Population Pharmacokinetics of Ipilimumab in Combination With Nivolumab in Patients With Advanced Solid Tumors. 2020

Kinjal Sanghavi, and Jason Zhang, and Xiaochen Zhao, and Yan Feng, and Paul Statkevich, and Jennifer Sheng, and Amit Roy, and Heather E Vezina
Bristol-Myers Squibb, Princeton, New Jersey, USA.

Ipilimumab is a fully human monoclonal antibody approved for the treatment of melanoma as monotherapy and for the treatment of melanoma, renal cell carcinoma, and colorectal cancer in combination with nivolumab. Ipilimumab time-varying clearance (CL) was assessed by a population pharmacokinetics (PPK) model developed using statistically significant covariates identified in a previous PPK analysis plus additional covariates. Data from 3,411 patients who received ipilimumab 0.3-10 mg/kg alone or in combination with nivolumab in 16 clinical trials were analyzed. Ipilimumab CL decreased over time; the change in CL was greater in patients treated with nivolumab combination than ipilimumab alone and in responders vs. nonresponders. Time-varying covariates including body weight, lactate dehydrogenase, albumin, and performance status were evaluated on change in ipilimumab CL. In addition, ipilimumab CL was similar across different tumor types, nivolumab dosing regimens, and lines of therapy. These data suggest an association of ipilimumab CL with disease severity.

UI MeSH Term Description Entries
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000074324 Ipilimumab An anti-CTLA-4 ANTIGEN monoclonal antibody initially indicated for the treatment of certain types of metastatic MELANOMA. Its mode of actions may include blocking of CTLA-4 mediated inhibition of CYTOTOXIC T LYMPHOCYTES, allowing for more efficient destruction of target tumor cells. Anti-CTLA-4 MAb Ipilimumab,MDX 010,MDX-010,MDX-CTLA-4,MDX010,Yervoy,Anti CTLA 4 MAb Ipilimumab,Ipilimumab, Anti-CTLA-4 MAb,MDX CTLA 4
D000077594 Nivolumab A genetically engineered, fully humanized immunoglobulin G4 monoclonal antibody that binds to the PD-1 RECEPTOR, activating an immune response to tumor cells. It is used as monotherapy or in combination with IPILIMUMAB for the treatment of advanced malignant MELANOMA. It is also used in the treatment of advanced or recurring NON-SMALL CELL LUNG CANCER; RENAL CELL CARCINOMA; and HODGKIN'S LYMPHOMA. BMS-936558,MDX-1106,ONO-4538,Opdivo,BMS 936558,BMS936558,MDX 1106,MDX1106,ONO 4538,ONO4538
D000971 Antineoplastic Combined Chemotherapy Protocols The use of two or more chemicals simultaneously or sequentially in the drug therapy of neoplasms. The drugs need not be in the same dosage form. Anticancer Drug Combinations,Antineoplastic Agents, Combined,Antineoplastic Chemotherapy Protocols,Antineoplastic Drug Combinations,Cancer Chemotherapy Protocols,Chemotherapy Protocols, Antineoplastic,Drug Combinations, Antineoplastic,Antineoplastic Combined Chemotherapy Regimens,Combined Antineoplastic Agents,Agent, Combined Antineoplastic,Agents, Combined Antineoplastic,Anticancer Drug Combination,Antineoplastic Agent, Combined,Antineoplastic Chemotherapy Protocol,Antineoplastic Drug Combination,Cancer Chemotherapy Protocol,Chemotherapy Protocol, Antineoplastic,Chemotherapy Protocol, Cancer,Chemotherapy Protocols, Cancer,Combinations, Antineoplastic Drug,Combined Antineoplastic Agent,Drug Combination, Anticancer,Drug Combination, Antineoplastic,Drug Combinations, Anticancer,Protocol, Antineoplastic Chemotherapy,Protocol, Cancer Chemotherapy,Protocols, Antineoplastic Chemotherapy,Protocols, Cancer Chemotherapy
D012720 Severity of Illness Index Levels within a diagnostic group which are established by various measurement criteria applied to the seriousness of a patient's disorder. Illness Index Severities,Illness Index Severity
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor

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