Welcome to your Update from the Clinic for the month of September. OncoSec Medical released some initial data from its Phase 1/2 study investigating ImmunoPulse IL-12 DNA in a rare skin cancer. Pluristem and the National Institute of Allergy and Infectious Diseases (NIAID) have agreed upon a trial design for Pluristem’s Phase 2 study investigating PLX-R18 cells in acute radiation syndrome. Aduro announced a clinical trial agreement (CTA) for the investigation of a combination therapy in patients with ovarian cancer. Lion Biotechnologies released positive data from an ongoing study of its TIL therapy in patients with metastatic melanoma.
OncoSec Medical (ONSC) is targeting a rare form of skin cancer, known as Merkel Cell Carcinoma, with its ImmunoPulseTM IL-12 technology (IL-12 DNA plasmid injected intratumorally and electroporated – through an electric shock – in situ). Initial Phase 2 efficacy data reported this past month quite clearly demonstrates the cytokine can both promote tumour immunogenicity (the ability of a particular substance to provoke an immune response in the body of a human or animal) and anti-tumour immune responses. Tumour biopsies from electroporated lesions in 79 per cent of patients showed expression of IL-12, indicating that DNA was successfully transferred into cells (in the form of a plasmid). The intriguing finding was that 30 per cent of patients showed regression in at least one distant, non-electroporated lesion, which demonstrates the systemic impact the technology can deliver against cancer cells spread throughout the body.
Ziopharm (ZIOP), another company developing an in situ IL-12 cell therapy, and the only company developing an IL-12 therapy that can be controlled through administration of a small molecule (Ad-RTS-hIL-12), presented additional clinical data at the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference. In two open-label Phase 2 studies that collectively enrolled 38 patients with either metastatic breast cancer or advanced melanoma, clinicians showed that the adenovirus-based therapy activated expression of a number of the downstream cytokines of IL-12: IFNg, IP-10, and IL-10. Further to this, introduction of the adenovirus was linked to a significant increase in tumour infiltrating lymphocytes (TILs) found in both local and systemic tumours.
Pluristem (PSTM) has been working on a solution for acute radiation syndrome (ARS) derived from the placenta (PLX-R18). The company reported this past month that, in collaboration with NIAID, it has finalized a development plan that will lead to a pivotal study in animals that will provide the data necessary for marketing of PLX-R18. Under the FDA’s Animal Rule, where human studies are not feasible or ethical, a study conducted using a large animal model is sufficient. The technology is largely being developed for its utility in treating humans following a nuclear catastrophe. To date, two studies have been completed in mouse models showing that PLX-R18 had a significant impact on white and red blood cells recovery, and 30 day survival in mice exposed to lethal doses of radiation.
Aduro Biotech (ADRO), which recently acquired antibody discovery company BioNovion, announced a CTA to investigate the preliminary efficacy of its engineered Listeria platform (CRS-207) along with Incyte’s epacadostat (an IDO1 inhibitor) in patients with ovarian cancer. The goal of the study, like any combinatorial approach, will be to see whether the therapies exhibit synergistic effects when administered together. Epacadostat has been shown to disrupt the tumour microenvironment (an approach venture capitalists like at the moment) increasing the immunogenicity of cancer cells, while CDS-207 increases immune cells’ capability of seeking and attacking cancer cells that express the protein mesothelin (broadly upregulated in a number of cancers). Incyte has also partnered with Merck, on epacadostat, to investigate its clinical utility in combination with Merck’s Keytruda (pembrolizumab).
Lion Biotechnologies (LION) stands alone in the field of cell-based immunotherapy as the only company to have a strong pipeline of TIL candidates (expanded from one to five different candidates this month in a deal with the National Cancer Institute). Dr. Steven Rosenberg, Chief of Surgery at the National Cancer Institute, reported positive results from a Phase 2 study investigating TILs in patients with advanced metastatic melanoma, which show the therapy can induce durable complete responses (full remission) in patients. The study was divided into two equal arms, one where patients received chemotherapy, and a second where patients received whole body irradiation, in addition to chemotherapy. A combination of autologous TILs (harvested from a patient’s own tumour sample) and IL-2 administration produced an overall response rate of 54 per cent, while 23 per cent of patients had durable complete responses. The company is also enrolling patients in a single-arm, multi-centre, Phase 2 study investigating LN-144 (TILs) in 20 patients with refractory metastatic melanoma that have received at least one systemic therapy. The objective of the study is to evaluate the safety and efficacy of TILs manufactured using Lion’s central manufacturing process.
When reporting outcomes, durability – or the length of time a complete response lasts – is essential in determining the quality of treatment and it is something that payers look for when evaluating clinical data. LION has taken the right approach by emphasizing this aspect of its clinical data. Many companies release complete remission results, but omit discussion of the durability of these responses. The Center for Medicare and Medicaid Services (CMS) will look for this data when making coverage determinations at the local or national level. Published studies in peer-reviewed journals are also frequently sought and reviewed when determining coverage. Clinical data generation need to be performed through the lens of both the regulator and payer; the payer is often more demanding, and will require data above and beyond what the regulatory agency requires.
Disclaimer: “Update from the Clinic” is a blog post generated by news flow from public regenerative medicine (RM) companies around the globe. As CCRM has public RM companies in its industry consortium, and the number of such companies is relatively limited on a global scale, Mark Curtis will sometimes include CCRM consortium members in his review. This blog post is provided for general information only and nothing contained in the material constitutes a recommendation for the purchase or sale of any security. The author is not a shareholder of any public RM company. To see a list of CCRM’s industry consortium members, please visit http://ccrm.ca/industry-consortium