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CV301

Immunotherapy candidate for multiple cancers

PHASE 2


CV301 is a cancer immunotherapy candidate, originally developed by the National Cancer Institue. CV301 targets two tumor-associated antigens, CEA and MUC-1, that are over-expressed in major cancer types, including lung, bladder and colorectal cancer. Similar to PROSTVAC, CV301 uses a vaccinia prime, followed by multiple fowlpox boosts, and encodes the TRICOM costimulatory molecules.

CV301 has been tested in 6 ongoing or completed NCI-sponsored clinical trials in various cancers, and more than 300 patients have been treated with the product candidate.

We have generated a new and improved vaccine construct, in which the vaccinia primer has been replaced with MVA-BN. This new version will be employed in the future development of CV301, focusing on combination treatments with checkpoint inhibitors.

Checkpoint inhibitors have shown promising efficacy as single agent treatments in clinical trials in various cancers. However, the majority of cancer patients are not responding to checkpoint inhibitors, and this appears to be related to low or negative expression of programmed death-ligand 1, or PD-L1, a transmembrane protein that has been speculated to play a major role in suppressing the immune system. Low PD-L1 expression is widely defined as <5% PD-L1. This limited response is believed to be due in part to individual patients lacking an immune response to attack the tumors.

We believe CV301 equips the immune system with the ability to seek out and destroy these tumors. Preclinical data shows the ability to upregulate PD-L1 by mounting an immune response against a tumor target. 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.

While non-small cell lung cancer (NSCLC) represents the first clinical target, we plan to initiate no less than three separate randomized, placebo-controlled Phase 2 trials in NSCLC, bladder cancer and colorectal cancer, in combination with assorted checkpoint inhibitors. These studies will evaluate the efficacy of the vaccine and the checkpoint inhibitor to determine what, if any, synergy can be seen in combination. As it pertains to NSCLC, overall survival (OS) will be the primary endpoint for the study, but additional secondary endpoints such as progression free survival (PFS) and overall response rate (ORR), will be investigated. These secondary endpoints may provide a signal of activity prior to an OS endpoint.

CEA and MUC-1 overexpression in selected cancers

  CEA+ MUC-1+
Lung cancer 70% 80%
Bladder cancer 60% - 75% >90%
Colorectal cancer >90% >90%
Breast cancer 50% >90%
Pancreatic cancer >95% >95%