Nivolumab (Opdivo)

General information

Class/mechanism: PD-1 receptor antibody. Nivolumab is an IgG4 kappa human monoclonal antibody which binds to the PD-1 (programmed death receptor-1) receptor and blocks its interaction with the ligands PD-L1 and PD-L2. Normally, PD-L1 and PD-L2 binding to the PD-1 receptor on T cells inhibits T-cell proliferation and cytokine production, which can impede immune system surveillance of tumors. By interfering with the binding of PD-L1 and PD-L2 to the PD-1 receptor, nivolumab can cause upregulation of the anti-tumor immune response.
Route: IV
Extravasation: no information

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.

Diseases for which it is used

• Bladder cancer
• Esophageal cancer
• Gastric cancer
• Head and neck cancer
• Hepatocellular carcinoma
• Hodgkin lymphoma
• Melanoma
• Mesothelioma
• Non-small cell lung cancer
• Renal cell carcinoma

Diseases for which it was used

• Small cell lung cancer

Patient drug information

• Nivolumab (Opdivo) package insert
• Nivolumab (Opdivo) patient drug information (Chemocare)
• Nivolumab (Opdivo) patient drug information (UpToDate)

History of changes in FDA indication

Bladder cancer

• 2/2/2017: Granted FDA accelerated approval for treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with a platinum-containing chemotherapy.

Colorectal cancer

• 8/1/2017: Granted FDA accelerated approval for the treatment of patients 12 years and older with mismatch repair deficient (dMMR) and microsatellite instability high (MSI-H) metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.

Esophageal cancer

• 6/10/2020: for patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy. (New disease entity)

Head and neck cancer

• 11/10/2016: FDA approved for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after a platinum-based therapy.

Hepatocellular carcinoma

• 9/22/2017: Granted FDA accelerated approval for the treatment of hepatocellular carcinoma (HCC) in patients who have been previously treated with sorafenib. (New disease entity)
• 3/10/2020: Approved in combination with ipilimumab for patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. (Approval extended to combination therapy)

Hodgkin lymphoma

• 5/17/2016: FDA approval expanded for the treatment of patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin (Adcetris).

Melanoma

• 12/22/2014: FDA approved for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab
  • If BRAF V600 mutation positive, a BRAF inhibitor.
• 9/30/2015: Granted FDA accelerated approval in combination with ipilimumab for the treatment of patients with BRAF V600 wild-type, unresectable or metastatic melanoma.
• 9/13/2016: FDA dosing recommendation changed to 240 mg IV every two weeks until disease progression or intolerable toxicity for renal cell carcinoma, metastatic melanoma, and non-small cell lung cancer. When combined with ipilimumab for melanoma, after completion of ipilimumab, the recommended nivolumab dose will be 240 mg every two weeks until disease progression or intolerable toxicity.
• 12/20/2017: Granted FDA regular approval for the adjuvant treatment of patients with melanoma with involvement of lymph nodes or in patients with metastatic disease who have undergone complete resection.

Mesothelioma

• 10/2/2020: Approved in combination with ipilimumab as first-line treatment for adult patients with unresectable malignant pleural mesothelioma. (New disease entity)

Non-small cell lung cancer

• 3/4/2015: Approved for the treatment of patients with metastatic squamous non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy.
• 10/9/2015: Approval expanded for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. (Histology indication expanded)
  • Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving Opdivo.
• 9/13/2016: FDA dosing recommendation changed to 240 mg IV every two weeks until disease progression or intolerable toxicity for renal cell carcinoma, metastatic melanoma, and non-small cell lung cancer. When combined with ipilimumab for melanoma, after completion of ipilimumab, the recommended nivolumab dose will be 240 mg every two weeks until disease progression or intolerable toxicity.
• 5/15/2020: Approved in combination with ipilimumab 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. (Expanded to first-line setting, with PD-L1 expression requirement)
• 5/26/2020: Approved in combination with ipilimumab and 2 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. (PD-L1 expression requirement removed when given with chemotherapy)

Renal cell carcinoma

• 11/23/2015: FDA approval expanded for the treatment of advanced renal cell carcinoma in patients who have received prior anti-angiogenic therapy.
• 9/13/2016: FDA dosing recommendation changed to 240 mg IV every two weeks until disease progression or intolerable toxicity for renal cell carcinoma, metastatic melanoma, and non-small cell lung cancer. When combined with ipilimumab for melanoma, after completion of ipilimumab, the recommended nivolumab dose will be 240 mg every two weeks until disease progression or intolerable toxicity.
• 4/16/2018: FDA approved to be used in combination with Ipilimumab (Yervoy) for the treatment of intermediate or poor risk, previously untreated advanced renal cell carcinoma.
• 1/22/2021: Approved to be used in combination with Cabozantinib (Cabometyx) as first-line treatment for patients with advanced renal cell carcinoma (RCC).

Withdrawn indications

Small cell lung cancer

• 8/16/2018: Granted FDA accelerated approval for patients with metastatic small cell lung cancer (SCLC) with progression after platinum-based chemotherapy and at least one other line of therapy.
• 12/29/2020: Indication withdrawn by the manufacturer.

Also known as

• Code names: BMS-936558, MDX-1106, ONO-4538
• Brand name: Opdivo