[Exposure-Response Analysis] Exposure-Response Analyses of Tremelimumab Monotherapy or in Combination with Durvalumab in Patients with Unresectable Hepatocellular Carcinoma

2023-02-16

Abstract
Purpose: A novel single-dose regimen of 300 mg tremelimumab in combination with durvalumab [Single Tremelimumab Regular Interval Durvalumab (STRIDE)] has demonstrated a favorable benefit-risk profile in the phase I/II Study 22 (NCT02519348) and phase III HIMALAYA study (NCT03298451). This study evaluated the pharmacokinetics, exposure-response, and exposure-pharmacodynamics relationships of tremelimumab in patients with unresectable hepatocellular carcinoma (uHCC).

Patients and methods: A previous tremelimumab population pharmacokinetic model was validated using data from parts 2 ......

[Exposure-Response Analysis] Exposure-Response Efficacy and Safety Analyses of Tremelimumab as Monotherapy or in Combination with Durvalumab in Patients with Unresectable Hepatocellular Carcinoma (uHCC)

2021-01-22

Abstract
Background: In a phase II study in uHCC (Study 22, NCT02519348), a novel, priming combination regimen of tremelimumab (T; anti-CTLA-4) and durvalumab (D; anti-PD-L1) (T300+D) has shown favorable clinical activity vs each agent as monotherapy or vs another combination (T75+D). The analyses presented here assess the pharmacokinetics (PK) and relationships between tremelimumab exposure, as monotherapy or in combination, and safety, efficacy, and pharmacodynamics (PD) in this study. Methods: Overall, 216 pts were included in these analyses (T, n=65; T300+D, n=72; T75+D, n=79). Safety, an......

[Exposure-Response Analysis] Exposure-Response Relationship of the Bruton Tyrosine Kinase Inhibitor, Zanubrutinib (BGB-3111) in Patients with Hematologic Malignancies.

2019-11-13

Background:

Zanubrutinib (BGB-3111) is a highly selective, potent, irreversible inhibitor of Bruton tyrosine kinase (BTK), currently in phase 3 development for the treatment of hematologic malignancies, including mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL) and Waldenström's macroglobulinemia (WM). In a dose escalation study evaluating doses of 40, 80, 160, and 320 mg once daily and 160 mg twice daily, no dose limiting toxicities were observed and maximum tolerated dose (MTD) was not established. Objective responses have been observed in patients with various B-cell malign......

[Exposure-Response Analysis] Exposure-Response Relationship of the Bruton Tyrosine Kinase Inhibitor, Zanubrutinib (BGB-3111) in Patients with Hematologic Malignancies

2019-11-13

Abstract
Background:

Zanubrutinib (BGB-3111) is a highly selective, potent, irreversible inhibitor of Bruton tyrosine kinase (BTK), currently in phase 3 development for the treatment of hematologic malignancies, including mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL) and Waldenström's macroglobulinemia (WM). In a dose escalation study evaluating doses of 40, 80, 160, and 320 mg once daily and 160 mg twice daily, no dose limiting toxicities were observed and maximum tolerated dose (MTD) was not established. Objective responses have been observed in patients with various B-c......

[Exposure-Response Analysis] Tislelizumab Exposure-Response Analyses of Efficacy and Safety in Patients with Advanced Tumors.

2019-09-30

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 class......