On October, 2017 Seattle Genetics, Inc. (NASDAQ: SGEN) reported two clinical collaboration agreements for the evaluation of SGN-LIV1A in patients with triple negative breast cancer (TNBC). SGN-LIV1A is an investigational antibody-drug conjugate (ADC) that targets the cell surface protein LIV-1, which is expressed on multiple solid tumors including breast, prostate, melanoma, ovarian, and cervical cancers (Press release, Seattle Genetics, OCT 11, 2017, View Source [SID1234520849]). The ADC will be tested in combination with KEYTRUDA (pembrolizumab), an anti-PD-1 therapy marketed by Merck (known as MSD outside the United States and Canada), in a phase 1b/2 clinical trial as first line treatment for locally advanced and metastatic TNBC. SGN-LIV1A in combination with standard chemotherapy will also be evaluated as neoadjuvant treatment in the phase 2 I-SPY 2 TRIAL for newly diagnosed Stage 2 or 3 human epidermal growth factor receptor 2 (HER2) negative breast cancer, sponsored by Quantum Leap Health Care Collaborative (Quantum Leap). This cancer subgroup accounts for up to 85 percent of breast cancer and includes TNBC.
“Our new collaborations expand the clinical investigation of SGN-LIV1A by evaluating this ADC in earlier lines of treatment for TNBC, including the frontline setting in combination with pembrolizumab. In the neoadjuvant setting, SGN-LIV1A has the potential to benefit a broader population of women with breast cancer,” said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. “Breast cancer is the most common cancer in women, excluding some forms of skin cancer, in the United States. Of the over 250,000 new cases expected to be diagnosed in the US this year, about 15 to 20 percent are TNBC, which is very aggressive and associated with poor patient outcomes. With four clinical studies underway or planned for SGN-LIV1A in TNBC, we are advancing our goal to improve the health of women with this devastating disease.”
SGN-LIV1A administered in combination with Merck’s pembrolizumab will be evaluated in a phase 1b/2 clinical study in patients with locally advanced or metastatic TNBC. This single arm, open label multicenter study is anticipated to enroll up to 72 patients. Under the terms of the collaboration agreement with Merck, Seattle Genetics will hold the IND for the study and retain global development and commercialization rights to SGN-LIV1A.
SGN-LIV1A followed by standard chemotherapy (doxorubicin and cyclophosphamide) will be evaluated as a neoadjuvant treatment (prior to surgery) for women with newly diagnosed, locally advanced Stage 2 or 3 HER2-negative breast cancer in the I-SPY 2 TRIAL. This standing phase 2 randomized, controlled multicenter trial is anticipated to enroll up to 75 patients in the SGN-LIV1A treatment arm. With TNBC and other aggressive cancers in mind, the I-SPY 2 TRIAL was designed to rapidly screen promising experimental treatments and identify those most effective in specific patient subgroups based on molecular characteristics (biomarker signatures). The trial is a unique collaborative effort by a consortium that includes the Food and Drug Administration (FDA), industry, patient advocates, philanthropic sponsors and clinicians from 20 major U.S cancer research centers. Under the terms of the collaboration agreement, Quantum Leap is the trial sponsor and will manage the study operations. Seattle Genetics will retain global development and commercialization rights to SGN-LIV1A.
Four clinical studies are underway or planned for SGN-LIV1A in breast cancer, with a focus on TNBC. In addition to the aforementioned trials, SGN-LIV1A monotherapy is being evaluated in an ongoing phase 1 trial for patients with metastatic breast cancer, including patients heavily pre-treated for TNBC. A phase 1b/2 trial is planned to evaluate SGN-LIV1A as part of a combination regimen as second line treatment for patients with metastatic TNBC who have not been previously treated with immunotherapy.
About Breast Cancer
Breast cancer is a cancer which forms in breast tissue. Metastatic breast cancer occurs when the cancer has spread to other parts of the body. While most new diagnoses of breast cancer are made at an early stage, approximately one-third of these patients will eventually develop recurrent or metastatic disease. Breast cancers are commonly categorized by the expression (or lack thereof) of three key proteins, which serve as targets for therapeutics. These include the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Triple-negative breast cancer (TNBC) lacks all three proteins and HR+/HER2- breast cancer expresses one or both hormone receptors (HR) but not HER2. According to the World Health Organization, breast cancer is the most common cancer in women worldwide with an estimated 1.67 million new cancer cases diagnosed in 2012. In addition, breast cancer ranks as the fifth cause of death from cancer overall globally. New treatment approaches are needed to improve outcomes for breast cancer patients, particularly for those with TNBC where there are currently no available targeted therapies.
About SGN-LIV1A
SGN-LIV1A is a novel investigational ADC targeted to LIV-1 protein utilizing Seattle Genetics’ proprietary ADC technology. LIV-1 is expressed by most metastatic breast cancers. It has also been detected in a number of other cancers, including melanoma, prostate, ovarian, and cervical cancers. SGN-LIV1A consists of a LIV-1-targeted monoclonal antibody linked to a potent microtubule-disrupting agent, monomethyl auristatin E (MMAE) by a protease-cleavable linker, using the same technology as ADCETRIS (brentuximab vedotin). It is designed to bind to LIV-1 on cancer cells and release the cell-killing agent into target cells upon internalization. SGN-LIV1A may also cause antitumor activity through other mechanisms, including activation of an immune response.