Raven Initiates Clinical Trial Of RAV12 Therapeutic Antibody For Adenocarcinomas Treatment
Raven biotechnologies is continuing to enroll new patients in the maximum tolerated dose cohort expansion segment of its Phase 1/2a trial for patients with cancers of the gastrointestinal tract that express the RAAG12 antigen.
RAAG12 is a glycotope (sugar structure) that is widely found on the surface of tumor cells of many kinds of cancer, particularly cancers of the gastrointestinal tract (adenocarcinomas of gastroesophageal, pancreatic and colorectal origin). RAV12, Raven's lead clinical monoclonal antibody drug candidate, targets the RAAG12 antigen.
This segment of the trial will yield additional information about the safety of the drug and define the pharmacokinetics of the antibody.
The appropriate dose and schedule of RAV12 was chosen in a dose-escalation segment of the Phase 1/2a trial that involved 33 patients. This trial revealed that a fractionated dosing regimen provided an improved safety profile for the antibody. Raven is now enrolling patients in a second segment of the trial in which all patients are receiving the recommended dose and schedule of drug. Information from the Phase 1/2a trial will be supporting the dosing in a Phase 2 study in pancreatic cancer, the next clinical trial scheduled for RAV12.
The trial is being conducted at five institutions in the United States: The Sarah Cannon Cancer Center in Nashville, TN; The Fox Chase Cancer Center in Philadelphia, PA; Premiere Oncology in Santa Monica, CA; Georgetown University Medical Center in Washington, DC; and The University of Miami Medical Center in Miami, FL.
RAV12 is a novel, chimeric monoclonal antibody that is directed against a primate-specific glycotope (sugar structure) that is widely displayed on the surfaces of tumor cells, particularly those of gastrointestinal origin (gastroesophageal, pancreatic, and colorectal cancers). Preclinical studies have demonstrated that RAV12 may kill tumor cells in a number of ways: first, the antibody is directly cytotoxic to a human colon cancer cell line in vitro through induction of oncotic cell death, a form of cell death characterized by cell and organelle swelling and loss of membrane integrity; second, the antibody mediates antibody-dependent cellular cytotoxicity; third, the antibody mediates complement dependent cell killing; and finally, the antibody alters cellular signaling required for cell survival. RAV12 is highly efficacious in human colon, gastric, and pancreatic tumor xenograft models in vivo and has been found to be well tolerated in repeat dose primate toxicology studies.
About GI Cancers
Adenocarcinomas are malignant tumors of the epithelial cells that line glands or viscera. They typically spread by way of the circulatory or lymphatic systems and are poorly treated after metastatic spread. More than 90 percent of colon, stomach and pancreatic tumor specimens express the RAV12 defined antigen, RAAG12. Adenocarcinomas arising elsewhere, such as breast, endometrial, ovarian, lung and prostate, display the antigen at lower frequency.