Induce-1: A Phase I Open-Label Study Of Gsk3359609, An Icos Agonist Antibody, Administered Alone And In Combination With Pembrolizumab In Patients With Advanced Solid Tumors.

Background Inducible T cell Co-Stimulator (ICOS), a member of the CD28/B7/CTLA immunoglobulin receptor superfamily, is expressed on T cells after engagement with cognate antigen and activation. ICOS provides a co-stimulatory signal augmenting T cell proliferation, cytokine production, cytotoxic function and survival. GSK3359609 is a humanized IgG4 antibody selected for its potent binding agonist activity against human ICOS. Rationale for targeting ICOS with GSK33359609 as a monotherapy and in combination with other cancer immunotherapies such as pembrolizumab is supported by preclinical evidence. Methods INDUCE-1 is a first in human study evaluating safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary antitumor activity of GSK3359609 administered as an intravenous (IV) infusion once every three weeks (Q3W) alone (Part 1) and in combination with 200 mg pembrolizumab (Q3W IV infusion) or other immunotherapy (Part 2) in approximately 304 adult patients. In the dose escalation phase, eligible patients are required to have selected, relapsed/refractory solid tumors. Accelerated titration design is planned for the first 3 dose levels in Part 1, with 1 patient enrolled at each dose level; modified toxicity probability interval method will inform on subsequent dose escalation decisions (minimum 3 patients per dose level), and maximum tolerated dose or maximum administered dose determination. In the expansion phase, cohorts may be defined by factors such as tumor histology, biomarker features, or prior treatment. More than one GSK3359609 dose level may be evaluated in a single expansion cohort by patient random assignment. Tumor biopsies (before and on-treatment) are optional in escalation and required in expansion to provide biomarker data that may inform on optimal dose selection as well as mechanistic understanding of GSK3359609 activity. Immune-related Response Evaluation Criteria in Solid Tumors will be the primary measure of clinical activity. As of 12 January 2017, no dose limiting toxicities (DLT) were observed in the first 2 dose levels of GSK3359609 monotherapy; dose level 3 cohort enrollment is completed and under observation for DLTs. ClinicalTrials.gov identifier: NCT02723955 Study is funded by GlaxoSmithKline and is in collaboration with Merck u0026 Co, Inc Citation Format: Eric Angevin, Todd M. Bauer, Catherine E. Ellis, Hui Gan, Rigel Hall, Aaron Hansen, Axel Hoos, Roxanne C. Jewell, Jessica Katz, Juan Martin-Liberal, Michele Maio, Patrick A. Mayes, Jolly Mazumdar, Michael Millward, Danny Rischin, Jan H. Schellens, Sapna Yadavilli, Helen Zhou. INDUCE-1: a phase I open-label study of GSK3359609, an ICOS agonist antibody, administered alone and in combination with pembrolizumab in patients with selected, advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT039. doi:10.1158/1538-7445.AM2017-CT039