Astex, Genentech partner to explore combination treatment for acute myeloid leukemia

The alliance will evaluate the potential for combining Astex’s guadecitabine (SGI-110) small molecule DNA hypomethylating agent with Genentech’s atezolizumab investigational anti-PD-L1 monoclonal antibody.

The safety and pharmacology of the combination will be assessed in an initial phase 1b study.

Under the collaboration, the companies will test the hypothesis that upfront priming of patients’ immune systems with guadecitabine could result in improved responses to immunotherapy.

Astex said the hypothesis is based on the observation that guadecitabine demethylates and induces re-expression of tumor associated antigens, as well as inducing or upregulating the expression of immune checkpoints like programmed death 1 (PD-1), and programmed death-ligand 1 (PD-L1) and 2 (PD-L2).

Guadecitabine has been assessed in several phase 1 and phase 2 trials to investigate its potential in treating a range of cancers.

Astex has recently completed a randomized phase 1/2 study in patients with myelodysplastic syndromes or AML. It is also being evaluated in several other trials.

Atezolizumab is designed to target and bind to a protein called PD-L1, which is found on tumor cells and tumor-infiltrating immune cells.

Astex Pharmaceuticals president and chief medical officer said: "The idea of combining epigenetic therapies such as guadecitabine with immune checkpoint inhibitors such as atezolizumab, has the potential to open up new therapeutic options with enhanced outcomes for patients with a range of cancer types."