Immunomedics has resubmitted its biologics license application to the FDA for sacituzumab govitecan for the treatment of patients with metastatic triple-negative breast cancer who have received ≥2 prior therapies for metastatic disease.
Immunomedics has resubmitted its biologics license application (BLA) to the FDA for sacituzumab govitecan for the treatment of patients with metastatic triple-negative breast cancer (TNBC) who have received ≥2 prior therapies for metastatic disease.1
“We appreciate the FDA’s guidance during the resubmission period and look forward to working closely with the agency during the BLA review,” Behzad Aghazadeh, executive chairman of Immunomedics, the developer of the antibody-drug conjugate, stated in a press release. “We are pleased to have reached this important milestone and believe that sacituzumab govitecan, if approved, could become an important new treatment option for patients with late-stage mTNBC.”
The resubmission follows a complete response letter (CRL) the FDA submitted to the company in January 2019, citing chemistry, manufacturing, and control matters related to the BLA.2
The FDA previously granted a priority review designation to the BLA for sacituzumab govitecan in July 2018, and was originally scheduled to make its decision on the application by January 18, 2019.
The BLA was based on phase I/II results that were presented at the 2017 San Antonio Breast Cancer Symposium (SABCS), in which sacituzumab govitecan demonstrated an objective response rate (ORR) of 34% in patients with heavily pretreated mTNBC.3
In the 110-patient, single-arm study, 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).
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 that was presented at the 2017 SABCS, 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 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).
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. 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%). Additionally, 17% of patients had received an immune checkpoint inhibitor. The majority of patients had visceral metastases (80%).
The ORR was 31% by blinded independent central review, which confirmed findings seen in the local assessment. There were 3 complete responses (CRs) and 34 partial responses (PR) by local assessment; 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.
Moreover, the median duration of response (DOR) 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.
Updated results of the study were published in the New England Journal of Medicine (NEJM) with a total 108 patients at a median follow-up of 9.7 months.4 Here, the ORR was 33.3% (95% CI, 24.6-43.1) with a median DOR of 7.7 months. Via independent central review, the ORR was 34.3% and the median DOR was 9.1 months. The clinical benefit rate was 45.4%, the median PFS was 5.5 months (95% CI, 4.1-6.3), and the median OS was 13.0 months (95% CI, 11.2-13.7).
Regarding safety, the data published in NEJM is the most common (≥10%) grade 3/4 adverse events (AEs), which included anemia and neutropenia. A total 10 patients (9.3%) had febrile neutropenia. Additionally, 4 deaths occurred during treatment, and 3 patients discontinued due to AEs.
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.