The new trial evaluates the combination therapy of CV301 and durvalumab in metastatic colorectal and pancreatic cancers.

The first patient has been dosed in a clinical study evaluating CV301, the company’s targeted immunotherapy candidate, and durvalumab, AstraZeneca’s PD-L1 inhibitor, in combination with maintenance chemotherapy for patients with metastatic colorectal or pancreatic cancers.

Pre-clinical data

Bavarian Nordic’s CV301 targets tumor-associated antigens, CEA and MUC1, which are overexpressed on multiple solid tumors, including colorectal and pancreatic cancers. Preclinical data has shown that vaccination resulted in the induction of tumor specific T-cells that infiltrated the tumor resulting in the upregulation of PD-L1 on tumor cells. The upregulation of PD-L1 is a marker indicating the tumor is under attack from T-cells, presenting an opportunity for a greater response in patients who might otherwise not benefit from treatment with a checkpoint inhibitor alone.

Trial design

CV301 is administered in a manner designed to generate a potent and durable T-cell response. Patients receive an enhanced priming regimen of the highly attenuated, non-replicating vaccinia virus MVA-BN-CV301 in 4 different injection sites on days 1 and 29, followed by boosters of the recombinant fowlpox virus FPV-CV301 at tapering intervals during the course of the treatment with durvalumab and maintenance chemotherapy.

The investigator-sponsored trial is being led by Dr. Michael Pishvaian, Associate Professor in the Department of Hematology/Oncology at the Lombardi Comprehensive Cancer Center at Georgetown University Medical Center in Washington, D.C., with material support from Bavarian Nordic and AstraZeneca. The clinical trial is being conducted at several other top cancer centers including the Mayo Clinic, Indiana University and Emory University.

The trial will begin with a small lead-in study to determine the safety and tolerability of the combination, as well as the recommended Phase 2 dose of durvalumab in combination with CV301 and maintenance chemotherapy. The Phase 2 portion of the study will consist of two parallel trials, enrolling up to 26 patients with metastatic disease for each disease setting. The primary endpoint for both arms of the study will be progression-free survival (PFS) with multiple secondary endpoints, including objective response rate (ORR), overall survival (OS), and disease control rate (DCR).

A novel approach

“We are excited to continue demonstrating CV301’s potential in multiple cancers and combinations, particularly in a treatment setting in which checkpoint inhibition alone has yet to show significant benefit. The combination of a targeted cancer vaccine with a checkpoint inhibitor could result in a novel approach to fighting colorectal and pancreatic cancers, which are among the most difficult-to-treat malignancies to date,” said Paul Chaplin, President and Chief Executive Officer of Bavarian Nordic.