Evaluation of TLR agonist Z-007 in dogs with cancer

While significant improvements in immune based cancer treatments have been made, stimulating an effective immune response to most cancers remains a challenge. The purpose of this study is to evaluate a new agent called Z-007 that works by stimulating immune cells by binding key proteins called Toll Like Receptors (TLRs). These TLRs are responsible for alerting the immune system and helping to create inflammation, that then activates other cells that are important for killing tumor cells. Preliminary unpublished studies of Z-007 have demonstrated good activity in mouse models of cancer when Z-007 is given by either intravenous or intratumoral injection. Additionally, a previous study was completed in pet dogs with a variety of cancers to provide preliminary data on safety and effectiveness of Z-007. Of the 7 dogs treated, 3 had greater than 30% shrinkage of their tumors, and another two had unexpectedly long durations of stable disease. The Z-007 was well tolerated by all dogs, with mild nausea post treatment being the only side effect noted. In the current study, dogs with solid tumors (carcinomas, sarcomas, melanoma) will be treated with Z-007 by either intratumoral or intravenous injection, and we will follow them to determine response to treatment to identify the most effective dose and route for administration. We will also collect tumor and blood samples to understand how Z-007 alters the local and systemic immune system, with the goal of identifying key biomarkers associated with response to treatment. Together, these studies will provide important data that will help improve the use of Z-007 in dogs with cancer.

Inclusion Criteria

Pet dogs will be eligible for enrollment if they have: a solid tumor (carcinoma, sarcoma) between 2-7 cm in size that is amenable to repeat biopsy; no significant underlying co-morbidities (kidney, heart, liver disease); no abnormalities in cell or platelet counts on a complete blood count; no prior treatments with immunotherapy agents; and no history of autoimmune disease. Dogs may not have received any previous treatment for their cancer, or may have failed standard cancer treatments (surgery, radiation therapy, chemotherapy). While the presence of metastasis is not an exclusion factor, dogs must have a life expectancy of at least 8 weeks. Dogs must also be at least 7 kg in size.

Exclusion Criteria

• Significant underlying heart, kidney or liver disease
• Tumors less than 2 cm and greater than 7 cm in size will be excluded

Client Benefits

For participation in the this clinical study, all costs associated with treatment of your dog’s cancer with Z-007 will be covered up to Day 63 of the study. The study will cover treatment for side effects related to the Z-007 administration and biopsy (i.e., vomiting, diarrhea, infection of the biopsy site) but it will not cover treatment of conditions unrelated to the study, such as bladder infection, ear infection, etc.

If you choose to continue the Z-007 after Day 63, you will be responsible for the costs associated with the study visits and routine bloodwork.

Sample or Data Requirements

To be eligible for enrollment, your dog must be at least 7 kg in size, have a solid tumor (carcinoma, sarcoma, melanoma) between 2-7 cm in size that can be biopsied and/or have tumor spread (metastasis) to the lungs. Your dog must have no significant kidney, heart, or liver disease and no abnormalities on a complete blood count. Your dog must not have received any prior treatments with immune therapy, and must not have had an autoimmune disease. Your dog may have been previously treated with surgery, chemotherapy and/or radiation therapy, or may have be untreated for their cancer. Dogs may have not received any previous treatment for their cancer, or may have failed standard cancer treatments (surgery, radiation therapy, chemotherapy). Baseline screening tests include routine bloodwork (complete blood count, chemistry panel), a urine exam, and chest x-rays. Once enrolled in the study, your dog will have blood collected for the study (15 mls, approximately 1 tablespoon) and a tumor biopsy will be performed under sedation (this is not general anesthesia). Your dog will then have the Z-007 given by either intravenous or intratumoral injection once per week for 4 weeks (Days 0, 7, 14, 21); on Day 14, study blood will be collected again. On Day 28 of the study, the routine bloodwork and chest x-rays (if applicable) will be repeated, as well as the study blood collection and a second tumor biopsy. If your dog is doing well with either stable disease or a complete/partial shrinkage of tumor, Z-007 will be administered again on D35 and D49. The routine bloodwork, chest x-rays, study blood collection and tumor biopsy will then be repeated on D63. If your dog continues to do well, then they may recieve the Z-007 every 2 weeks for up to 6 months on a compassionate use basis. The Study Calendar on the last page of this consent provides an overview of all the required study visit and associated study activities.