Evaluation of Safety, Immunogenicity, and Preliminary Efficacy of PolyPEPI1018 Vaccine with CDx in Subjects with Metastatic Colorectal Cancer

Topic Area This project falls under the Fiscal Year 2019 (FY19) Peer Reviewed Cancer Research Program (PRCRP) Topic Area of: Colorectal Cancer. This project falls under the FY19 PRCRP Military Health Focus Area of: Gaps in cancer prevention, early detection/diagnosis, prognosis, treatment, and/or survivorship that may impact mission readiness and the health and well-being of military members, Veterans, their beneficiaries, and the general public. The proposal describes development of a therapeutic cancer vaccine against metastatic colorectal cancer (mCRC), together with a companion diagnostic device for the selection of likely responders, which has the potential to offer a treatment solution to patients who have already exhausted two types of cancer therapy. Rationale Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide. Global incidence was 1.8 million new cases and almost 861,000 deaths in 2018, according to the World Health Organization. CRC is the third most common cancer and the third leading cause of cancer death in men and women in the United States. Chemotherapy of various types represents the standard treatment approach for patients with mCRC, but the treatment often fails to stop the cancer's progression. Consequently, many patients must undergo two and even three different approaches as part of the efforts to treat them successfully. Patients undergoing third line therapy have limited therapeutic options and suffer reduced quality of life from the few treatments that are available. Immunotherapy is an attractive treatment option since it is more tolerable than conventional chemotherapy, with potential long-lasting responses. However, most mCRC patients fail to respond to immune-based treatment. We developed the PolyPEPI1018 vaccine, which is a novel, patient-tailored immunotherapy for mCRC patients. In contrast to existing approaches (checkpoint inhibitors), PolyPEPI1018 not only re-activates existing immune responses but also induces new immune responses against specific tumor antigens, thereby boosting the immune system to attack cells without immune-related toxicities. Besides the vaccine, a companion diagnostic test to identify patients who would likely benefit from the vaccine treatment is also being developed. Thus our research development represents a powerful next-generation tool in cancer treatment and patient care. Objective The proposed Clinical Trial aims to investigate the safety, tolerability, immunogenicity, and efficacy of PolyPEPI1018 vaccine in metastatic colorectal cancer patients after two types of chemotherapy treatment. Offering a safe, non-toxic and primarily effective vaccine treatment to patients who have already progressed after two lines of systemic therapy would greatly benefit them. Our aim with the present study is to show that our vaccine stops the continued progress of the cancer and enables patients in this advanced stage of cancer to enjoy longer and better quality of life without a further chemotherapy regimen. Impact & Applicability This approach could serve as the basis for the design of efficient off-the-shelf and personalized cancer vaccines for mCRC patients who have exhausted standard forms of treatment, as well as for patients in early stages to avoid the devastating side effects and poor outcomes of chemotherapy. Promising Outcomes for a Military Health Focus Area The US Department of Veterans Affairs (VA) treats approximately 3% of all colorectal cancer cases in the US each year, including approximately 6% of cases among men. Additionally, Veterans receiving care in the VA healthcare system are, on average, older and often have a higher comorbidity burden relative to the general US population. Veterans may also engage in health behaviors, including smoking and poor dietary habits, that impact cancer risk. Therefore, there is an urgent need for novel colorectal cancer treatments for the military population.