On May 26, 2020, the U.S. Food and Drug Administration (FDA) approved the combination of nivolumab (Opdivo®) plus ipilimumab (Yervoy®) and two cycles of platinum-doublet chemotherapy as first-line treatment for patients with metastatic or recurrent non-small cell lung cancer (NSCLC) with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.
Efficacy was investigated in a randomized, open-label trial (CHECKMATE-9LA; NCT03215706) of patients with metastatic or recurrent NSCLC. Patients were randomized to receive either the combination of nivolumab plus ipilimumab and two cycles of platinum-doublet chemotherapy (n = 361) or platinum-doublet chemotherapy for four cycles (n = 358).
The trial demonstrated a statistically significant benefit in overall survival (OS) for patients treated with nivolumab plus ipilimumab and chemotherapy compared to those who received chemotherapy. Median OS was 14.1 months (95% CI = 13.2, 16.2) versus 10.7 months (95% CI = 9.5, 12.5), respectively (HR = 0.69; 96.71% CI = 0.55, 0.87).
Median progression-free survival per blinded independent central review (BICR) was 6.8 months (95% CI = 5.6, 7.7) in the nivolumab plus ipilimumab and chemotherapy arm and five months (95% CI = 4.3, 5.6) in the chemotherapy arm (HR = 0.70; 95% CI = 0.57, 0.86). Confirmed overall response rate per BICR was 38% (95% CI = 33, 43) and 25% (95% CI = 21, 30) respectively. Median response duration was 10 months in the nivolumab plus ipilimumab and chemotherapy arm and 5.1 months in the chemotherapy arm.
The most common adverse reactions (≥ 20%) were fatigue, musculoskeletal pain, nausea, diarrhea, rash, decreased appetite, constipation, and pruritus.
The recommended nivolumab dose for this indication is 360 mg every three weeks with ipilimumab 1 mg/kg every six weeks and two cycles of platinum-doublet chemotherapy. The nivolumab and ipilimumab is continued 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 collaborated with Australia’s Therapeutic Goods Administration (TGA), Health Canada, and Singapore’s Health Sciences Authority (HSA) on the review of the application as part of Project Orbis. FDA approved the application two months ahead of schedule. FDA’s and HSA’s decisions were near simultaneous, whereas the application review is ongoing for TGA and Health Canada.
The review used the Real-Time Oncology Review, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment.
FDA granted the application priority review and fast track designation. 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.