VB-111 in Combination With Nivolumab in People With Metastatic Colorectal Cancer (mCRC)

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Participation Requirements

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Background: Immune based approaches in GI cancers have unfortunately- with the notable exception of immune checkpoint inhibition in microsatellite instable (MSI-H) disease and gastric cancer-been largely unsuccessful. The reasons for this are unclear but no doubt relate to the fact that in advanced ...

Background: Immune based approaches in GI cancers have unfortunately- with the notable exception of immune checkpoint inhibition in microsatellite instable (MSI-H) disease and gastric cancer-been largely unsuccessful. The reasons for this are unclear but no doubt relate to the fact that in advanced disease GI cancer appears to be less immunogenic, as evidenced by the lack of infiltrating lymphocytes with advancing T stage as well as an immunosuppressive tumor micro environment. VB-111 is an anti-angiogenic agent comprising of a nonreplicating E1 deleted adenovirus type 5 which contains a modified murine preproendothelin (PPE) promoter and Fas-chimera transgene VB-111 has been tested and shows promise in glioblastoma, ovarian and thyroid tumors Nivolumab is a human monoclonal antibody directed against PD-1. The aim of this study is to study the effects of VB-111 in colorectal cancer (CRC) and to evaluate whether the antitumor immunity induced by VB-111 therapy can be enhanced by PD-1 inhibition. Objectives: To determine the safety and tolerability of VB-111 in combination with nivolumab in patients with refractory, metastatic CRC To determine Best Overall Response (BOR) (partial response (PR) + complete response (CR)) according to Response Evaluation Criteria (RECIST v1.1) of combined treatment of VB-111 and nivolumab in patients with refractory, metastatic CRC. Eligibility: Histopathological confirmation of colorectal cancer metastatic to the liver Patients must have progressed on > 2 lines of standard of care chemotherapy for colorectal cancer or been intolerant of chemotherapy or refused prior chemotherapy. Patients tumors must be documented to be microsatellite stable (MSS). Patients must have at least 1 focus of metastatic disease that is amenable to pre-and on-treatment biopsies and be willing to undergo this. All patients enrolled will be required to have measurable disease by RECIST v 1.1 criteria. Design: The proposed study is a phase II study of VB-111 in combination with immune checkpoint inhibition (nivolumab) in patients with metastatic CRC Treatment will be delivered in cycles consisting of 2 weeks with VB-111 given every 6 weeks and nivolumab given every 2-week until progression or unacceptable toxicity. Disease status evaluation will be done every 8 (+/- 1) weeks after the start of study therapy.

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