Clinical dose rationale of tislelizumab in patients with solid or hematological advanced tumors

• DOI: 10.1111/cts.13769
• Publication Date: 2024-03-22T07:13:50Z
• Authors: Tian Yu; Xiangyu Liu; Chi‐Yuan Wu; Zhiyu Tang; Hongwei Wang; Patrick Schnell; Ya Wan; Kun Wang; Lucy Liu; Yuying Gao; Srikumar Sahasran...; Nageshwar Budha
• Keywords: Hematologic Neoplasms; Solid tumor

Tislelizumab, an anti-programmed cell death protein 1 monoclonal antibody, has demonstrated improved survival benefits over standard of care for multiple cancer indications. We present the clinical rationale and data supporting tislelizumab dose recommendation in patients with advanced tumors. The phase I, first-in-human, dose-finding BGB-A317-001 study (data cutoff [DCO]: August 2017) examined following dosing regimens: 0.5-10 mg/kg every 2 weeks (q2w), 2-5 q2w or q3w, 200 mg q3w. Similar objective response rates (ORRs) were reported 5 q3w cohorts. Safety outcomes (grade ≥3 adverse events [AEs], AEs leading to modification/discontinuation, immune-mediated AEs, infusion-related reactions) generally comparable across range examined. These results, alongside convenience a fixed dose, formed basis choosing as recommended regimen further use. Pooled exposure-response (E-R) analyses by logistic regression using from (DCO: 2020) three additional I/II studies (DCOs: 2018-2020) showed no statistically significant correlation between pharmacokinetic exposure ORR solid tumor types classical Hodgkin's lymphoma, nor was associated any safety end points evaluated tested. Hence, relatively flat E-R relationship. Overall, totality data, including efficacy, safety, analyses, together relative provided