Date: 2015-12-13
Type of information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the 38th San Antonio Breast Cancer Symposium (SABCS)
Company: Seattle Genetics (USA - WA)
Product: SGN-LIV1A
Action
mechanism: antibody drug conjugate/ADC. 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.
Disease: LIV-1-expressing metastatic breast cancer
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: This study is being conducted to examine the safety and tolerability of SGN-LIV1A in patients with metastatic breast cancer, and to find the highest dose of the drug that can be given without unacceptable side effects. Other goals of the trial are to find out if SGN-LIV1A has any antitumor effects, to learn about the pharmacokinetics of SGN-LIV1A, and to explore the relationship between antigen expression and SGN-LIV1A effects. (NCT01969643)
Latest
news: * On December 10, 2015, Seattle Genetics 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 (Interim Analysis of a Phase 1 Study of the Antibody-Drug Conjugate SGN-LIV1A in Patients with Metastatic Breast Cancer - Abstract #638). “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,” said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. 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.
