A first-in-class antibody-drug conjugate (ADC) called IMMU-132, resulted in clinical activity, and was safe and tolerable among patients with heavily pretreated metastatic triple-negative breast cancer.
A first-in-class antibody-drug conjugate (ADC) called IMMU-132, resulted in clinical activity, and was safe and tolerable among patients with heavily pretreated metastatic triple-negative breast cancer (TNBC).
The results of this ongoing phase II clinical trial were presented (LB-C16) at the International Conference on Molecular Targets and Cancer Therapeutics conference, held November 5-9, 2015, in Boston. The conference was organized by the American Association for Cancer Research (AACR) and the National Cancer Institute.
IMMU-132 (sacituzumab govitecan) is an anti-Trop-2 novel antibody drug conjugate that is also being tested in other tumor types, including lung cancer. The anti-Trop-2 antibody is conjugated to SN-38, the active metabolite of CPT-11.
“Trop-2 is a protein present in limited amounts in normal human tissues but widely found in many human cancers. It is expressed in more than 80 percent of TNBC, making it an attractive therapeutic target,” said study author Aditya Bardia, MD, MPH, an assistant professor of medicine at Harvard Medical School, and attending physician of medical oncology at the Massachusetts General Hospital Cancer Center in Boston, in an AACR press release. This antigen is present on several different types of tumors of epithelial origin.
Of the 34 archival tumor samples that could be stained for Trop-2 expression using immunohistochemistry, 97% were positive for the antigen and 79% had a high intensity of staining.
Immunohistochemistry in archival specimens currently shows 97% positivity of Trop-2 among 34 specimens evaluated, with 79% having high intensity (2+/3+) staining.
Of 56 patients with TNBC who had a median six prior lines of therapy, 30% had an overall response including two complete responses. Thus far, there were 15 partial responses. The clinical benefit ratio was 46%. The current progression-free survival (PFS) is 7 months among 40 patients treated at the 10 mg/kg dose. Overall survival data is not yet mature. Twenty-two patients continue to receive treatment and 87% of patients remain alive.
Grade 3 or 4 toxicities experienced by patients included neutropenia (26%), febrile neutropenia (2%), diarrhea (2%), anemia (4%), and fatigue (4%). No patient developed antibodies to SN-38 or the antibody, and no patient discontinued therapy as a result of toxicity from treatment.
“One of the most interesting findings is that the agent was well tolerated by patients, and toxicity was much lower than one would anticipate with chemotherapy agents such as irinotecan,” Bardia noted.
Typically, heavily pretreated metastatic TNBC patients have a median PFS of 3 or 4 months, and patients with TNBC generally have few options for treatment besides chemotoxic therapies.
The study was funded by Immunomedics Inc., which is developing IMMU-132.