FDA Grants Accelerated Approval to Sacituzumab Govitecan in mTNBC


"The approval of sacituzumab govitecan, the first ADC approved specifically for metastatic TNBC, an aggressive cancer with a poor prognosis and few effective therapies, will give clinicians a novel tool for treating patients with this disease."

The FDA has accelerated approval to sacituzumab govitecan-hziy (Trodelvy) for the treatment of adult patients with metastatic triple-negative breast cancer (mTNBC) who have received at least 2 prior therapies for metastatic disease.1

“The approval of Trodelvy, the first ADC approved specifically for mTNBC, an aggressive cancer with a poor prognosis and few effective therapies, will give clinicians a novel tool for treating patients with this disease,” stated Aditya Bardia, MD, MPH, director of precision medicine at the Center for Breast Cancer, Massachusetts General Hospital Cancer Center and assistant professor of medicine at Harvard Medical School, and lead investigator for the study of this agent. “In our trial, Trodelvy demonstrated clinically meaningful responses in patients with difficult-to-treat mTNBC and moves the needle towards better outcomes for patients with metastatic breast cancer.”

Sacituzumab govitecan was granted Breakthrough Therapy Designation for this indication based on positive efficacy results from mTNBC cohort of the phase III ASCENT study, which were published in the New England Journal of Medicine.

The efficacy analysis included 108 patients total, who achieved a response rate was 33.3% (95% CI, 24.6%-43.1%), which included complete responses in 2.8% of patients, per local assessment. Partial responses were observed in 30.6% of patients, per investigator assessment. Also, 37.0% of patients had stable disease and 25.9% of patients had progressive disease. The clinical benefit rate was 45.4%, which included stable disease for at least 6 months.2

In the treatment responders (n = 39), the median time to response was 2.0 months (range, 1.6-13.5) and there was a 7.7-month median duration of response ([DOR]; 95% CI, 4.9-10.8). Data were also evaluated by blinded independent review, which showed a similar response rate of 34.3% (95% CI, 25.4%-44.0%) and median DOR of 9.1 months (95% CI, 4.6-11.3). According to local assessment, sacituzumab govitecan had a 59.7% estimated probability of eliciting response at 6 months. The estimated probability that patients would respond to treatment at 12 months was 27.0%. Long-term responses of over 12 months (range 12.7-30.4) were observed in 6 of the responders at the time of data cutoff.

The subgroup of patients in the study included those from various ages groups, metastatic disease status, number of previous therapies, and the presence or absence of visceral metastases. Among these groups, there were no differences in response.

Eight-seven percent of patients had disease progression (n = 94), and 71.3% of patients died (n = 77), as of data cutoff. In terms of progression-free survival (PFS), the median PFS was 5.5 months (95% CI, 4.1-6.3), and the estimated probability of PFS was 41.9% at 6 months and 15.1% at 12 months. Median overall survival (OS) was 13.0 months (95% CI, 11.2-13.7), with an estimated probability of survival of 78.5% at 6 months and 51.3% at 12 months.

The durability of previous therapy was compared to the durability of treatment with sacituzumab govitecan in the study, as a means to determine if response were \affected by how aggressive the treatment was. This analysis showed that DOR with sacituzumab govitecan (5.1 months) was twice as long as prior therapy (2.5 months).

The safety analysis of sacituzumab govitecan showed tolerability with the agent. The most common any-grade adverse events (AEs) were nausea (67%), neutropenia (64%), diarrhea (62%), fatigue (55%), and anemia (50%). In terms of grade 3 or higher AEs, the most common (>5%) being neutropenia (n = 45), anemia (n = 12), and a decreased white cell count (n = 2).

Overall, 44% of patients in the study had treatment interruptions as a result of AEs. Treatment discontinuation occurred in 3% of patients and there were 4 deaths.

In the ongoing ASCENT trial, patients were randomized 1:1 to receive either sacituzumab govitecan or treatment of physician’s choice. Sacituzumab govitecan was administered at a dose of 10 mg/kg. In addition to relapsed or refractory TNBC, the cohort being studied in ASCENT include gastric adenocarcinoma, esophageal cancer, hepatocellular carcinoma, non-small cell lung cancer, small cell lung cancer, ovarian epithelial cancer, carcinoma breast stage IV, hormone-refractory prostate cancer, head and neck cancers- squamous cell, renal cell cancer, urinary bladder neoplasms, cervical cancer, endometrial cancer, follicular thyroid cancer, glioblastoma multiforme, and pancreatic cancer.

The primary end point is ORR. The secondary end points include DOR, clinical benefit rate, PFS, and OS.

The original Biologic License Application for sacituzumab govitecan for this indication was denied by the FDA due to lack of necessary data, according to a Complete Response Letter issued in January of 2019. The ASCENT data fulfilled this lack of information.3

“We are proud to bring Trodelvy to patients with mTNBC who are in dire need of new options. Trodelvy has the potential to become a standard of care in the management of TNBC, and we anxiously await the results of ongoing studies in other types of metastatic breast cancer,” said Loretta M. Itri, MD, chief medical officer of Immunomedics, in a statement.1


1. FDA grants accelerated approval for immunomedics’ trodelvy in previously-treated metastatic triple negative breast cancer [news release]. Morris Plains, NJ: Immunomedics, Inc: April 22, 2020. https://bit.ly/3cJ0EM. Accessed April 22, 2020

2. Bardia A, Mayer IA, Vahdat LT, et al. Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer.N Engl J Med. 2019;380 (8):741-51. doi: 10.1056/NEJMoa1814213

3. Immunomedics receives complete response letter from fda for sacituzumab govitecan biologics license application [news release]. Morris Plains, NJ: Immunomedics, Inc; January 17, 2019. https://bit.ly/3bqyjtI. Accessed April 22, 2020.

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