The designation, which will expedite the development and review of sacituzumab govitecan in TNBC, is based on a phase 2 trial in which the therapy induced a response rate of 31 percent in heavily pretreated patients with metastatic TNBC.
Sacituzumab govitecan (IMMU-132) has received an FDA breakthrough therapy designation for the treatment of patients with triple-negative breast cancer (TNBC) following at least two treatments for metastatic disease. Immunomedics, the manufacturer of the investigational antibody-drug conjugate, made the announcement last week.
The designation, which will expedite the development and review of sacituzumab govitecan in TNBC, is based on a phase 2 trial in which the therapy induced a response rate of 31 percent in heavily pretreated patients with metastatic TNBC. Sacituzumab govitecan is a humanized IgG antibody targeted against Trop-2 conjugated to SN-38, which is an active metabolite of the chemotherapy irinotecan. Trop-2 is expressed in more than 90 percent of TNBC.
“We believe breakthrough therapy designation for IMMU-132 further validates this potential therapeutic for patients with TNBC, and we are delighted to receive this important recognition,” Cynthia L. Sullivan, president and chief executive officer, of Immunomedics, said in a statement. “We continue to assess partnering opportunities while completing the scale-up manufacturing and regulatory activities for an international, randomized, controlled, registration trial in TNBC, based on the special protocol assessment agreement that was already granted by the FDA,” she added.
Phase 2 results for the drug with a data cutoff of November 10, 2015, were presented at the 2015 San Antonio Breast Cancer Symposium. In the study, patients with metastatic TNBC received either 8 or 10 mg/kg of sacituzumab govitecan intravenously on days 1 and 8 of 21-day repeated cycles. Patients received a median number of 8 doses (ranging from one to 37). Response was measured by RECIST1.1 criteria.
At the data cutoff, 60 patients who had progressed on at least two prior treatments, including a taxane, had received sacituzumab govitecan. Seventy percent of these patients had an ECOG performance status of 1, with the remaining 30 percent having an ECOG performance of 0. The median age was 54 years (ranging from 31 to 80 years).
The median number of prior therapies was five (ranging from at least two to 12). Prior therapies received included cyclophosphamide (93 percent), doxorubicin (83 percent), carboplatin (57 percent), gemcitabine (50 percent), capecitabine (43 percent), Halaven (eribulin; 38 percent), cisplatin (25 percent), vinorelbine (17 percent), and Avastin (bevacizumab; 13 percent).
Eighteen of 58 evaluable patients had a response, for an overall response rate (ORR) of 31 percent. There were two complete responses (CR) and 16 partial responses (PR). The clinical benefit ratio (CR + PR + stable disease) was 53 percent after at least four months and 45 percent after at least six months. The median progression-free survival (PFS) was 6.0 months and the overall survival (OS) data were not yet mature, with 83 percent of patients still alive. The 10 mg/kg regimen was the dose selected for future clinical development.
The most common all-grade adverse events (AEs) in the 10 mg/kg arm were diarrhea (27 percent), nausea (27 percent), neutropenia (23 percent), vomiting (22 percent), alopecia (18 percent), anemia (17 percent), fatigue (17 percent), constipation (13 percent), rash (13 percent) and abdominal pain (10 percent).
The most frequently reported AEs of at least grade 3 in the 10 mg/kg cohort were neutropenia (15 percent), leukopenia (8 percent), diarrhea (5 percent), fatigue (3 percent), dyspnea (3 percent), febrile neutropenia (2 percent) and anemia (2 percent).
The planned phase 3 trial of sacituzumab govitecan, on which Immunomedics is working with the FDA, is a multicenter, international, randomized, open-label study that aims to accrue 328 patients with relapsed/refractory metastatic TNBC following at least two prior chemotherapies, including a taxane. The primary outcome measure will be PFS, with secondary endpoints including OS, ORR, duration of response, and time to onset of response.
Bardia A, Diamond R, Mayer A, et al. Safety and efficacy of anti-Trop-2 antibody drug conjugate, sacituzumab govitecan (IMMU-132), in heavily pretreated patients with TNBC. Presented at: the 2015 San Antonio Breast Cancer Symposium; San Antonio, TX; December 8-12, 2015. PD3-06.