Bavarian Nordic today said it will partner with AstraZeneca in a Phase I/II clinical trial assessing the combination of its immunotherapy candidate CV301 and AstraZeneca’s marketed treatment Imfinzi™ (durvalumab) plus maintenance chemotherapy in patients with metastatic colorectal or pancreatic cancers.

The companies agreed to contribute clinical trial material and funding for the planned Phase I/II study, which is being sponsored by Georgetown University. The trial will be led by Michael Pishvaian, M.D., Ph.D., assistant professor in the department of hematology/oncology at Georgetown University Medical Center’s Lombardi Comprehensive Cancer Center.

The value of the clinical collaboration was not disclosed.

The trial (NCT03376659) will begin with a lead-in study to determine the safety and tolerability of the combination, as well as the recommended Phase II dose of Imfinzi in combination with CV301 and chemotherapy. The Phase II 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 of the study will be progression-free survival with multiple secondary endpoints, including objective response rate, overall survival, and disease control rate, Bavarian Nordic said.

“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,” Bavarian Nordic president and CEO Paul Chaplin, Ph.D., said in a statement.


Third Combo Study with Checkpoint Inhibitor

Bavarian Nordic said the trial will mark the third evaluation of CV301 in combination with a checkpoint inhibitor for oncology indications. The other two combination trials involving CV301 are with Merck & Co.’s programmed cell death protein 1 (PD-1) inhibitor Keytruda® (pembrolizumab) in non-small-cell lung cancer (NSCLC) and Roche’s Tecentriq® (atezolizumab) in bladder cancer.

CV301 is a poxvirus-based prime/boost cancer vaccine designed to target carcinoembryonic antigen (CEA) and mucin1 protein (MUC1), two tumor-associated antigens that are over-expressed in multiple solid tumors, including lung, bladder, colorectal, and pancreatic cancers. CV301 incorporates a modified version of vaccinia virus (MVA-BN®, or Modified Vaccinia Ankara, a proprietary technology of Bavarian Nordic) as a priming dose, followed by multiple fowlpox boosts, and encodes the TRICOM costimulatory molecules.

In preclinical studies, CV301 has shown its ability to upregulate programmed death ligand 1 (PD-L1) by mounting an immune response against a tumor target. Such upregulation indicates that a tumor is under attack from T cells—which according to the company presents an opportunity for a greater response in patients who might otherwise not benefit from treatment with a checkpoint inhibitor alone.

Imfinzi is a PD-L1 inhibitor initially approved by the FDA last year for locally advanced or metastatic urothelial carcinoma patients who have disease progression either during or following platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

On February 16, Imfinzi won additional FDA approval for unresectable, stage III NSCLC whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.