Bavarian Nordic and AZ combine cancer jab with durvalumab

The investigator-driven Phase I/II trial led by PI Dr. Michael Pishvaian will be conducted at Georgetown University. The Phase I part will evaluate safety of a combo of CV301, durvalumab and maintenance chemotherapy in patients with metastatic disease. In the Phase II part, the investigators will look for signs of preliminary efficacy as measured by progression-free survival (PFS), objective response rate (ORR), overall survival (OS), and disease control rate (DCR).

CV301 is a cancer prime/boost vaccine-based immunotherapeutic. Its prime, is comprised of the modified vaccinia Ankara-Bavarian Nordic (MVA-BN) vector. A fowlpox viral vector is used for the boosts. It encodes two tumor-associated antigens – carcinoembryonic antigen (CEA) and mucin-1 (MUC-1) -, plus TRICOM, a combination of the three immune-enhancing co-stimulatory molecules, B7-1, ICAM-1 and LFA-3. The administration of the vaccinia priming dose is followed by multiple boosting doses of the fowlpox vector.

The Phase I/II trial will begin with a 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 chemotherapy. The Phase 2 portion of the study will consist of two parallel trials, enrolling up to 26 patients for each disease setting.

"Combining a targeted cancer vaccine with a checkpoint inhibitor could result in a novel approach to fighting these diseases, as well as improved patient outcomes," said Pishvaian.

In theory, the CEA-MUC-1-TRICOM vaccine CV301 is expected to enhance presentation of CEA and MUC-1 to antigen-presenting cells (APCs) and to activate a cytotoxic T-lymphocyte (CTL) response against CEA- and MUC-1-expressing tumour cells. In preclinical trials, CV301 upregulated the expression of PD-L1 due to CTL-mediated tumor attack; when combined with a immune checkpoint inhibitor, thus, the antitumour effect should be increased.  

"With this trial, we are hopeful 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." said Paul Chaplin, President and Chief Executive Officer of Bavarian Nordic. Other CV301 combos in clinical testing include Merck & Co.’s pembrolizumab in lung cancer patients and Roche’s atezolizumab in bladder cancer patients.