FDA approves nivolumab plus ipilimumab for first-line mNSCLC (PD-L1 tumor expression ≥1%)
On May 15, 2020, the Food and Drug Administration approved the combination of nivolumab (OPDIVO, Bristol-Myers Squibb Co.) plus ipilimumab (YERVOY, Bristol-Myers Squibb Co.) as first-line treatment for patients with metastatic non-small cell lung cancer 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.
Today, the FDA also approved the PD-L1 IHC 28-8 pharmDx (Agilent Technologies, Inc.) as a companion diagnostic device for selecting patients with NSCLC for treatment with nivolumab plus ipilimumab.
Efficacy was investigated in CHECKMATE-227 (NCT02477826), a randomized, open-label, multi-part trial in patients with metastatic or recurrent NSCLC and no prior anticancer therapy. In Part 1a of the trial, 793 patients with PD-L1 tumor expression ≥1% were randomized to receive either the combination of nivolumab plus with 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) (HR 0.79; 95% CI: 0.67, 0.94; p=0.0066).
Median progression-free survival (PFS) per 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 in ≥20% of patients receiving the combination of nivolumab plus ipilimumab in CHECKMATE-227 were fatigue, rash, decreased appetite, musculoskeletal pain, diarrhea/colitis, dyspnea, cough, pruritis, nausea, and hepatitis.
The recommended doses for metastatic NSCLC are nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.
View full prescribing information for OPDIVO.
View full prescribing information for YERVOY.
This application was granted priority review. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
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For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.
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- FDA: Coronavirus Disease 2019 (COVID-19)
- NCI: Coronavirus: What People With Cancer Should Know
- CDC: Coronavirus (COVID-19)
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