Astex Pharma and Genentech Forge a Clinical Trial Deal for Acute Myeloid Leukemia

Astex Pharma and Genentech Forge a Clinical Trial Deal for Acute Myeloid Leukemia
April 19, 2016
By Alex Keown, Breaking News Staff

PLEASANTON, Calif. -- Astex Pharmaceuticals, Inc. , a subsidiary of Japan-based Otsuka Pharmaceutical Co. Ltd., forged a deal with Genentech to develop a combination treatment for acute myeloid leukemia (AML).

Financial terms of the deal between the companies were not disclosed. However, Astex said the two companies will collaborate to explore the combination of Astex’s next generation hypomethylating agent, guadecitabine (SGI-110), with Genentech’s investigational anti-PD-L1 monoclonal antibody, atezolizumab. The companies plan to launch into an initial Phase Ib study to investigate the safety and pharmacology of the combination, Astex said in a statement this morning.

AML is the most common form of leukemia in adults, with more than 20,000 new cases diagnosed annually in the United States.

Astex said the combination therapy of atezolizumab and guadecitabine will test the belief that upfront “priming” of patients’ immune systems with guadecitabine, an epigenetic investigational drug, may result in enhanced responses to immunotherapy. Guadecitabine is a small molecule DNA hypomethylating agent formulated as a single, small volume, subcutaneous injection. Guadecitabine reverses aberrant DNA methylation, one of the key mechanisms associated with AML and other malignancies, by inhibiting DNA methyltransferase enzymes. In October 2015, the U.S. Food and Drug Administration (FDA) granted an orphan drug designation for Astex’s guadecitabine.

The combination treatment 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 death-ligand 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,” Astex said. Genentech’s atezolizumab, an investigational monoclonal antibody designed to interfere with a protein called PD-L1 (Programmed Death Ligand-1), has shown clinical trial success in shrinking tumors in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease expressed PD-L1.

“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,” Mohammad Azab, Astex’s president and chief medical officer, said in a statement.

Astex’s guadecitabine has been evaluated in multiple Phase I and Phase II trials to investigate its potential in the treatment of a range of cancers. A recent Phase I/II study of AML patients demonstrated that guadecitabine was clinically active and well tolerated. Now the drug is being evaluated in an 800-patient study in treatment naïve AML patients who are unfit to receive, or unsuitable for, intensive induction chemotherapy. The trial compares guadecitabine with other drugs, such as cytarabine, decitabine or azacitidine.

Genentech’s atezolizumab is also being investigated in other combination treatments. Genentech and Janssen Research & Development struck a deal earlier this year to initiate two studies to determine the safety and tolerability of daratumumab (Darzalex) and atezolizumab for treatment of in multiple myeloma and in solid tumor. In addition to its deal with Janssen, Genentech has struck other deals to test the drug. In June 2015, Amgen announced a collaboration on a Phase Ib clinical trial to evaluate talimogene laherparepvec combined with atezolizumab for the treatment of triple-negative breast cancer and colorectal cancer with liver metastases. Genentech and Clovis struck a deal to test a lung cancer dual combo therapy that utilizes Clovis’ investigational oral medication rociletinib and atezolizumab.

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