Abstract 2618
Background
Tislelizumab, an investigational humanized IgG4 monoclonal antibody, 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. Tislelizumab exposure-response (E-R) relationships for efficacy and safety endpoints in subjects with advanced tumors were evaluated to inform the benefit-risk assessment and to explore the feasibility of alternative dosing schedules.
Methods
The analyses used data from patients with advanced solid tumors (n = 745) and classical Hodgkin lymphoma (cHL, n = 70) from three clinical studies who received tislelizumab doses ranging from 0.5 to 10 mg/kg (including current recommended dose of 200 mg Q3W). E-R efficacy analyses were performed for overall response rate (ORR) and E-R safety analyses were performed for immune-related adverse events (irAEs), infusion-related AEs, and AEs ≥ grade 3, AEs leading to dose modification, and drug discontinuation using logistic regression models. Impact of tumor type on E-R efficacy and safety analyses were also investigated.
Results
E-R analysis indicated that there was slight trend for increase in ORR in solid tumors with steady-state maximum concentration, minimum concentration and average concentrations over the dose range tested. However, the increase in ORR over the exposure range was not considered to be clinically significant. Tislelizumab exposure was not associated with ORR in cHL patients. No E-R relationships were observed for safety endpoints irAEs, infusion-related AEs, AEs ≥ grade 3, AEs leading to drug discontinuation or dose modification among tumor types. Predictions with an alternate dose regimen of 400 mg Q6W showed that clinically significant differences in ORR and safety were not expected, compared with 200 mg Q3W.
Conclusions
There was a lack of clinically significant E-R relationships for ORR and safety endpoints across a variety of advanced solid tumors and cHL for tislelizumab. These findings support the current dose regimen of 200 mg Q3W and further clinical testing of alternative dosing schedules that produce comparable exposure (eg, 400 mg Q6W).
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, Ltd.
Disclosure
C-Y. Wu: Full / Part-time employment: BeiGene, Ltd. N. Budha: Full / Part-time employment: BeiGene, Ltd. H. Castro: Full / Part-time employment: BeiGene, Ltd. A. Nkobena: Full / Part-time employment: BeiGene, Ltd. Y. Ben: Full / Part-time employment: BeiGene, Ltd. Sahasranaman: Full / Part-time employment: BeiGene, Ltd. All other authors have declared no conflicts of interest.
Resources from the same session
4321 - Health-related quality of life of advanced melanoma survivors treated with CTLA-4 immune checkpoint inhibition: a matched cohort study
Presenter: Annelies Boekhout
Session: Poster Display session 1
Resources:
Abstract
779 - Capecitabine vs Cisplatin along with concurrent radiotherapy in the treatment of inoperable lower esophageal cancers focusing on TWISTT score and QOL
Presenter: Goutham Anugu
Session: Poster Display session 1
Resources:
Abstract
5914 - Cancer, Mental Health and End Life Simulation (CAMhELS): A novel effectiveness evaluation.
Presenter: Asanga Fernando
Session: Poster Display session 1
Resources:
Abstract
2597 - Cancer patients’ expectations and understanding about their disease
Presenter: Mónica Pinho
Session: Poster Display session 1
Resources:
Abstract
5187 - Impact of patients’ death on oncologists and coping strategies: An online survey
Presenter: Soumaya Labidi
Session: Poster Display session 1
Resources:
Abstract
4579 - Clinical benefit from late lines of therapy offered to patients treated in a tertiary referral centre
Presenter: Andrea Sbrana
Session: Poster Display session 1
Resources:
Abstract
5058 - Preparedness for caregiving in caregivers of cancer patients
Presenter: Hatice Yakar
Session: Poster Display session 1
Resources:
Abstract
5917 - Oncologic Emergency Medicine in the real world: A survey and proposal for improvement
Presenter: Carintia Dorta Pérez
Session: Poster Display session 1
Resources:
Abstract
4077 - The Reality of Critical Cancer Patients in a Polyvalent Intensive Care Unit
Presenter: Tiago Filipe Da Cruz Tomas
Session: Poster Display session 1
Resources:
Abstract
1728 - A phase III trial evaluating olanzapine 5 mg for the prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin: J-FORCE Study
Presenter: Hironobu Hashimoto
Session: Poster Display session 1
Resources:
Abstract