On April 19th, 2016 Astex Pharmaceuticals, Inc., a pharmaceutical company dedicated to the development of novel small molecule oncology therapeutics, reported that it has entered into a clinical collaboration with Genentech (Press release, Astex Pharmaceuticals, APR 19, 2016, View Source [SID:1234511097]). Schedule your 30 min Free 1stOncology Demo! The collaboration will evaluate the potential for combining Astex’s next generation hypomethylating agent, guadecitabine (SGI-110), with Genentech’s investigational anti-PD-L1 monoclonal antibody, atezolizumab, in the treatment of acute myeloid leukemia (AML). An initial Phase 1b study will investigate the safety and pharmacology of the combination.
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
The collaboration will 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 tumor associated antigens, as well as inducing or upregulating the expression of immune checkpoints such as programmed death 1 (PD-1), and programmed deathligand 1 (PD-L1) and 2 (PD-L2), rendering the tumor more immunogenic, and more susceptible to treatment with a checkpoint inhibitor antibody such as atezolizumab (Maio et al, Clin. Cancer Research, 2015; 21:4040-47).
Guadecitabine has been evaluated in multiple Phase 1 and Phase 2 trials to investigate its potential in the treatment of a range of cancers. Astex has recently completed a large (over 400 patients) randomized Phase 1/2 study in patients with myelodysplastic syndromes (MDS) or AML. The trial included a Phase I dose escalation stage (93 patients) and a randomized Phase 2 stage (308 patients) that investigated four different patient populations: treatment naïve and relapsed/refractory AML and MDS. The trial demonstrated that guadecitabine was clinically active and well tolerated in all four patient groups. The results from the Phase 1 portion of the trial were recently published in Lancet Oncology (http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2815%2900038-8/abstract). Additional information about the study can be found online at View Source
Guadecitabine is now being evaluated in the ASTRAL-1 trial, a large, global, randomized 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. Additional information about the study can be found online at: View Source
Mohammad Azab, Astex’s President and Chief Medical Officer said: "We are delighted that Genentech has chosen to partner with Astex on this exciting study. 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. Astex is committed to exploring the broad potential of guadecitabine as a "backbone" therapy for use in immunotherapy combinations.
About Acute Myeloid Leukemia (AML)
AML is the most common form of leukemia in adults. Over 20,000 new cases of AML are diagnosed annually in the US. Although 60%-75% of AML patients 60 years old is significantly worse with response rates < 50%, cure rates remaining at <10% and a median survival of 1 year. These figures have not significantly improved within the last 3 decades. These patients have few therapeutic options. Effective, less toxic therapies are needed for the treatment of AML, particularly for elderly patients whose comorbidities make them unfit for intensive therapy.
About Guadecitabine (SGI-110)
Guadecitabine is a novel next-generation, small molecule DNA hypomethylating agent formulated as a single, small volume, subcutaneous injection. The product was designed to deliver longer exposure to the active metabolite, decitabine, compared to iv decitabine, and more efficient delivery into key tissues, including the bone marrow. Guadecitabine demonstrated activity in restoring silenced tumor suppressor gene expression in cancer cells by reversal of DNA methylation and inducing responses in previously treated MDS and AML patients. Guadecitabine is wholly owned by Astex Pharmaceuticals.
About Atezolizumab
Atezolizumab (also known as MPDL3280A) is an investigational humanized monoclonal antibody designed to target and bind to a protein called PD-L1, which is expressed on tumor cells and tumorinfiltrating immune cells. PD-L1 interacts with PD-1 and B7.1, both found on the surface of T cells, thereby inhibiting T cell function. By blocking this interaction, atezolizumab may enable the activation of T cells, restoring their ability to effectively detect and attack tumour cells. Atezolizumab is being developed by Genentech (South San Francisco, CA, USA), a member of the Roche Group.