FDA Accepts Sacituzumab Govitecan Application for TNBC

The FDA has accepted a biologics license application for sacituzumab govitecan as a treatment for patients with metastatic triple-negative breast cancer who have received at least 2 prior therapies for metastatic disease.

Behzad Aghazadeh

The FDA has accepted a biologics license application (BLA) for sacituzumab govitecan as a treatment for patients with metastatic triple-negative breast cancer (TNBC) who have received at least 2 prior therapies for metastatic disease, according to a statement from the company developing the antibody-drug conjugate (ADC), Immunomedics.1

A prior application for sacituzumab govitecan received a complete response letter (CRL) from the FDA in January 2019, citing chemistry, manufacturing, and control matters, which did not warrant the conduct of a second clinical trial.2 The FDA has assigned June 2, 2020, as the new Prescription Drug User Fee Act (PDUFA) action date for sacituzumab govitecan, which consists of the active metabolite of irinotecan, SN-38, linked with a humanized IgG antibody targeted against TROP-2, a cell-surface glycoprotein that is expressed in more than 90% of TNBC.

“We are pleased that the FDA has accepted our resubmission, which was a top priority for us in 2019,” Behzad Aghazadeh, executive chairman of Immunomedics, the developer of the ADC, stated in a press release. “We look forward to working closely with the FDA to facilitate their review of our BLA to enable us to bring this potentially transformational treatment to patients affected by mTNBC.”

The BLA for sacituzumab govitecan was based on findings from a phase I/II study, which included 108 patients with TNBC at a median age of 55 years (range, 31-80). The majority of patients had visceral metastases (80%). Sacituzumab govitecan was administered at 10 mg/kg on days 1 and 8 of each 28-day cycle. Patients’ ECOG performance status was 0 (30%) and 1 (70%), and the median time from metastatic diagnosis to treatment in the study was 1.5 years. Overall, 57 patients had moderate (2+) to strong (3+) TROP-2 expression by immunohistochemistry and 5 had weak or absent staining for the marker. The data were not available for the remaining patients.

The median number of prior regimens was 3 (range, 2-10), which include checkpoint inhibitors for 16.7%. Additionally, 41% of patients were treated in the third-line setting and 59% were in the fourth-line or greater setting. The most common prior therapies were taxanes (98%), anthracyclines (86%), cyclophosphamide (85%), and platinum agents (75%).

In results, which were published in the New England Journal of Medicine,3 at a median follow-up of 9.7 months the objective response rate (ORR) was 33.3% by local assessment (95% CI, 24.6%-43.1%) with a median duration of response (DOR) of 7.7 months (95% CI, 4.9-10.8). The clinical benefit rate (ORR plus stable disease) was 45.4%. By blinded independent central review, the ORR was 34.3% (95% CI, 25.4%-44.0%) and the median DOR was 9.1 months (95 CI, 4.6-11.3).

The median progression-free survival (PFS) was 5.5 months (95% CI, 4.1-6.3). The estimated 6-month PFS rate 41.9%. By 12 months, the PFS rate with sacituzumab govitecan was estimated at 15.1%. The median overall survival (OS) was 13.0 months (95% CI, 11.2-13.7), with an estimated 6-month OS rate of 78.5% and a 12-month estimate of 51.3%.

Grade 3/4 adverse events (AEs) were experienced by 85% of patients receiving treatment with sacituzumab govitecan. Serious AEs were reported in 35% of patients. Overall, just 3 patients discontinued treatment due to AEs, of these 2 were deemed from study drug-related causes. Dose reductions to 7.5 mg/kg occurred in 25% of patients and the rest were able to continue sacituzumab govitecan at the 10 mg/kg dose.

The most common (≥10%) grade 3/4 AEs were neutropenia (41.7%), anemia (11%), decreased white-cell count (11%), hypophosphatemia (9%), diarrhea (8%), and fatigue and asthenia (8%). Ten patients (9.3%) developed febrile neutropenia during the course of the study. Additionally, 4 deaths occurred during treatment, and 3 patients discontinued due to AEs.

The phase III ASCENT trial is currently exploring sacituzumab govitecan in comparison with treatment of physician choice for patients with metastatic TNBC. The trial, which has fully accrued 529 patients, is expected to report results in 2020 (NCT02574455). The current BLA for sacituzumab govitecan, if approved, will provide an accelerated approval for the medication. Finding from the ASCENT trial will act as confirmation.


  1. Immunomedics Announces FDA Acceptance for Filing of Biologics License Application Resubmission for Sacituzumab Govitecan to Treat Metastatic Triple-Negative Breast Cancer. Immunomedics, Inc. Published December 26, 2019. https://bit.ly/37iQ4ZD. Accessed December 27, 2019.
  2. Immunomedics Receives Complete Response Letter From FDA for Sacituzumab Govitecan Biologics License Application. Immunomedics. Published January 17, 2019. https://bit.ly/2sBcDGG?rel=0" . Accessed January 17, 2019.
  3. Bardia A, Mayer IA, Vahdat LT, et al. Sacituzumab govitecan-hziy in refractory metastatic triple-negative breast cancer. N Eng J Med. 2019;380:741-751. doi: 10.1056/NEJMoa1814213.