CV301 in Colorectal Cancer
In early 2018, two new additional studies have been introduced into the pipeline, both focused on colorectal and associated cancers, exploring two different indications and two different checkpoint inhibitors. These studies represent a novel step in the advancement of combinations therapies. While some patients respond to checkpoint inhibition as monotherapy in certain cancers, lung and bladders among them, colorectal cancers have not shown the same responsiveness. Many of these so-called “cold tumors” appear to lack an adequate T-cell response; this renders the checkpoint inhibitor class relatively inert. The combination of vaccine plus checkpoint in these types of indications could demonstrate the ability to take checkpoints where they cannot go alone.
The first study is a dual arm, open label Phase 1/2 study to evaluate the safety and clinical activity of the combination of AstraZeneca’s anti-PD-L1 durvalumab with CV301 in combination with maintenance chemotherapy for patients with metastatic colorectal (mCRC) or pancreatic cancer whose disease is stable on, or responding to first-line therapy for metastatic disease. Following a lead-in safety study, the Phase 2 portion of the study will consist of two parallel trials, enrolling up to 26 patients for each disease setting. The primary endpoint for both arms will be PFS, and there will be a minimal efficacy threshold to ensure adequate activity is seen prior to expanding enrolment. The study will be led by Dr. Michael Pishvaian, Assistant Professor in the Department of Hematology/Oncology at the Lombardi Comprehensive Cancer Center at Georgetown University Medical Center.
The second study is a Phase 2 trial that will enroll up to 74 patients with oligometastatic micro-satellite stable mCRC eligible for complete resection. Prior to surgical resection of their tumors, patients will be randomized to receive four cycles of either chemotherapy plus nivolumab or a combination of chemotherapy, nivolumab, and CV301. After resection, patients will then continue on with additional treatments in each arm. The multi-center study will be led by Darren R. Carpizo, MD, PhD, director of the Liver Cancer and Bile Duct Cancer Program at Rutgers Cancer Institute.