FDA Assigns Sacituzumab Govitecan Breakthrough Designation for TNBC

The FDA has granted sacituzumab govitecan (IMMU-132) breakthrough therapy designation for the treatment of patients with triple-negative breast cancer (TNBC) following at least 2 treatments for metastatic disease, according to Immunomedics, the manufacturer of the investigational antibody-drug conjugate.

The designation, which will expedite the development and review of sacituzumab govitecan in TNBC, is based on a phase II trial in which the therapy induced a response rate of 31% in heavily pretreated patients with metastatic 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.

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% of TNBC.

Phase II 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 (range, 1-37). Response was measured by RECIST1.1 criteria.

At the data cutoff, 60 patients who had progressed on at least 2 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% having an ECOG performance of 0. The median age was 54 years (range, 31-80 years).

The median number of prior therapies was 5 (range, 2-12). Prior therapies received included cyclophosphamide (93%), doxorubicin (83%), carboplatin (57%), gemcitabine (50%), capecitabine (43%), eribulin (38%), cisplatin (25%), vinorelbine (17%), and bevacizumab (13%).

Eighteen of 58 evaluable patients had a response, for an overall response rate (ORR) of 31%. There were 2 complete responses and 16 partial responses. The clinical benefit ratio (CR + PR + SD) was 53% at ≥4 months and 45% at ≥6 months.

The median progression-free survival (PFS) was 6.0 months (95% CI, 4.1-9.4 months) and the overall survival (OS) data were not yet mature, with 83% 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%), nausea (27%), neutropenia (23%), vomiting (22%), alopecia (18%), anemia (17%), fatigue (17%), constipation (13%), rash (13%), and abdominal pain (10%).

The most frequently reported grade ≥AEs in the 10 mg/kg cohort were neutropenia (15%), leukopenia (8%), diarrhea (5%), fatigue (3%), dyspnea (3%), febrile neutropenia (2%), and anemia (2%).

The planned phase III 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 ≥2 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.


  1. 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.