On June 12, 2018 Asterias Biotherapeutics, Inc. (NYSE MKT:AST), a biotechnology company dedicated to developing cellular immunotherapies to treat cancer and cell-based therapeutics to treat neurological conditions associated with demyelination, reported enrollment and dosing of the first subject in the first-in-human Phase 1 clinical trial of AST-VAC2 in the United Kingdom (Press release, Asterias Biotherapeutics, JUN 12, 2018, View Source;date=June+12%2C+2018&title=Asterias+Biotherapeutics+Announces+First+Patient+Dosed+in+First-in-Human+Clinical+Study+of+Immunotherapy+AST-VAC2+in+Non-Small+Cell+Lung+Cancer [SID1234527282]). This initial clinical trial, which is being sponsored, managed and funded by Cancer Research UK, will examine the safety and tolerability of AST-VAC2 in non-small cell lung cancer (NSCLC) as the study’s primary endpoints. Secondary and tertiary endpoints of the study include evaluations of the immunogenicity of AST-VAC2 in NSCLC.
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"We are excited to have launched this clinical trial using AST-VAC2 for NSCLC," said the trial’s chief investigator Professor Christian Ottensmeier MD, PhD, FRCP, Professor of Experimental Medicine within Medicine at the University of Southampton. "The study will allow us to demonstrate the safety and immunogenicity of what I believe is a groundbreaking dendritic cell technology. The approach has the potential to redefine the way we use dendritic cell vaccines in the clinic and may be applicable to many cancer indications."
"We are thankful for Cancer Research UK’s sponsoring the clinical trial and look forward to advancing our immunotherapy strategy around this trial and the earlier Phase 2 trial of AST-VAC1 in Acute Myeloid Leukemia (AML)," said Michael Mulroy, President and Chief Executive Officer of Asterias. "AST-VAC2 is an allogeneic approach that has the potential to avoid many of the issues that autologous therapies face today. We are evaluating further development of AST-VAC2 as a monotherapy or in combination with other therapies in various cancer indications that may benefit from this therapy."
"We’re thrilled to be working with Asterias to bring this novel immunotherapy to patients with lung cancer. This cell therapy has massive potential," said Dr Nigel Blackburn, Cancer Research UK’s director of drug development. "Through our innovative Clinical Development Partnership scheme we have been able to offer our expertise in drug development and clinical trials management to drive this experimental treatment into the clinic."
AST-VAC2 is a "first-in-class" allogeneic cancer immunotherapy that is composed of mature dendritic cells which are designed to kill tumor cells by stimulating immune responses to telomerase, a tumor antigen expressed by over 85% of malignant tumor cells, but not by most normal healthy cells. AST-VAC2 is intended to be available for "on demand" patient use because it is produced from allogeneic pluripotent stem cells that can be manufactured in scale and then cryopreserved.
As currently designed, the clinical study will administer AST-VAC2 in up to 24 subjects with a specific immunological marker called HLA-A2, in one of two cohorts depending on the stage of each subject’s NSCLC. In the first cohort, up to 12 subjects with advanced disease will receive AST-VAC2, and will be followed for safety, immune responses to telomerase, and overall clinical survival. The second cohort will evaluate AST-VAC2 in up to 12 early-stage subjects who have had successful resection of their tumor with no evidence of metastasis, and each patient will be followed for safety, immune responses to telomerase, overall clinical survival and time to relapse. Both cohorts will also have a control group consisting of patients that meet all inclusion/exclusion criteria for the study but who do not have the HLA-A2 marker. The supply of AST-VAC2 to be used in this trial is being manufactured by Cancer Research UK’s Biotherapeutics Development Unit.
The partnership between Asterias and Cancer Research UK is being conducted under Cancer Research UK’s Clinical Development Partnerships (CDP) scheme, which allows the first clinical trial of AST-VAC2 to be initiated without significant Asterias resources being allocated to the trial and the manufacturing of the product. On completion of the clinical trial, Asterias will have an exclusive first option to acquire the data from the trial.
The results from the Phase 1 clinical trial sponsored and managed by Cancer Research UK could be used to support advanced clinical studies in one or more of the following areas:
Non-small cell lung cancer
Acute Myeloid Leukemia, leveraging the results of the previous AST-VAC1 trial in AML
Other indications showing high levels of telomerase activity and susceptibility to immunotherapy
In combination with check point or immune pathway inhibitors
In combination with additional antigens, including those arising from the exciting new field of tumor neoantigens
About AST-VAC2
AST-VAC2 is an innovative immunotherapy product that contains mature dendritic cells derived from pluripotent stem cells. These non-patient specific (allogeneic) AST-VAC2 cells are engineered to express a modified form of telomerase, a protein widely expressed in tumor cells, but rarely found in normal cells. The modified form of telomerase invokes enhanced stimulation of immune responses to the protein. Similar to an earlier, Asterias-sponsored, hematological cancer program which provided proof-of-concept data, the AST-VAC2 dendritic cells instruct the immune system to generate responses against telomerase and, through this mechanism, target tumor cells. AST-VAC2 is based on a specific mode of action that is complementary to and potentially synergistic with other immune therapies such as checkpoint inhibitors or other immune pathway inhibitors.
About Non-Small Cell Lung Cancer and the AST-VAC2 Trial
Lung cancer (both small cell and non-small cell) is the leading cause of cancer-related death, accounting for about one-quarter of all cancer deaths and more than colorectal, breast, and prostate cancers combined. Non-small cell lung cancer (NSCLC) accounts for about 80% to 85% of lung cancers, according to the American Cancer Society. The three main types of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. The American Cancer Society’s estimates for lung cancer in the United States for 2017 are: about 222,500 new cases of lung cancer, and about 155,870 deaths from lung cancer. Despite the large number of people afflicted by non-small cell lung cancer, patients remain vastly underserved due to a scarcity of effective treatments. According to statistics published by Cancer Research UK, the five year survival rate for lung cancer patients in England and Wales is less than 10%.
As currently designed, the AST-VAC2 Phase 1 clinical trial will enroll up to twenty-four subjects into one of two cohorts, depending on the stage of their non-small cell lung cancer. The first cohort will evaluate AST-VAC2 in up to 12 subjects with advanced non-small cell lung cancer. Subjects in this cohort, who carry the major histocompatibility gene, HLA-A2, will receive six weekly injections of AST-VAC2 and will be followed for safety, immune responses to telomerase and overall clinical survival. These survival results will be compared directly to a control group who meet all of the other inclusion/exclusion criteria but do not possess the HLA-A2 gene. Assuming safety is demonstrated in the first cohort, enrollment will advance to a second cohort. In the second cohort, early stage subjects who have had successful resection of their tumor with no evidence of metastasis will be enrolled. Up to 12 subjects in this second cohort who carry the major histocompatibility allele HLA-A2 will receive six, weekly injections of AST-VAC2 and will be followed for safety, immune responses to telomerase, overall clinical survival and time to relapse. These survival results will again be compared directly to a control group who meet all of the inclusion/exclusion criteria of cohort 2 but are not HLA-A2+. Subjects will be followed for one year for immune response to telomerase and for 2 years for the survival endpoints. Asterias and Cancer Research UK are exploring the combination of AST-VAC2 with an immune pathway inhibitor.