- Disease Education
SLE, commonly referred to as lupus, is a chronic and potentially fatal autoimmune disease with a variable and unpredictable course. Antibodies are generated against the body’s own nuclear proteins causing the immune system to attack its own cells and tissues resulting in inflammation, tissue and organ damage. This can occur in any part of the body, but most often targets the heart, joints, skin, lungs, blood vessels, liver, kidneys and nervous system.
Lupus is characterized by periods of flares, or exacerbations, interspersed with periods of improvement or remission. The Lupus Foundation of America estimated that between 1.5-2 million Americans have a form of lupus, 90 percent of whom are women. Symptoms and diagnosis occur most often between the ages of 15 and 45. In the U.S., lupus is more common in African Americans, Latinos, Asians, and Native Americans than in Caucasians.
Epratuzumab is currently in 2 multicenter, placebo-controlled, randomized, double-blind studies (EMBODY™ 1 and EMBODY™ 2), designed to evaluate its efficacy, safety, tolerability, and immunogenicity in patients with moderate to severe SLE.
For additional information about the EMBODY™ 1 trial, please see clinicaltrials.gov.
For additional information about the EMBODY™ 2 trial, please see clinicaltrials.gov.
In addition, we have received funding from the Peer Reviewed Medical Research Program of the Department of Defense to initiate a clinical trial evaluating milatuzumab, in a subcutaneous formulation, in patients with lupus clinicaltrials.gov.
Pancreatic cancer is often called a silent disease because it is difficult to detect and symptoms do not usually appear until the cancer has grown and often spread beyond the pancreas for quite some time. When symptoms do appear, they can be confused with other diseases. Depending on the stage and location of the cancer, surgery, chemotherapy and/or radiation therapy are used to treat this disease, but if the cancer has spread beyond the pancreas, therapy often is palliative, or focused on patient comfort.
According to the National Cancer Institute, an estimated 39,590 Americans will die from pancreatic cancer in 2014, about 7% of all cancer deaths, making the disease the fourth leading cause of cancer death in the United States. About 46,420 new cases in both sexes are expected in 2014.
The cause of pancreatic cancer is not known, but a small percentage of people develop the disease as a result of a genetic predisposition, which gives them a higher risk of developing this disease. Smoking is also considered to be a risk factor. There are typically no symptoms at the early stage, nor is there yet a reliable screening test for early detection. Pain is often felt in the upper abdomen and sometimes, the back, as one of the earliest symptoms and it is exacerbated after meals or when lying down. Other symptoms include loss of appetite, weight loss, nausea, and general fatigue. If the common bile duct is blocked by the tumor, jaundice appears.
Treatment options depend on stage and location of the cancer, age, and general health of the patient. Potentially curative surgeries are performed when the cancer has started in the head of the pancreas (near the bile duct), which can allow earlier detection when bile duct blockage produces jaundice. Palliative surgery is a type of surgery chosen when the tumor is too widespread and is done to relieve the symptoms or complications caused by the cancer. If the cancer has not spread beyond the pancreas, therapy can be successful, but it is rare to find pancreatic cancer in the early stages. In later stages, various forms of chemotherapy or combinations of radiation and chemotherapy are given to try to control the disease, and ultimately therapy strives to reduce pain. For all stages combined, the 1- and 5-year relative survival rates are 26% and 6%, respectively. For patients with advanced cancers, the median survival is 5.65 months.
Currently, the standard therapy for advanced pancreatic cancer is gemcitabine, alone or in combination with other chemotherapeutics. Gemcitabine became the standard treatment for advanced pancreatic cancer more than 14 years ago, after it was found to be superior to fluorouracil. Numerous Phase-III trials of newer cytotoxic drugs or biological agents in combination with gemcitabine have failed to demonstrate any survival improvement compared with gemcitabine alone except for erlotinib, which has been approved in combination with gemcitabine. The combination showed a median survival of 6.24 months compared with 5.91 months for gemcitabine alone, but the objective response rates were not significantly different; median one-year survival rates were 23% vs. 17%, respectively. The overall disease control rate (partial response and stable disease rates) was 57.5% for the combination and 49.2% for the gemcitabine arm, which was not statistically different. More recently, FDA approved Abraxane as a first-line treatment in combination with gemcitabine for patients with metastatic pancreatic cancer, after the combination showed a median overall survival of 8.5 months, compared with 6.7 months for gemcitabine alone.
Yttrium-90-labeled (90Y) clivatuzumab tetraxetan in combination with low-dose gemcitabine is currently being evaluated in a randomized, double-blind registration trial. The PANCRIT®-1 trial was designed to enroll approximately 440 patients with metastatic pancreatic cancer who had received at least two prior therapies. A majority of these patients will be recruited at clinical trial sites across the U.S., with additional sites in Canada, Europe and Israel participating. Eligible patients will be randomized 2 to 1 to the treatment arm of 3 doses of 90Y-clivatuzumab tetraxetan plus 4 doses of gemcitabine at 200 mg/m2 per cycle or placebo plus 200 mg/m2 gemcitabine. All patients will receive best supportive care. Treatments are administered during the initial 4 weeks of each 7-week cycle, and may be repeated up to a maximum of 6 cycles. More information on this trial can be accessed at clinicaltrials.gov.
Lung cancer is a malignant transformation of the lung tissue and is the deadliest form of cancer, claiming more lives than colorectal, prostate and breast cancers combined. Every year, lung cancer kills ~1.6 million people worldwide and ~160,000 people in the U.S, accounting for about 27% of all cancer deaths. In 2014, 224,210 new cases of lung cancer are expected in the U.S. Many of the symptoms of lung cancer (bone pain, fever, weight loss) are nonspecific and in the elderly, may be attributed to co-morbid illnesses. Furthermore, approximately 10% of the people with lung cancer do not demonstrate any symptoms at the time of diagnosis and in many patients, the cancer has already spread beyond the original site by the time they seek medical attention. The adrenal glands, liver, brain, and bone are the most common sites of metastasis from primary lung cancer.
There are two main types of lung cancer categorized by the size and appearance of the malignant cells seen by a histopathologist under a microscope - non-small-cell lung cancer or NSCLC (85%) and small-cell lung cancer or SCLC (roughly 15%). The latter of which is the more aggressive form. SCLC often starts in the bronchi near the center of the chest and spreads quickly to other parts of the body. Cigarette smoking is the biggest risk factor for SCLC.
Because the disease has often spread throughout the body by the time SCLC is diagnosed, standard treatments for patients with SCLC are chemotherapy and radiation therapy. Survival statistics vary depending on the stage of the cancer when it is diagnosed. According to the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database, 5-year survival rates by stage for patients with small cell lung cancer between 1988 and 2001 were 31%, 19%, 8% and 2% for stage I to IV, respectively.
IMMU-132 is currently in a Phase I/II clinical trial in patients with solid cancers, including SCLC. The antibody-drug conjugate has received orphan drug designation from FDA for the treatment of patients with SCLC.
Worldwide, breast cancer is the most frequently diagnosed cancer and the leading cause of death in women, accounting for 25% (1.67 million) of the total new cancer cases and 522,000 deaths per year (14% of total cancer deaths) in 2012. For women in the United States, breast cancer is the most prevalent cancer and the second most common cause of cancer death, after lung cancer, with 40,000 deaths estimated in 2014 (15% of all cancer deaths). Annual incidence of breast cancer in the U.S. was expected to be approximately 232,670 in 2014.
About 10-20% of breast cancers do not have the receptors for the hormones, estrogen and progesterone, or for the human epidermal growth factor (HER2). As such, they are known as triple-negative breast cancer, or TNBC. This type of breast cancer tends to occur more frequently in younger women, in African-American women, and in women who have BRCA1 mutations. In addition, it is often more aggressive and spreads more quickly than other types of breast cancer.
Standard hormonal therapies for breast cancers or drugs that target the HER2 receptor are ineffective against TNBC since the cancer lacks the necessary receptors. Chemotherapy and radiation therapy remain the standard for TNBC therapy. Although TNBC typically responded well to initial treatments, the cancer has high recurrence, metastatic, and mortality rates.
TNBC is one of the solid cancers included in the Phase I/II study of the antibody-drug conjugate, IMMU-132. For more information on this clinical trial, please refer to clinicaltrials.gov
Colorectal cancer is cancer that starts in either the colon or the rectum. Most cases of colorectal cancer are adenocarcinomas that begin as benign polyps from glands in the lining of the colon and rectum, which slowly develop into cancer. There is no single cause of colon cancer although the risk increases with age, a high fat diet, ulcerative colitis or Crohn’s disease, and a family or personal history of colorectal cancer.
Colorectal cancer remains a leading cause of cancer incidence and mortality worldwide. It is the third most commonly diagnosed cancer in men and the second in women, with over 1.2 million new cases and 608,700 deaths estimated to have occurred in 2008. In the U.S., with estimated 136,830 new cases and 50,310 deaths attributed to colorectal cancer in 2014, the disease ranked 4th by incidence following lung, breast and prostate cancers in both sexes, and second only to lung cancer in mortality.
Over the past 10 years, there have been important strides that have reduced the mortality of this disease primarily through more widespread screening that can catch the disease early before extensive spread. Treatment depends partly on the stage of the cancer and may include surgery, chemotherapy, radiation therapy and targeted therapy. However, progress, while real, has been modest. When the disease is diagnosed early and the cancer is confined to its primary site, the 5-year relative survival rate reaches 90%. The rate decreases to 69% when the cancer has spread to regional lymph nodes and 12% when it has metastasized. For all stages combined, the 5-year relative survival rate is 65%.
Our antibody-drug conjugate, IMMU-130, is in a Phase I/II study in patients with metastatic colorectal cancer. Information on this clinical trial can be obtained from clinicaltrials.gov.