Updated results from a Phase II clinical study of sacituzumab govitecan, also known as IMMU-132, in patients with metastatic triple-negative breast cancer who had received a median of 5 (range, 2 – 12) prior lines of therapy were presented earlier this year during the San Antonio Breast Cancer Symposium (SABCS) being held December 8 – 12, 2015, in San Antonio, Texas.
Sacituzumab govitecan is a first-in-class antbody-drug conjugate or ADC developed by conjugating the moderately-toxic drug, SN-38, site-specifically and at a high ratio of drug to antibody, to a 
humanized antibody that targets the TROP-2 receptor expressed by many solid cancers. SN-38 is the active metabolite of irinotecan (Camptosar; Pfizer), which is used to treat certain solid cancers as a part of combination therapies, so its pharmacology and properties are well- known.
Despite this late-stage setting, sacituzumab govitecan, as a single agent, produced an interim Objective Response Rate (ORR) of 31% by RECIST 1.1 in 58 evaluable patients, with 78% of these responding patients confirmed with a follow-up computed tomography scan, including 2 patients with a complete response. The investigational antibody-drug conjugate is being developed by Immunomedics, a clinical stage biopharmaceutical company.
A serious disease
Triple-negative breast cancer is a serious disease, with an annual incidence estimated to be about 40,000 people, 20,000 for metastatic triple-negative breast cancer, in the United States. Ths from f cancer is insensitive to most of the available targeted therapies for breast cancer treatment, including HER2-directed therapy such as Herceptin® (trastuzumab; Genentech/Roche), and endocrine therapies (such as tamoxifen or the aromatase inhibitors). The median overall survival is 10-13 months and the median PFS is usually 3-4 months. There is currently no single standard chemotherapy to treat patients with relapsed/refractory mTNBC. Rapid relapse, with visceral and brain metastases are very common.
Among the 60 intent-to-treat patients, the interim median Progression-Free Survival (PFS) was 6.0 months, with 58% of these patients having experienced a PFS event. Importantly, to correlation between PFS and (R=0.62, P<0.001) for the 31 patients whose cancer had progressed after reporting stable disease, partial or complete response as their best response. Median overall survival data were too early to report, with 83% of patients still alive.
Acceptable safety profile
Sacituzumab govitecan has an acceptable interim safety profile in the 60 metastatic triple-negative breast cancer patients reported at the symposium. The major toxicity was Grade 3 or 4 neutropenia in 15% of patients. Severe diarrhea, commonly reported with irinotecan, was rare with only 5% Grade 3/4 incidents. Moreover, repeated doses can be given over months without evoking interfering anti- sacituzumab govitecan antibodies from patients’ own immune system.
“This study provides us with a strong basis for a first pivotal Phase III trial in mTNBC, and we will continue the regulatory and manufacturing activities in calendar year 2016,” noted Cynthia L. Sullivan, President and Chief Executive Officer. “We are fully committed to partnering this important Phase III asset, and that partnership will include the full dedication to progress sacituzumab govitecan not only in triple-negative breast cancer, but simultaneously in other indications.”
Regulatory status
Earlier this year, Immunomedics has filed a multicenter, international, randomized, open-label Phase III study of approximately 328 patients with mTNBC who are refractory or relapsing after at least 2 prior chemotherapies that included a taxane for their metastatic disease. In accordance with the Company’s Special Protocol Assessment (SPA) agreement with the U.S. Food and Drug Administration, the primary endpoint of the trial will be PFS, which will be measured by an independent centralized and blinded group of radiology experts who will be assessing tumor response using RECIST 1.1 criteria. Overall survival, Objective Response Rate, duration of response, and time to onset of response will serve as secondary endpoints.
The Phase II study was updated by Aditya Bardia, MD, MPH, Assistant Professor of Medicine at Harvard Medical School, Attending Physician at the Massachusetts General Hospital Cancer Center in Boston, and an investigator in this trial. Steven Jay Isakoff, MD, PhD, as well as Bardia and other colleagues also participated in this multicenter study.
Sacituzumab govitecan has received Fast Track designation from the U.S. Food and Drug Administration (FDA) for the treatment of patients with triple-negative breast cancer, small-cell and non-small-cell lung cancers, and has also been designated an orphan drug for the treatment of patients with small-cell lung or pancreatic cancer in the U.S., and for the treatment of patients with pancreatic cancer in the European Union.
