First Dual Immunotherapy Approval for Lung Cancer: FDA Approves Ipilimumab Plus Nivolumab

On 15 May 2020, the US Food and Drug Administration (FDA) approved a combination for patients with metastatic non-small-cell lung cancer as first-line treatment: nivolumab (Opdivo) plus ipilimumab (Yervoy), two immunotherapies. Patients must not have epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor alterations, and an FDA-approved test must show their tumors have PD-L1 expression ≥ 1%, meaning positive.

At the same time, the FDA also approved PD-L1 IHC 28-8 pharmDx (Agilent Technologies, Inc.) as a diagnostic device to determine PD-L1 levels in patients with non-small-cell lung cancer (NSCLC) for treatment with nivolumab plus ipilimumab.

The Opdivo plus Yervoy combination had previously received FDA approval for melanoma (2015), kidney cancer (2018), and MSI-H/dMMR-positive colorectal cancers (2018).

The CHECKMATE-227 Trial

The efficacy of this dual immunotherapy as first-line lung cancer treatment was investigated in patients with metastatic or recurrent NSCLC who had received no previous cancer treatment, in a randomized, open-label, multipart clinical trial called CHECKMATE-227.

Part 1a of the study enrolled 793 patients with PD-L1 expression ≥ 1%, who were randomly assigned to one of two arms:

• 396 patients received nivolumab plus ipilimumab
• 397 patients received platinum-based doublet chemotherapy

Results

• In PD-L1-positive patients, the study showed that, compared with platinum-based doublet chemotherapy, nivolumab plus ipilimumab immunotherapy produced a statistically significant improvement in overall survival.
• Median overall survival was 17.9 months in the immunotherapy arm and 14.1 months in the chemotherapy arm.
• Starting treatment with dual immunotherapy was found to reduce the risk of death by 21%.

Median progression-free survival, measured by blinded independent central review, was 5.1 months in the nivolumab plus ipilimumab arm and 5.6 months in the platinum-based doublet chemotherapy arm (HR 0.82; 95% CI: 0.69, 0.97). The confirmed overall response rate was 36% in the immunotherapy arm and 30% in the chemotherapy arm. Median response duration was 23.2 months with nivolumab plus ipilimumab and 6.2 months with platinum-based doublet chemotherapy.

In CHECKMATE-227, ≥ 20% of patients receiving nivolumab plus ipilimumab experienced the following common adverse effects: fatigue, rash, decreased appetite, musculoskeletal pain, diarrhea/colitis, shortness of breath, cough, itching, nausea and hepatitis (see immunotherapy adverse effects).

The recommended doses for metastatic non-small-cell lung cancer are nivolumab 3 mg/kg every 3 weeks and ipilimumab 1 mg/kg every 6 weeks, for up to 2 years in patients without unacceptable adverse effects or disease progression. 

Manage preferences to view external content

Manage preferences to view external content