. 2021 Jun 10;26(9):797–806. doi: 10.1002/onco.13819

Table 1.

Nivolumab background information

Structure	Fully human IgG4 monoclonal antibody.
Mechanism of action	Binds to the PD‐1 cell membrane receptor and blocks the interaction of PD‐1 with its ligands, PD‐L1 and PD‐L2.
Pharmacokinetics	The exposure to nivolumab increases dose proportionally over the dose range of 0.1 to 10 mg/kg administered every 2 weeks. The predicted exposure of nivolumab after a 30‐minute infusion is comparable to that observed with a 60‐minute infusion. Steady‐state concentrations of nivolumab were reached by 12 weeks when administered at 3 mg/kg every 2 weeks, and systemic accumulation was 3.7‐fold. The geometric mean volume of distribution at steady state and coefficient of variation is 6.8 L (27.3%). The geometric mean elimination half‐life is 25 days (77.5%).
Prior approvals (before March 10, 2020)	Melanoma: Patients with unresectable or metastatic melanoma, as a single agent or in combination with ipilimumab. Patients with melanoma with lymph node involvement or metastatic disease who have undergone complete resection, in the adjuvant setting.
Non‐small cell lung cancer: Patients with metastatic NSCLC and progression on or after platinum‐based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA‐approved therapy for these aberrations prior to receiving nivolumab.
Small cell lung cancer: Patients with metastatic SCLC with progression after platinum‐based chemotherapy and at least one other line of therapy. ^a
Renal cell carcinoma: Patients with advanced RCC who have received prior antiangiogenic therapy. Patients with intermediate or poor risk, previously untreated advanced RCC, in combination with ipilimumab.
Classical Hodgkin lymphoma: Adult patients with cHL that has relapsed or progressed after^a autologous HSCT and brentuximab vedotin, or after three or more lines of systemic therapy that includes autologous HSCT.
Squamous cell carcinoma of the head and neck: Patients with recurrent or metastatic SCCHN with disease progression on or after a platinum‐based therapy.
Urothelial carcinoma: Patients with locally advanced or metastatic urothelial carcinoma who^a have disease progression during or following platinum‐containing chemotherapy. Patients with locally advanced or metastatic urothelial carcinoma who^a have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum‐containing chemotherapy.
Colorectal cancer: Adult and pediatric (12 years and older) patients with MSI‐H or dMMR metastatic CRC that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan, as a single agent or in combination with ipilimumab. ^a
Hepatocellular carcinoma: Patients with HCC who have been previously treated with sorafenib.

Structure

Fully human IgG4 monoclonal antibody.

Mechanism of action

Binds to the PD‐1 cell membrane receptor and blocks the interaction of PD‐1 with its ligands, PD‐L1 and PD‐L2.

Pharmacokinetics

The exposure to nivolumab increases dose proportionally over the dose range of 0.1 to 10 mg/kg administered every 2 weeks. The predicted exposure of nivolumab after a 30‐minute infusion is comparable to that observed with a 60‐minute infusion. Steady‐state concentrations of nivolumab were reached by 12 weeks when administered at 3 mg/kg every 2 weeks, and systemic accumulation was 3.7‐fold. The geometric mean volume of distribution at steady state and coefficient of variation is 6.8 L (27.3%). The geometric mean elimination half‐life is 25 days (77.5%).

Prior approvals (before March 10, 2020)

Melanoma:

Patients with unresectable or metastatic melanoma, as a single agent or in combination with ipilimumab.

Patients with melanoma with lymph node involvement or metastatic disease who have undergone complete resection, in the adjuvant setting.

Non‐small cell lung cancer:

Patients with metastatic NSCLC and progression on or after platinum‐based chemotherapy.

Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA‐approved therapy for these aberrations prior to receiving nivolumab.

Small cell lung cancer:

Patients with metastatic SCLC with progression after platinum‐based chemotherapy and at least one other line of therapy.

Renal cell carcinoma:

Patients with advanced RCC who have received prior antiangiogenic therapy.

Patients with intermediate or poor risk, previously untreated advanced RCC, in combination with ipilimumab.

Classical Hodgkin lymphoma:

Adult patients with cHL that has relapsed or progressed after^a autologous HSCT and brentuximab vedotin, or after three or more lines of systemic therapy that includes autologous HSCT.

Squamous cell carcinoma of the head and neck:

Patients with recurrent or metastatic SCCHN with disease progression on or after a platinum‐based therapy.

Urothelial carcinoma:

Patients with locally advanced or metastatic urothelial carcinoma who^a have disease progression during or following platinum‐containing chemotherapy.

Patients with locally advanced or metastatic urothelial carcinoma who^a have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum‐containing chemotherapy.

Colorectal cancer:

Adult and pediatric (12 years and older) patients with MSI‐H or dMMR metastatic CRC that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan, as a single agent or in combination with ipilimumab.

Hepatocellular carcinoma:

Patients with HCC who have been previously treated with sorafenib.

^{^a}

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Abbreviations: ALK, anaplastic lymphoma kinase; cHL, classical Hodgkin lymphoma; CRC, colorectal cancer; dMMR, mismatch repair deficient; EGFR, epidermal growth factor receptor; FDA, U.S. Food and Drug Administration; HCC, hepatocellular carcinoma; HSCT, hematopoietic stem cell transplantation; MSI‐H, microsatellite instability high; NSCLC, non‐small cell lung cancer; PD‐1, programmed death‐1; PD‐L1, programmed death‐ligand 1; PD‐L2, programmed death‐ligand 2; RCC, renal cell carcinoma; SCCHN, squamous cell carcinoma of the head and neck; SCLC, small cell lung cancer.

Source: Nivolumab U.S. Package Insert dated September 18, 2019 (Supplement 75).