Immunomedics reports encouraging results from TF2 Phase I studies for colorectal cancer

Immunomedics, Inc. (Nasdaq:IMMU), a biopharmaceutical company focused on developing monoclonal antibodies to treat cancer and other serious diseases, today reported that TF2, a proprietary bispecific antibody, has shown selective tumor localization and minimal normal tissue retention in two early Phase I studies in patients with colorectal cancer.

Conducted at the Lombardi Comprehensive Cancer Center of Georgetown University, Washington, DC, the first study examined the pharmacokinetics, biodistribution, and tumor localization properties of TF2 in patients newly diagnosed with colorectal cancer. At the time of reporting, 2 patients were enrolled to receive TF2 labeled with iodine-131. The radiolabeled bispecific antibody was safely infused over 15 minutes and was cleared quickly from the blood.

TF2 belongs to a new generation of bispecific antibodies constructed using the Company's patented Dock-and-Lock (DNL) protein engineering platform technology, and is the first DNL product to enter human testing. Unlike conventional antibodies which attach to one receptor, bispecific antibodies have been engineered to contain an additional binding site. For TF2, it targets the carcinoembryonic antigen (CEA or CEACAM5) expressed by many human cancers, as well as a small radioisotope-carrying peptide.   

The creation of an additional binding site in bispecific antibodies is designed to be used in pretargeting methods.  Developed by the Company's majority-owned subsidiary, IBC Pharmaceuticals, Inc., pretargeting separates the delivery of radiation from the infusion of the tumor-targeting bispecific antibody. Only after the bispecific antibody has selectively localized to the target tumor and unbounded antibody has been removed from the rest of the body is the small radioisotope-carrying peptide injected.  The advantage of this approach is to improve the signal at the tumor relative to the background, or selectively increase the amount of therapeutic in the tumor.

Pretargeting with TF2 in patients with advanced colorectal cancer is also being evaluated at the Radboud University Medical Center, Nijmegen, The Netherlands. Patients are first given TF2 intravenously followed 5 days later with an Indium-111-labeled peptide for imaging. The cycle is repeated 7 days later for therapy using Lutetium-177 as the radionuclide. While these pretargeting conditions have yet to be optimized, initial imaging studies in 2 patients disclosed all known tumor sites. In addition, 1 patient received Lutetium-177 with no treatment-related toxicity. The study is continuing with a reduced interval and higher TF2 dose.

"Our initial clinical experience with TF2 has been encouraging," commented Cynthia L. Sullivan, President and CEO of Immunomedics. "These results are consistent with our preclinical experience with pretargeting, in which the delivery of imaging and therapeutic agents to diseased tissues compared to normal tissues is enhanced, potentially resulting in an increased effectiveness of these agents while lowering their undesirable side effects," Ms. Sullivan added.

No anti-TF2 antibodies were detected after 14 weeks in 3 patients. The fourth patient refused follow-up. Pretargeting with TF2 has been shown to produce tumor-specific PET imaging and prolonged survival in a human colorectal cancer model.