The decision to halt the study was based on the unanimous recommendation by an independent data safety monitoring committee during its routine review of the ASCENT study.
The phase III confirmatory ASCENT study will be halted due to compelling evidence of efficacy, according to Immunomedics, the company leading the study.1
The decision was based on the unanimous recommendation by an independent data safety monitoring committee (DSMC) during its routine review of the ASCENT study.
ASCENT is designed to validate the promising safety and efficacy data of sacituzumab govitecan observed in a phase II study of heavily pretreated patients with metastatic triple-negative breast cancer (mTNBC). The primary endpoint for the study is progression-free survival, and secondary endpoints include overall survival and objective response, among others.
“It is my distinct honor to have served as Chairperson of the independent DSMC for this important study,” Julie R. Gralow, MD, Jill Bennett Endowed Professor of Breast Cancer at the University of Washington Medicine, as well as member of the Fred Hutchinson Cancer Research Center, said in a press release. “Triple-negative breast cancer is a disease with extremely limited treatment options beyond classic chemotherapy. The remarkable results we observed across multiple endpoints in the ASCENT study warranted early discontinuation of the trial and are indicative of a potential major advance in the treatment of this devastating disease that affects younger women and African American women at higher rates. I look forward to the release of the full and final analyses of these study data when they are available for public presentation.”
The phase I/II trial of sacituzumab govitecan, published in The New England Journal of Medicine, assessed the treatment in the heavily pretreated population, finding that sacituzumab govitecan achieved durable objective responses.2
In the phase I/II cohort of 108 individuals with triple-negative breast cancer studied, patients had received a median of 3 previous therapies (range, 2-10). Moreover, 4 deaths occurred during treatment and 3 patients (2.8%) discontinued treatment due to adverse events.
Grade 3 or 4 adverse events (observed in ≥10% of the patients) included anemia and neutropenia. Additionally, 10 patients (9.3%) had febrile neutropenia.
The response rate was 33.3% (95% CI, 4.9-10.8), which consisted of 3 complete responses and 33 partial responses, and the median duration of response was 7.7 months (95% CI, 4.9-10.8). As assessed by independent central review, these values were found to be 34.3% and 9.1 months, respectively.
Further, the clinical benefit rate was found to be 45.4%. Median progression-free survival was 5.5. months (95% CI, 4.1-6.3), and overall survival was 13.0 months (95% CI, 11.2-13.7).
A resubmitted biologics license application seeking accelerated approval of sacituzumab govitecan for the treatment of patients with mTNBC who have received at least 2 prior therapies for metastatic disease is currently under review by the FDA, with a prescription drug user fee act (PDUFA) target action date of June 2, 2020.
The FDA already previously granted breakthrough therapy designation for sacituzumab govitecan in this disease setting.
1. Immunomedics Announces ASCENT Study to be Stopped for Compelling Efficacy [news release]. Morris Plains, NJ. Published April 6, 2020. immunomedics.com/our-company/news-and-events/immunomedics-announces-ascent-study-to-be-stopped-for-compelling-efficacy/. Accessed April 7, 2020.
2. Bardia A, Mayer IA, Vahdat LT, et al. Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. N Engl J Med. doi:10.1056/NEJMoa1814213.