CCR4 antagonists are a promising combinatorial agent for the future

As novel immuno-oncology (IO) drugs become established in the market, a new trend of combinatorial treatments is arising. The race to develop combinatorial drugs is increasing with more companies including IO potentiating drugs in their pipelines and investigating these in combination with established IO drugs, says GlobalData, a leading data and analytics company.

Miguel Ferreira, MSc, Oncology and Hematology Analyst at GlobalData, says: “One of the multiple potential IO combination targets being explored is C-C chemokine receptor 4 (CCR4), currently with only one drug in the pipeline; Hanmi and RAPT Therapeutics’ FLX-475. FLX-475 stands out as an oral formulation despite its possible second to market status behind mogamulizumab, a CCR4 antagonist approved for the treatment of Sezary disease since September 2018.”

Cancer cells exploit CCR4 receptors to recruit immuno-suppressive regulatory T-cells (Tregs) to the tumour microenvironment. This mechanism can negatively affect the ability of immune checkpoint inhibitors (ICIs) to reverse immune suppression. Therefore, CCR4 antagonists are one strategy to tackle this pathway and potentiate ICI drug response.

Ferreira continued: “In addition to demonstrating excellent pharmacokinetic parameters and having no reported dose-limiting adverse events, FLX-475 is notable due to being involved in a trial in combination with Keytruda – a popular choice for combination therapy trials and which is currently being tested in a total of 524 trials out of the 1838 ongoing Phase I-III trials exploring ICI combination strategies.

GlobalData believes that IO drug combinations are well positioned to lead the global cancer market and that ideal combinations for various tumor types are yet to be established. Furthermore, given FLX-475’s ability to complement ICI treatment without adding to the toxicity and its involvement with Keytruda in the pipeline makes it a promising combination agent for the future. GlobalData is forecasting the global commercial launch of FLX-475 monotherapy in Q4 2023, with combination approvals coming soon after.”

More Media