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

Table 2.

Ipilimumab background information

Structure	Recombinant human IgG1 kappa monoclonal antibody.
Mechanism of action	Binds to the CTLA‐4 cell membrane receptor and blocks the interaction of CTLA‐4 with its ligands, CD80 and CD86.
Pharmacokinetics	The pharmacokinetics of ipilimumab is linear in the dose range of 0.3 mg/kg to 10 mg/kg. Following administration of ipilimumab every 3 weeks, the systemic accumulation was 1.5‐fold or less. Steady‐state concentrations of ipilimumab were reached by the third dose; the mean minimum concentration at steady state was 19.4 mcg/mL at 3 mg/kg and 58.1 mcg/mL at 10 mg/kg every 3 weeks. The mean (percent coefficient of variation) terminal half‐life was 15.4 days (34%) and the mean (percent coefficient of variation) CL was 16.8 mL/h (38%). The CL of ipilimumab was unchanged in presence of anti‐ipilimumab antibodies.
Prior approvals (before March 10, 2020)	Treatment of unresectable or metastatic melanoma in adults and pediatric patients (12 years and older). Adjuvant treatment of patients with cutaneous melanoma with pathologic involvement of regional lymph nodes of more than 1 mm who have undergone complete resection, including total lymphadenectomy. Treatment of patients with intermediate or poor risk, previously untreated advanced renal cell carcinoma, in combination with nivolumab. Treatment of adult and pediatric patients 12 years of age and older with MSI‐H or dMMR metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan, in combination with nivolumab. 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.

Structure

Recombinant human IgG1 kappa monoclonal antibody.

Mechanism of action

Binds to the CTLA‐4 cell membrane receptor and blocks the interaction of CTLA‐4 with its ligands, CD80 and CD86.

Pharmacokinetics

The pharmacokinetics of ipilimumab is linear in the dose range of 0.3 mg/kg to 10 mg/kg. Following administration of ipilimumab every 3 weeks, the systemic accumulation was 1.5‐fold or less. Steady‐state concentrations of ipilimumab were reached by the third dose; the mean minimum concentration at steady state was 19.4 mcg/mL at 3 mg/kg and 58.1 mcg/mL at 10 mg/kg every 3 weeks. The mean (percent coefficient of variation) terminal half‐life was 15.4 days (34%) and the mean (percent coefficient of variation) CL was 16.8 mL/h (38%). The CL of ipilimumab was unchanged in presence of anti‐ipilimumab antibodies.

Prior approvals (before March 10, 2020)

Treatment of unresectable or metastatic melanoma in adults and pediatric patients (12 years and older).

Adjuvant treatment of patients with cutaneous melanoma with pathologic involvement of regional lymph nodes of more than 1 mm who have undergone complete resection, including total lymphadenectomy.

Treatment of patients with intermediate or poor risk, previously untreated advanced renal cell carcinoma, in combination with nivolumab.

Treatment of adult and pediatric patients 12 years of age and older with MSI‐H or dMMR metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan, in combination with nivolumab. 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: CL, clearance; CTLA‐4, cytotoxic T‐lymphocyte–associated antigen 4; dMMR, mismatch repair deficient; MSI‐H, microsatellite instability high.

Source: Ipilimumab U.S. Package Insert dated September 20, 2019 (Supplement 104).