One-for-all cancer treatment

PHILADELPHIA—Immunomedics, Inc., announced at the on-going annual meeting of the American Association for Cancer Research that, in a mid-stage clinical study, a multitude of patients with late stage solid cancers showed significant and durable tumor shrinkage after receiving treatments with sacituzumab govitecan, the company's lead antibody-directed chemotherapeutic agent. These include patients with metastatic triple-negative breast cancer whose cancers after treatment were no longer detected by computed tomography, a test commonly used to find and locate tumors, and to measure a patient's treatment response.

"All of these patients had failed many prior therapies for their cancers and were running out of options before being treated with sacituzumab govitecan," stated Dr. Alexander N. Starodub of the Indiana Health Center for Cancer Care, Goshen, Indiana, one of the principal investigators. "In this respect, we are very encouraged with the responses we are reporting at this year's annual meeting, especially in light of the fact that this novel agent is given to patients as a monotherapy, and not part of a drug cocktail. I believe sacituzumab govitecan has the potential to become a viable alternative for treating patients with advanced, metastatic solid cancers if these results are confirmed in a late-stage clinical trial," added Dr. Starodub.

At the time of analysis, a total of 184 patients with many different advanced, metastatic cancers were enrolled into the study. Dr. Starodub's oral presentation focused on interim responses from 130 patients having these four major solid cancer types: breast, lung, esophageal, and colorectal. For patients with triple-negative breast cancer, 26 percent showed objective response to sacituzumab govitecan, with two having a complete disappearance of their tumors, or complete response, and 10 showing a 30 percent or better tumor reduction, which qualified them as partial responders in accordance with the rules set by the Response Evaluation Criteria In Solid Tumors (RECIST 1.1). Including patients with responses between less than 30 percent tumor shrinkage and less than 20 percent tumor increase, which are considered stable disease, the disease control rate was 74 percent. At present, 21 of these patients are continuing therapy.

In lung cancer, the objective response rates were 32 percent and 30 percent for non-small-cell and small-cell lung cancers, respectively, and disease control rates were 74 percent and 55 percent, respectively. "These results compare very favorably to all other agents used in this disease and setting," commented Dr. Starodub. For the 18 patients with advanced cancer of the esophagus enrolled into the study, 16 were assessable for response, having an objective response rate of 13 percent and a disease control rate of 44 percent.

Also reported were results on 29 patients with colorectal cancer in early assessments of survival. The median length of time living without the disease getting worse from the beginning of their sacituzumab govitecan treatments was 3.9 months. The median length of survival from the start of treatment was 18.0 months. "These are very encouraging preliminary results for patients who had a median of 4 prior therapies for metastatic colorectal cancer, some as many as 8," remarked Dr. Starodub.

Commenting on these encouraging results, Ms. Cynthia L. Sullivan, president and CEO stated, "We are in discussion with FDA to formulate a registration pathway for sacituzumab govitecan to advance the agent to a Phase 3 registration trial. We are completing the enrollment of additional patients with triple-negative breast cancer, non-small and small-cell lung cancers. Our ultimate goal is to develop the full potential of this important and valuable asset for the benefits of cancer patients by advancing it with a corporate partner," Ms. Sullivan concluded.

Sacituzumab govitecan was created by the company for the therapy of solid cancers by selectively delivering the active anticancer drug, SN-38, to a target called TROP-2 that is produced in high amounts by cancer cells relative to normal tissues. These cancers include breast, lung, esophageal, stomach, colon, rectal, pancreatic, prostate, ovarian, urinary bladder, and uterine cancers.

SN-38 is formed in the body from irinotecan, a drug used in various combinations to treat patients with colorectal and other cancers. However, the process of converting irinotecan to the active SN-38 is inefficient, which lowers the efficacy of irinotecan. By attaching active SN-38 directly to a tumor-targeting antibody, as much as 136-times more SN-38 can be delivered directly to the tumor than when irinotecan is administered, without increasing the toxicity to the body at the same time.

Sacituzumab govitecan is well tolerated by patients. At the optimal doses of 8 and 10 mg/kg, only 7 percent of patients required having dosing delayed due to adverse reactions, while dose reductions were experienced in only 15-16 percent of patients. Grades 3 and 4 adverse events occurring in more than 5 percent of patients include fatigue (5 percent), neutropenia (24 percent), and anemia (6 percent). Irinotecan shows an increased incidence of severe diarrhea (38 percent), neutropenia (31 percent), and neutropenic fever (8 percent). Further, despite repeated injections, no patient produced any antibody against sacituzumab govitecan.

In addition to Dr. Starodub, other clinical investigators participated in this multicenter trial are Drs. Allyson J. Ocean, Linda T. Vahdat, Scott T. Tagawa, and Manish A. Shah, Weill Cornell Medical College, New York, NY; Dr. Aditya Bardia, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA; Drs. Michael J. Guarino and Gregory A. Masters, Helen F. Graham Cancer Center & Research Institute, Newark, DE; Drs. Wells A. Messersmith and Jennifer S. Diamond, University of Colorado Cancer Center, Aurora, CO; Drs. Jordan Berlin and Ingrid A. Mayer, Vanderbilt-Ingra Cancer Center, Nashville, TN; Dr. Vincent J. Picozzi, Virginia Mason Cancer Center, Seattle, WA; and Drs. Sajeve S. Thomas and Rebecca Moroose, UF Health Cancer Center-Orlando Health, Orlando, FL.

Immunomedics is a clinical-stage biopharmaceutical company developing monoclonal antibody-based products for the targeted treatment of cancer, autoimmune disorders and other serious diseases. Immunomedics' advanced proprietary technologies allow the Company to create humanized antibodies that can be used either alone in unlabeled or "naked" form, or conjugated with radioactive isotopes, chemotherapeutics, cytokines or toxins. Using these technologies, Immunomedics has built a pipeline of nine clinical-stage product candidates. Immunomedics has an ongoing collaboration with UCB, S.A. (UCB), to whom the Company licensed epratuzumab for the treatment of all non-cancer indications worldwide. UCB expects Phase 3 data in systemic lupus erythematosus in the first half of 2015. Immunomedics is exploring epratuzumab in oncology in collaboration with independent cancer study groups.

Immunomedics' most advanced candidate to which it retains worldwide rights for all indications is 90Y-clivatuzumab tetraxetan. The company initiated a Phase 3 registration trial in January 2014 in patients with advanced pancreatic cancer and expects topline data in mid-2016.

Immunomedics' portfolio of wholly owned product candidates also includes antibody-drug conjugates (ADCs) that are designed to deliver a specific payload of a chemotherapeutic directly to the tumor while reducing overall toxic effects that are usually found with conventional administration of these chemotherapeutic agents. Immunomedics' most advanced ADCs are sacituzumab govitecan (IMMU-132) and labetuzumab govitecan (IMMU-130), which are in Phase 2 trials for a number of solid tumors and metastatic colorectal cancer, respectively. Immunomedics also has a number of other product candidates that target solid tumors and hematologic malignancies, as well as other diseases, in various stages of clinical and pre-clinical development. These include bispecific antibodies targeting cancers and infectious diseases as T-cell redirecting immunotherapies, as well as bispecific antibodies for next-generation cancer and autoimmune disease therapies, created using its patented DOCK-AND-LOCK® protein conjugation technology.

The company believes that its portfolio of intellectual property, which includes approximately 267 active patents in the United States and more than 400 foreign patents, protects its product candidates and technologies. Immunomedics' strength in intellectual property has resulted in a top-8 ranking in the Biotechnology industry by the Patent Board for the 2014 fiscal year.