The FDA has granted a priority review designation to a biologics license application (BLA) for sacituzumab govitecan for the treatment of patients with metastatic triple-negative breast cancer (mTNBC) following at least 2 prior therapies for metastatic disease, according to Immunomedics, the manufacturer of the antibody-drug conjugate.
In phase II results presented at the 2017 San Antonio Breast Cancer Symposium (SABCS), sacituzumab govitecan elicited an objective response rate (ORR) of 34% in patients with heavily pretreated mTNBC. In the 110-patient, single-arm trial, the ORR was accompanied by stable disease for ≥6 months in 11% of patients, for an overall disease control rate of 45%. The median progression-free survival with sacituzumab govitecan was 5.5 months (95% CI, 4.8-6.6) and the median overall survival was 12.7 months (95% CI, 10.8-13.6).
Under the Prescription Drug User Fee Act, the FDA is scheduled to make its decision on the BLA by January 18, 2019.
“We are delighted that the FDA has accepted the sacituzumab govitecan BLA for priority review,” Michael Pehl, president and chief executive officer, Immunomedics, said in a statement. “We will continue to work closely with the regulatory agency as we strive to bring this potential new treatment to mTNBC patients expeditiously.”
Sacituzumab govitecan is an antibody-drug conjugate that 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. In the study presented at SABCS, 57 patients had moderate (2+) to strong (3+) TROP-2 expression by IHC and 5 had weak or absent staining for the marker. Data were not available for the remaining patients.
The study included 110 patients at a median age of 55 years (range, 31-81). Sacituzumab govitecan was administered at 10 mg/kg on days 1 and 8 of each 28-day cycle, which is the same dose being used in the phase III study. Patients had received a median of 14.5 doses of the medication (range, 1-88) and the median duration of treatment was 4.9 months (range, 0.2-32.1).
The 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. Forty-one percent of patients were treated in the third-line setting and 59% were in the fourth line or greater. The most common prior therapies were taxanes (98%), anthracyclines (86%), cyclophosphamide (85%), and platinum agents (75%). Additionally, 17% of patients had received an immune checkpoint inhibitor. Most patients had visceral metastases (80%).
By blinded independent central review, the ORR was 31%, which confirmed findings seen in the local assessment, Bardia said. By local assessment there were 3 complete responses (CRs) and 34 partial responses (PR). There were 6 CRs and 28 PRs in the blinded review. A target lesion reduction was seen in approximately 74% of patients, suggesting that most patients experienced some type of response to the medication, Bardia said.
The median duration of response by local review was 7.6 months and was 9.1 months in the blinded assessment. The median time to onset of response was 2.0 months (range, 1.5-13.4). There were 9 long-term responders who remained progression-free for >1 year from the start of treatment, with 4 of these individuals experiencing a response for greater than 2 years. Twelve patients continued treatment at the data cutoff in June 2017.
In an exploratory analysis, responses looked similar across subgroups. TROP-2 expression did not appear to impact activity; however, there were limited data for this assessment. Those receiving prior checkpoint inhibitors had an ORR of 47% (9 of 19) and responses were similar between those receiving treatment as a third-line therapy or beyond (36% and 32%, respectively). In those with and without visceral metastases, the ORRs were 30% and 50%, respectively.
The most common all grade adverse events (AEs) were neutropenia (63%), nausea (63%), diarrhea (56%), anemia (52%), fatigue (50%), and vomiting (46%). The most common AEs of grade 3 or 4 in severity were neutropenia (41%), leukopenia (14%), anemia (10%), diarrhea (8%), hypophosphatemia (8%), and fatigue (7%). Febrile neutropenia occurred in 8% of patients, and was primarily grade 3/4 in severity (7% of patients). The rate of neutropenia seen in the study was contributed to the release of SN-38 in the tumor microenvironment, as this AE is also common with irinotecan.
Twenty-five percent of patients had a dose reduction to 7.5 mg/kg and the rest were able to continue sacituzumab govitecan at the 10 mg/kg dose. Two patients discontinued due to AEs and there were no treatment-related deaths in this study.
In February 2016 the FDA granted a breakthrough therapy designation to sacituzumab govitecan as a treatment for TNBC following at least 2 treatments for metastatic disease.
Bardia A, Vahdat LT, Diamond J, et al. Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate, as ≥3rd-line therapeutic option for patients with relapsed/refractory metastatic triple-negative breast cancer (mTNBC): efficacy results. Presented at: 2017 San Antonio Breast Cancer Symposium; San Antonio, Texas, December 5-9, 2017. Presentation GS1-07.