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
4242 - HIV, HBV and HCV screening practices in oncology: a cross-sectional interregional survey
Presenter: Isabelle Poizot-Martin
Session: Poster Display session 1
Resources:
Abstract
1267 - Genetic landscape of KEAP1 and NFE2L2 mutated cancers from the AACR GENIE database
Presenter: Mark Zaki
Session: Poster Display session 1
Resources:
Abstract
878 - β-arrestin1 is involved in the Ras-induced malignant transformation
Presenter: Takashi Shibano
Session: Poster Display session 1
Resources:
Abstract
4143 - Incidence of second cancer among PLWHIV: retrospective observational study of a series of 601 patients in the French CANCERVIH network
Presenter: Jean-Philippe Spano
Session: Poster Display session 1
Resources:
Abstract
5145 - A challenging task – Identifying carcinoma of unknown primary (CUP) patients according to ESMO guidelines: the CUPISCO trial experience
Presenter: Chantal Pauli
Session: Poster Display session 1
Resources:
Abstract
1737 - Incidence and Outcome of chronic lymphocytic leukemia with Deletion 17p: An Indian experience; challenges and opportunities
Presenter: Ajay Gogia
Session: Poster Display session 1
Resources:
Abstract
2596 - Driving solo? Investigation into collaborating mutations in SDH-deficient neoplasia
Presenter: Jonathan Killian
Session: Poster Display session 1
Resources:
Abstract
1499 - The potential of a novel antiangiogenic VEGFR1-D2 binding peptide in oncology therapeutics
Presenter: Afsaneh Sadre Momtaz
Session: Poster Display session 1
Resources:
Abstract
1775 - First-in-human phase I study of TAS-117, an allosteric AKT inhibitor, in patients with advanced solid tumors
Presenter: Mayu Yunokawa
Session: Poster Display session 1
Resources:
Abstract
4584 - First-in-human study of ABBV-621 in patients (pts) with previously treated sold tumors: Dose-optimization cohorts
Presenter: Emiliano Calvo
Session: Poster Display session 1
Resources:
Abstract