The FDA has granted an accelerated approval to the antibody-drug conjugate sacituzumab govitecan-hziy (Trodelvy) for the treatment of adult patients with metastatic triple-negative breast cancer.
The FDA has granted an accelerated approval to the antibody-drug conjugate (ADC) sacituzumab govitecan-hziy (Trodelvy) for the treatment of adult patients with metastatic triple-negative breast cancer (TNBC) who have received at least 2 prior therapies for metastatic disease.1
The approval was based on findings from a phase 1/2 study of sacituzumab govitecan in TNBC, in which, 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).2 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 approval of Trodelvy, 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,” Aditya Bardia, MD, the lead investigator of the phase 2 study, and director of Precision Medicine at the Center for Breast Cancer, Massachusetts General Hospital Cancer Center and Assistant Professor of Medicine at Harvard Medical School, stated in a press release. “In our trial, Trodelvy demonstrated clinically meaningful responses in patients with difficult-to-treat metastatic TNBC and moves the needle towards better outcomes for patients with metastatic breast cancer.”
Sacituzumab govitecan 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.
The phase 1/2 trial 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%).
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 accelerated approval of sacituzumab govitecan in this setting is contingent on the results of a confirmatory trial. In that regard, Immunomedics, the developer of sacituzumab govitecan, recently announced that the confirmatory phase III ASCENT study exploring sacituzumab govitecan in patients with metastatic TNBC was stopped due to “compelling evidence of efficacy.”3 The company halted the trial based on a unanimous recommendation from the independent Data Safety Monitoring Committee.
“We are proud to bring Trodelvy to patients with metastatic TNBC who are in dire need of new options. Trodelvy has the potential to become a standard of care in in the management of TNBC, and we anxiously await the results of ongoing studies in other types of metastatic breast cancer,” Loretta M. Itri, MD, chief medical officer of Immunomedics, stated. “This approval highlights the potential of our unique ADC platform and strengthens the premise that the Trop-2 antigen found in many solid cancers is an important target for drug delivery. We are committed to broadening the potential use of Trodelvy in other Trop-2-expressing cancers, especially those with unmet need.”