"The results of the global phase 3 ASCENT study confirm our initial observations that sacituzumab govitecan has the potential to change the standard management of mTNBC."
Sacituzumab govitecan-hziy (Trodelvy) monotherapy improved progression-free survival (PFS) compared with chemotherapy in patients with brain metastasis-negative metastatic triple-negative breast cancer (mTNBC) who received at least 2 prior therapies, meeting the primary end point of the phase 3 ASCENT trial (NCT02574455).
“The results of the global phase 3 ASCENT study confirm our initial observations that sacituzumab govitecan has the potential to change the standard management of mTNBC. Based on these data, sacituzumab govitecan has set a new benchmark in scientific and clinical innovation for patients with mTNBC by offering a novel alternative to the common drugs currently in clinical practice. Importantly, the ASCENT topline data also validate the manageable safety profile of sacituzumab govitecan, rendering it a good partner candidate for combination with other therapies, including immunotherapy,” stated the study principal investigator, Aditya Bardia, MD, MPH, director of Precision Medicine at the Center for Breast Cancer, Mass General Cancer Center and assistant professor of Medicine at Harvard Medical School.
The hazard ratio for the difference in PFS between the sacituzumab govitecan and chemotherapy arms was 0.41 (95% CI, 0.32-0.52). With sacituzumab govitecan, the median PFS was 5.6 months (95% CI, 4.3-6.3) versus 1.7 months (95% CI, 1.5-2.6) with chemotherapy (P <.0001). Sacituzumab govitecan also improved overall survival and demonstrated a superior objective response rate (ORR) compared with chemotherapy, which are 2 secondary end points.
In terms of safety, results were consistent with the FDA-approved drug label. The most common grade 3/4 adverse events (AEs) observed were neutropenia and diarrhea. No new safety signals were observed in the study.
Full results from the study will be presented at an upcoming medical meeting.
Prior to these phase 3 results, the antibody-drug conjugate, sacituzumab govitecan was granted accelerated approval by the FDA for the third-line treatment of adult patients with mTNBC based on phase 1/2 ASCENT trial results showing a positive ORR and duration of response (DOR). According to data published in the New England Journal of Medicine from 108 patients, the response rate achieved with sacituzumab govitecan was 33.3% (95% CI, 24.6%-43.1%) with a complete response rate of 2.8% and a partial response rate of 30.6%. In addition, 37.0% of patients achieved stable disease. The median DOR in the 39 responders was 7.7 months (95% CI, 4.9-10.8) per local assessment.
Similar to that reported from the phase 3 study, the most common any-grade AEs nausea (67%), neutropenia (64%), diarrhea (62%), fatigue (55%), and anemia (50%), and the most common grade 3/4 AEs were neutropenia (n = 45), anemia (n = 12), and a decreased white cell count (n = 2).
ASCENT is an international, open-label, confirmatory study that enrolled over 500 patients with mTNBC who received a minimum of 2 prior lines of therapy. Patients in the study are randomized 1:1 to receive sacituzumab govitecan at 10 mg/kg on days 1 and 8 of 21-day cycles. Chemotherapy of the physician’s choice includes either eribulin 1.4 mg/kg, capecitabine 1000-1250 mg/m2, gemcitabine 800-1200 mg/m2, or vinorebine 25mg/m2.
Patients were eligible to enroll in the study given they had a histologically or cytologically confirmed TNBC, relapsed or refractory disease following 2 prior lines of treatment, prior exposure to a taxane agent in the localized or advanced/metastatic settings, an ECOG performance status of 0 or 1, measurable disease per cat scan or MRI, and adequate hematologic lab values.
The ASCENT trial is ongoing with a target completion date of July 2020.
“It is gratifying to see the final confirmatory results of Trodelvy in a randomized study supporting the previously reported phase 2 data that formed the basis of the accelerated approval of Trodelvy. These results provide important additional information for patients and their treating physicians to understand the definitive benefits they are deriving,” commented Dr. Behzad Aghazadeh, executive chairman, Immunomedics. “Importantly, the strong ASCENT data reinforce the promise of our unique antibody-drug conjugate technology and embolden us to continue our work to change the treatment paradigm for patients with difficult-to-treat cancers.”
1. Immunomedics announces positive results from phase 3 ASCENT study of Trodelvy. News release. Immunomedics, Inc. July 6, 2020. https://bit.ly/31RebPG.
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