiplimab arm following disease progression.

OS and PFS served as the co-primary end points. Secondary end points included objective response rate (ORR), duration of response, health-related quality of life, and safety.

Additional data showed cemiplimab elicited an ORR of 37% (95% CI, 32%-42%) compared with 21% (95% CI, 17%-25%) for chemotherapy.²

Results from an additional prespecified analysis conducted in 563 patients with proven PD-L1 expression of at least 50% showed that cemiplimab reduced the risk of death by 43% versus chemotherapy.³ Patients in the cemiplimab arm (n = 283) experienced a median OS that had not yet been reached (NR; 95% CI, 17.9-NE) vs 14.2 months (95% CI, 11.2-17.5) for those in the chemotherapy arm (n = 280; HR, 0.57; 95% CI, 0.42-0.77; P = .0002).

Moreover, the median PFS was 8.2 months (95% CI, 6.1-8.8) and 5.7 months (95% CI, 4.5-6.2) for patients with a PD-L1 expression of at least 50% in the cemiplimab and chemotherapy arms, respectively (HR, 0.54; 95% CI, 0.43-0.68; P < .0001).

Regarding safety, the most common adverse effects reported in more than 10% of the ITT population treated with cemiplimab included musculoskeletal pain, rash, anemia, fatigue, decreased appetite, pneumonia, and cough.²

Previously, in February 2021, the FDA also approved the PD-L1 IHC 22C3 pharmDx assay to help identify patients who may be candidates for treatment with cemiplimab.⁵

References

1. Roche receives FDA approval of label expansion for VENTANA PD- L1 (SP263) assay to identify patients with locally advanced and metastatic non-small cell lung cancer eligible for Libtayo. News release. Roche. March 6, 2023. Accessed March 7, 2023. https://diagnostics.roche.com/global/en/news-listing/
2. FDA approves cemiplimab-rwlc for non-small cell lung cancer with high PD-L1 expression. News release. FDA. February 22, 2021. Accessed March 7, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/
3. Sezer A, Kilickap S, Gümüs M, et al. Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Lancet. 2021;397(10274):592-604. doi:10.1016/S0140-6736(21)00228-2
4. Roche’s VENTANA PD-L1 (SP263) assay receives FDA approval as a companion diagnostic to identify certain non-small cell lung cancer patients eligible for Tecentriq (atezolizumab). News release. Roche. October 22, 2021. Accessed March 7, 2023. https://www.roche.com/media/releases/
5. Agilent PD-L1 IHC 22C3 pharmDx receives expanded FDA approval in non-small cell lung cancer (NSCLC). News release. Agilent Technologies Inc. February 22, 2021. Accessed March 7, 2023. https://www.agilent.com/about/newsroom/