28 September 2018 - - The first patient has been treated in US-based biopharmaceutical company FLX Bio, Inc.'s Phase 1/2 clinical trial of FLX475 in patients with various advanced cancers. FLX475 is an oral, small molecule CCR4 antagonist that selectively inhibits migration of regulatory T cells into the tumor microenvironment, the company said.

The open-label, dose-escalation and cohort expansion Phase 1/2 study will enroll patients with multiple types of cancer at leading cancer centers across the United States, Australia and Asia.

The trial will evaluate the safety and tolerability of FLX475 as a monotherapy and in combination with pembrolizumab. In addition, the study will evaluate changes in the tumor microenvironment and the antitumor activity of both monotherapy and combination therapy.

Patients with tumors positive for the Epstein-Barr Virus, which has been shown to be an indicator of tumors with a higher number of Treg cells, will be enrolled in a biomarker-selected cohort. Tumors that can be positive for EBV include nasopharyngeal cancer and Hodgkin lymphoma.

In addition, the company intends to enroll patients with tumors that express high levels of CCR4 receptor and ligands, which include non-small cell lung cancer, head and neck cancer, triple negative breast cancer, and cervical cancer.

FLX475 is a best-in-class oral, small molecule antagonist of CCR4.

FLX Bio has completed a study of FLX475 in healthy volunteers, demonstrating that the compound is safe with excellent pharmacokinetic and pharmacodynamic properties.

In preclinical studies, FLX475 inhibited tumor growth and increased tumor regression as a single agent. In addition, FLX475 enhanced the antitumor effects of various checkpoint inhibitors including anti-PD-L1 and anti-CTLA4 antibodies as well as immune agonists such as anti-4-1BB antibodies.

FLX475 also has the potential to enhance cell-based immunotherapies such as CAR-T and cancer vaccines.

Unlike antibodies to CCR4, FLX475 selectively blocks the recruitment of regulatory T cells to the tumor site and does not deplete cells beneficial to an antitumor response or regulatory T cells in healthy tissue such as blood, spleen and skin cells.

FLX Bio is a privately-held biopharmaceutical company focused on the discovery, development and commercialization of best-in-class, oral small molecule therapeutics for the treatment of cancers and other immune disorders.

Its lead compounds inhibit the CCR4 pathway which plays a key role in both suppressing the immune response to cancer and in the initiation, progression and persistence of allergic inflammation.

Located in South San Francisco, Calif., and funded by leading investors, including The Column Group, Kleiner Perkins, Topspin Partners, GV (formerly Google Ventures) and Celgene Corp., FLX Bio has assembled a leadership team and advisory group with a proven track record of success and team of scientists with substantial knowledge and expertise in drug discovery and translational areas essential to execute on this approach.