On May 15, 2020, the U.S. Food and Drug Administration (FDA) approved the combination of nivolumab (Opdivo®) and ipilimumab (Yervoy®) as first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥ 1%), as determined by an FDA-approved test, with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations. 

FDA Approves Nivolumab Plus Ipilimumab for First-Line Metastatic Non-Small Cell Lung Cancer

FDA also approved the PD-L1 IHC 28-8 pharmDx qualitative assay as a companion diagnostic device for selecting patients with NSCLC for treatment with nivolumab plus ipilimumab. 

Efficacy was investigated in a randomized, open-label, multipart trial (CHECKMATE-227; NCT02477826) of patients with metastatic or recurrent NSCLC and no prior anticancer therapy. Part 1a of the trial randomized 793 patients with PD-L1 tumor expression ≥ 1% to receive either the combination of nivolumab plus ipilimumab (n = 396) or platinum-doublet chemotherapy (n = 397). 

The trial demonstrated a statistically significant improvement in overall survival (OS) for patients with PD-L1 tumor expression ≥ 1% receiving nivolumab plus ipilimumab compared to those treated with platinum-doublet chemotherapy. Median OS was 17.1 months (95% CI = 15, 20.1) versus 14.9 (95% CI = 12.7, 16.7), respectively (HR = 0.79; 95% CI = 0.67, 0.94; p = 0.0066). 

Median progression-free survival (PFS), based on the blinded independent central review (BICR), was 5.1 months (95% CI = 4.1, 6.3) in the nivolumab plus ipilimumab arm and 5.6 months (95% CI = 4.6, 5.8) in the platinum-doublet chemotherapy arm (HR = 0.82; 95% CI = 0.69, 0.97). Confirmed overall response rate (ORR) per BICR was 36% (95% CI = 31, 41) and 30% (95% CI = 26, 35), respectively. Median response duration was 23.2 months in the nivolumab plus ipilimumab arm and 6.2 months in the platinum-doublet chemotherapy arm. 

The most common adverse reactions (≥ 20%) were fatigue, rash, decreased appetite, musculoskeletal pain, diarrhea or colitis, dyspnea, cough, pruritis, nausea, and hepatitis. 

The recommended doses for metastatic NSCLC are nivolumab 3 mg/kg every two weeks and ipilimumab 1 mg/kg every six weeks until disease progression, unacceptable toxicity, or up to two years in patients without disease progression. 

View full prescribing information for nivolumab

View full prescribing information for ipilimumab

FDA granted the application priority review. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088. 

For assistance with single-patient oncology investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.