- U.S. Food and Drug Administration (FDA) (https://voice.ons.org/topic/us-food-and-drug-administration-fda)
- Oncology drug research (https://voice.ons.org/topic/oncology-drug-research)
- Lung Cancer (https://voice.ons.org/topic/lung-cancer)
- Clinical practice (https://voice.ons.org/topic/clinical-practice)
FDA Approves Nivolumab Plus Ipilimumab for First-Line Metastatic Non-Small Cell Lung Cancer
On May 15, 2020, the U.S. Food and Drug Administration (FDA) approved the combination (https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-nivolumab-plus-ipilimumab-first-line-mnsclc-pd-l1-tumor-expression-1) 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 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 (https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/125554s080lbl.pdf).
View full prescribing information for ipilimumab (https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/125377s109lbl.pdf).
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 (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-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 (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.
For assistance with single-patient oncology investigational new drug applications, contact OCE’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).