Selection of the Recommended Phase 2 Dose for Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1.

ABSTRACT: Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (TGF-β "trap") fused to a human IgG1-blocking PD-L1, showed a manageable safety profile and clinical activity in phase I studies in patients with heavily pretreated advanced solid tumors. The recommended phase 2 dose (RP2D) was selected based on integration of modeling, simulations, and all available data. A 1,200-mg every 2 weeks (q2w) dose was predicted to maintain serum trough concentration (C_trough ) that inhibits all targets of bintrafusp alfa in circulation in > 95% of patients, and a 2,400-mg every 3 weeks (q3w) dose was predicted to have similar C_trough . A trend toward an association between exposure and efficacy variables and a relative

SUBMITTER: Vugmeyster Y 

PROVIDER: S-EPMC7484916 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature