Astex Pharmaceuticals has entered a clinical collaboration with Genentech to evaluate the potential of combining guadecitabine (SGI-110) with atezolizumab in the treatment of acute myeloid leukaemia (AML).
Guadecitabine is Astex’s next-generation hypomethylating agent, while atezolizumab is an investigational anti-PD-L1 monoclonal antibody of Genentech.
An initial Phase lb study will examine the safety and pharmacology of the combination.
The newly formed collaboration will also test the hypothesis that upfront priming of patients’ immune systems with guadecitabine, an epigenetic investigational drug, may result in enhanced responses to immunotherapy.
The hypothesis is based on the observation that guadecitabine demethylates and induces re-expression of tumour related antigens, as well as inducing or upregulating the expression of immune checkpoints including programmed death 1 (PD-1), and programmed death-ligand 1 (PD-L1) and 2 (PD-L2), rendering the tumour more immunogenic, and more susceptible to treatment with a checkpoint inhibitor antibody such as atezolizumab.
Guadecitabine has already been evaluated in multiple Phase l and Phase ll trials to investigate its potential in treatment of a range of cancers.
Astex has recently completed a randomised Phase l/ll study in over 400 patients with myelodysplastic syndromes (MDS) or AML, which is the most common form of leukaemia in adults.
The trial included a Phase I dose escalation stage in 93 patients and a randomised Phase l stage in 308 patients that investigated four different patient populations, treatment naïve and relapsed/refractory AML and MDS.
The trial showed that guadecitabine was clinically active and well tolerated in all four patient groups.
Guadecitabine is currently being evaluated in the ASTRAL-1 trial, a large, global, randomised 800-patient study in treatment naïve AML patients who are unfit to receive, or unsuitable for, intensive induction chemotherapy.
The trial compares guadecitabine with physician’s choice of low-dose cytarabine, decitabine or azacitidine.