BERKELEY, Calif.—Aduro Biotech, Inc. presented five posters highlighting ongoing clinical trials and pre-clinical programs investigating its novel immunotherapies in development for the treatment of cancer at the Society for Immunotherapy of Cancer Annual Meeting held in National Harbor, Maryland
In a poster presented on Saturday, November 7, 2015 by Nitya Nair, Ph.D., scientist at Aduro, updated safety and efficacy data were shared from the Phase 2a clinical trial of Aduro’s novel immunotherapy CRS-207 in combination with GVAX Pancreas in patients with metastatic pancreatic cancer. Seven patients treated with this regimen survived for more than three years, with one patient continuing to receive the combination regimen. In addition, the poster highlighted key biomarker findings in 38 patients from the 93-patient trial which demonstrated a statistically significant correlation between levels of certain immune cells in the peripheral blood and overall survival. Specifically, the data showed elevated subsets of CD8+ immune T cells at baseline and at seven weeks after treatment initiation resulted in better performance outcomes. Conversely, an increase in subsets of certain myeloid cells (CD14+) at the same time points was associated with worse outcomes.
In another poster presented by Jeremy Foote, Ph.D., D.V.M., at Johns Hopkins University School of Medicine, encouraging preclinical results demonstrated that direct intratumoral injection of Aduro’s human STING-activating CDN (cyclic dinucleotide) immunotherapy in a model of HER2+ breast cancer resulted in complete eradication of the injected tumor as well as distant untreated tumors. In addition, the responses observed were durable, showing long lasting immunologic memory and anti-tumor protection when CDN-treated mice were re-challenged with HER2+ breast cancer tumor cells. In a much more challenging tumor model that is profoundly tolerant for the HER2 tumor antigen and with greater similarity to advanced cancer patients, treatment combining a single intratumoral injection of CDN with cyclophosphamide and anti-PD-L1 immune checkpoint antibodies resulted in pronounced inhibition of tumor growth. Together, these results demonstrate that activation of the STING pathway in the tumor microenvironment by the direct injection of Aduro’s proprietary CDNs results in the development of tumor antigen-specific immunity and tumor regression.
Separately, three additional posters were presented at the SITC meeting that provide details on the ongoing trials, namely the Phase 2b STELLAR trial in pancreatic cancer, an expanded cohort in a Phase 1b trial in mesothelioma and a Phase 1 trial in grade 3/4 gliomas, including glioblastoma multiforme.
The STELLAR (Safety and Therapeutic Efficacy of Live-attenuated Listeria/GVAX with Anti-PD1 Regimen) poster highlighted the randomized, controlled trial that now has an increased enrollment target of 102 adult patients with metastatic pancreatic cancer who have failed one prior chemotherapy regimen for metastatic disease. Patients are randomized equally to one of two arms: Arm A with CRS-207/GVAX Pancreas vaccine and nivolumab or Arm B with CRS-207/GVAX Pancreas vaccine. The primary objective of this study is to compare the overall survival of patients in Arm A and Arm B. Secondary endpoints include evaluation of clinical and immune response and safety. For more information, please visit ClinicalTrials.gov (Identifier: NCT02243371). With the increased enrollment target, Aduro now expects enrollment to be completed in the second half of 2016 and continues to expect interim data in the second half of 2016.
A separate poster highlighted an expansion cohort in the Phase 1b clinical trial of CRS-207 in combination with chemotherapy. In this second cohort, eligible patients will first receive low-dose cyclophosphamide (Cy) one day prior to receiving two prime vaccinations with CRS-207 two weeks apart, followed by up to six cycles of standard-of-care pemetrexed and cisplatin chemotherapy three weeks apart and two CRS-207 boost vaccinations three weeks apart. Cy has been added to the regimen for the second cohort of patients to evaluate whether the triplet regimen improves tumor responses by reducing regulatory T-cells with Cy. Clinically stable patients will continue to receive Cy/CRS-207 maintenance vaccinations every eight weeks and are followed every eight weeks until disease progression. Objectives of the study are safety, immunogenicity, objective tumor responses and tumor marker kinetics.
Another poster provided an overview of the investigator-sponsored Phase 1 trial to evaluate the safety and immunogenicity of Aduro’s ADU-623 in grade 3/4 gliomas (including anaplastic astrocytomas and glioblastoma brain cancers). This is a dose-escalation trial enrolling up to 18 patients. The primary objective of the trial is to identify the maximum tolerated dose and characterize the safety profile of the ADU-623 vaccine in patients with treated and recurrent grade 3/4 astrocytomas. For more information, please visit ClinicalTrials.gov (Identifier: NCT01967758).
CRS-207 is one of a family of product candidates based on Aduro’s live-attenuated, double-deleted (LADD) Listeria monocytogenes immunotherapy platform that induces a potent innate and T cell-mediated adaptive immune response. CRS-207 has been engineered to express the tumor-associated antigen mesothelin, which is over-expressed in many cancers including mesothelioma and pancreatic, non-small cell lung, ovarian, endometrial and gastric cancers.
Aduro’s proprietary CDN product candidates are synthetic small molecule immune modulators that are designed to target and activate a receptor known as the Stimulator of Interferon Genes, or STING. The STING receptor is generally expressed at high levels in immune cells, including dendritic cells. Once activated, the STING receptor initiates a profound innate immune response through multiple pathways, inducing the expression of a broad profile of cytokines, including interferons and chemokines. This subsequently leads to the development of an effective tumor antigen-specific T cell adaptive immune response.
LADD is Aduro’s proprietary platform of live-attenuated double-deleted Listeria monocytogenes strains that have been engineered to induce a potent innate immune response and to express tumor-associated antigens to induce tumor-specific T cell-mediated immunity. ADU-623 is engineered to express EGFRvIII and NY-ESO-1, which are expressed in glioblastoma and other cancers.
Aduro Biotech, Inc. is a clinical-stage immunotherapy company focused on the discovery, development and commercialization of therapies that transform the treatment of challenging diseases. Aduro's technology platforms, which are designed to harness the body's natural immune system, are being investigated in cancer indications and have the potential to expand into autoimmune and infectious diseases. Aduro's LADD technology platform is based on proprietary attenuated strains of Listeria that have been engineered to express tumor-associated antigens to induce specific and targeted immune responses. Based on compelling clinical data in advanced cancers, this platform is being developed as a treatment for multiple indications, including pancreatic, lung and prostate cancers, mesothelioma and glioblastoma. Aduro's cyclic dinucleotide (CDN) platform is designed to activate the intracellular STING receptor, resulting in a potent tumor-specific immune response. Aduro’s B-select monoclonal antibody platform includes a number of immune modulating assets in research and preclinical development. Aduro is collaborating with leading global pharmaceutical companies to expand its products and technology platforms.