Abstract 2563
Background
Tislelizumab, an investigational humanized IgG4 monoclonal antibody with high affinity and specificity for PD-1, was engineered to minimize binding to FcgR on macrophages in order to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. It has shown robust antitumor activity and was generally well-tolerated in patients with advanced solid tumors and with classical Hodgkin lymphoma (cHL). The objectives of this analysis were to develop a population pharmacokinetics (popPK) model and quantify the impact of demographic and disease characteristics on tislelizumab PK.
Methods
PopPK analysis was conducted using pooled data from three studies (001, 102, 203) in patients with advanced solid tumors and cHL. The dataset contained 5935 PK observations from 798 patients. A nonlinear mixed-effects modeling approach with first-order conditional estimation with interaction (FOCEI) method in NONMEM was used for the analysis. Covariates related to baseline demographics, tumor type, and tumor size on tislelizumab PK were investigated. Covariates were selected using a forward addition and backward elimination method.
Results
Tislelizumab PK exhibited linearity over a dose range of 0.5 - 10 mg/kg without time‐varying clearance. A three-compartment model with first-order elimination from the central compartment, and redistribution into the peripheral compartments best described the PK of tislelizumab. Clearance (CL), volume of distribution of central compartment (Vc), and terminal half-life were estimated to be 0.164 L/day, 2.92 L, and 25.9 days, respectively. Baseline tumor size, albumin and tumor type were significant covariates on CL, while body weight, sex and tumor type were significant covariates on Vc. However, sensitivity analysis showed that the impact of these covariates on tislelizumab exposures (area under the curve, maximum and trough concentrations) was not clinically significant.
Conclusions
The final popPK model adequately described the observed tislelizumab PK. Results support the use of the current clinical dose of 200 mg Q3W and no dose adjustment is necessary based on patients’ age, body weight, race, sex, tumor type and tumor size.
Clinical trial identification
BGB-A317-Study-001: NCT02407990 BGB-A317-203: NCT03209973 BGB-A317-102: CTR20160872.
Editorial acknowledgement
Legal entity responsible for the study
BeiGene, Ltd.
Funding
BeiGene.
Disclosure
C-Y. Wu: Full / Part-time employment: BeiGene, Ltd. T. Tang: Full / Part-time employment: BeiGene, Ltd. Y. Ben: Full / Part-time employment: BeiGene, Ltd. S. Sahasranaman: Full / Part-time employment: BeiGene, Ltd. All other authors have declared no conflicts of interest.
Resources from the same session
3305 - A phase I dose-escalation and expansion trial of intratumorally administered CV8102, alone and in combination with anti-PD-1 in patients with advanced solid tumors
Presenter: Jürgen Krauss
Session: Poster Display session 1
Resources:
Abstract
5353 - Phase 1/2 Study of 9-ING-41, a small molecule selective Glycogen Synthase Kinase-3 Beta (GSK-3β) Inhibitor, as a Single Agent and Combined with Chemotherapy, in Patients with Refractory Hematological Malignancies or Solid Tumors
Presenter: Benedito Carneiro
Session: Poster Display session 1
Resources:
Abstract
3946 - Trial in progress: a Phase I, open-label study of GSK1795091 administered in combination with immunotherapies in participants with advanced solid tumors (NCT03447314).
Presenter: Aaron Hansen
Session: Poster Display session 1
Resources:
Abstract
3449 - Radiographic Phenotyping to Identify Intracranial Disseminated Recurrence in Brain metastases Treated With Radiosurgery Using Contrast-enhanced MR Imaging
Presenter: CheYu Hsu
Session: Poster Display session 1
Resources:
Abstract
4553 - Association between TP53 mutations and efficacy of Osimertinib for brain metastasis from EGFR-mutant lung cancer
Presenter: Lijuan Chen
Session: Poster Display session 1
Resources:
Abstract
4942 - Response assessment of melanoma brain metastases treated by stereotactic radiotherapy or immunotherapy or both: a comparison of RECIST 1.1, RANO and iRANO criteria
Presenter: Emilie Le Rhun
Session: Poster Display session 1
Resources:
Abstract
3529 - Management of multiple brain metastases by Staged SRS focusing on utmost risk lesions
Presenter: shaoqun Li
Session: Poster Display session 1
Resources:
Abstract
5315 - Whole brain radiotherapy plus simultaneous in-field boost versus whole brain radiotherapy plus fractionated stereotactic radiotherapy for multiple brain metastases of non-small cell lung cancer
Presenter: Lu Li
Session: Poster Display session 1
Resources:
Abstract
1116 - 3D based texture analysis serving as potential diagnostic factor in discriminating primary central nervous system lymphoma from metastatic brain tumors: A preliminary study
Presenter: Wen Guo
Session: Poster Display session 1
Resources:
Abstract
5344 - Global trends in population-based survival for 303,169 adults diagnosed with glioblastoma in 44 countries during 2000-2014 (CONCORD-3)
Presenter: Fabio Girardi
Session: Poster Display session 1
Resources:
Abstract