First Clinical Data Presentation of SGN-LIV1A Demonstrates Antitumor Activity and Well-Tolerated Safety Profile in Patients with Triple Negative Metastatic Breast Cancer
SAN ANTONIO, TX, USA I December 10, 2015 I Seattle Genetics, Inc. (Nasdaq: SGEN) today presented data from an ongoing phase 1 clinical trial evaluating SGN-LIV1A, an antibody-drug conjugate (ADC) in development for patients with LIV-1-expressing metastatic breast cancer (MBC), at the 38th San Antonio Breast Cancer Symposium (SABCS) taking place in San Antonio, Texas, December 8-12, 2015. SGN-LIV1A consists of a humanized anti-LIV-1 monoclonal antibody (mAb) and the microtubule-disrupting agent monomethyl auristatin E (MMAE), utilizing a protease-cleavable linker. ADCs are monoclonal antibodies that are designed to selectively deliver cytotoxic agents to tumor cells. This approach is intended to spare non-targeted cells and thus reduce many of the toxic effects of traditional chemotherapy while enhancing antitumor activity.
“While there have been important advances in the treatment of breast cancer, there remains a significant unmet medical need for improved therapies, particularly in the metastatic setting where there are no curative therapies and fewer than 25 percent of patients survive five years,” said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. “The data presented at SABCS on SGN-LIV1A demonstrate early antitumor activity in heavily pretreated patients, notably among patients with triple negative disease, at generally well-tolerated doses. We are currently enrolling patients with triple negative breast cancer, a subtype for which there are no approved targeted treatments available, to further assess the activity of SGN-LIV1A in a disease-specific cohort.”
Interim Analysis of a Phase 1 Study of the Antibody-Drug Conjugate SGN-LIV1A in Patients with Metastatic Breast Cancer (Abstract #638, Poster Session 3 at 5:00 – 7:00 p.m. CT on Thursday, December 10, 2015)
LIV-1 is highly expressed in breast cancer, and is present in 96 percent of 237 MBC samples screened to date. Moderate-to-high expression was observed in 88 percent of hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancers and in 79 percent of triple negative breast cancers (TNBC). The ongoing phase 1, open-label, dose-escalation trial is evaluating the safety, tolerability, antitumor activity, pharmacokinetics and maximum tolerated dose (MTD) of SGN-LIV1A monotherapy administered every three weeks in patients with LIV1-expressing MBC.
Data were reported from 27 patients with LIV-1-expressing MBC, of whom 18 were HR+/HER2- and nine were TNBC. The median age of patients was 57 years and the median number of prior systemic metastatic cytotoxic therapies was four. Key findings presented by Dr. Andres Forero, from the University of Alabama at Birmingham, included:
- Of the 25 efficacy-evaluable patients, the objective response rate (ORR) was 12 percent, the disease control rate was 64 percent and the clinical benefit rate (CBR) was 24 percent. Disease control rate is defined as patients achieving a complete response (CR), partial response (PR) or stable disease (SD). CBR is defined as patients achieving CR, PR or SD lasting at least six months.
- Among the eight patients with TNBC, the ORR was 38 percent and CBR was 63 percent.
- At the time of data analysis, early estimates of median progression-free survival (PFS) for all patients was 11 weeks, with an estimated median PFS in TNBC patients of 18.4 weeks and an estimated median PFS in HR+/HER2- patients of 11.3 weeks.
- The most common of the adverse events (AEs) of any grade occurring in 15 percent or more of patients included nausea (52 percent), fatigue (48 percent), alopecia and peripheral neuropathy (44 percent each) and decreased appetite and vomiting (33 percent each). There was a low incidence of myelosuppression, with grade 3 or 4 adverse events of neutropenia in 19 percent of patients and anemia in 11 percent of patients. Grade 3 peripheral neuropathy occurred in 11 percent of patients.
- The MTD was not reached among doses ranging from 0.5 to 2.8 milligrams per kilogram (mg/kg). Dose escalation is complete.
- Enrollment in a TNBC expansion cohort is ongoing.
More information about the SGN-LIV1A phase 1 clinical trial, including enrolling centers, is available by visiting www.clinicaltrials.gov.
About SGN-LIV1A
SGN-LIV1A is an ADC that combines a humanized anti-LIV-1 monoclonal antibody linked to a synthetic cytotoxic cell-disrupting agent, monomethyl auristatin E (MMAE). The ADC is designed to bind to LIV-1 proteins, which are expressed in most subtypes of metastatic breast cancer, and to release the potent cytotoxic agent MMAE into the target cell upon internalization into LIV-1-expressing tumor cells. This approach is intended to spare non-targeted cells and may reduce many of the toxic effects of traditional chemotherapy while enhancing the antitumor activity.
About Breast Cancer
While there are several therapies available or in development for breast cancer, there remains a significant need to identify improved treatment options. Breast cancer is a disease where malignant (cancer) cells form in the tissue of the breast. Metastatic breast cancer occurs when the cancer has spread to other parts of the body. Breast cancer is the most common cancer, excluding non-melanoma skin cancer, and the second leading cause of cancer death in women. The American Cancer Society estimates that more than 234,000 new cases of breast cancer will be diagnosed in the United States in 2015, and more than 40,000 people will die from the disease. 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.
About Seattle Genetics
Seattle Genetics is a biotechnology company focused on the development and commercialization of innovative antibody-based therapies for the treatment of cancer. Seattle Genetics is leading the field in developing antibody-drug conjugates (ADCs), a technology designed to harness the targeting ability of antibodies to deliver cell-killing agents directly to cancer cells. The company’s lead product, ADCETRIS® (brentuximab vedotin) is a CD30-targeted ADC that, in collaboration with Takeda Pharmaceutical Company Limited, is commercially available in more than 55 countries, including the U.S., Canada, Japan and members of the European Union. Additionally, ADCETRIS is being evaluated broadly in more than 70 ongoing clinical trials in CD30-expressing malignancies. Seattle Genetics is also advancing a robust pipeline of clinical-stage programs, including vadastuximab talirine (SGN-CD33A; 33A), denintuzumab mafodotin (SGN-CD19A; 19A), SGN-LIV1A, SGN-CD70A, ASG-22ME, ASG-15ME and SEA-CD40. Seattle Genetics has collaborations for its ADC technology with a number of leading biotechnology and pharmaceutical companies, including AbbVie, Agensys (an affiliate of Astellas), Bayer, Genentech, GlaxoSmithKline and Pfizer. More information can be found at www.seattlegenetics.com.
SOURCE: Seattle Genetics
