A Phase 3 clinical trial investigating Immunomedics‘ potential therapy sacituzumab govitecan is ending early because existing results have shown sufficient evidence that the treatment is effective in patients with triple-negative breast cancer (TNBC).
The decision to stop the trial was unanimously recommended by an independent data safety monitoring committee.
An application to obtain approval for sacituzumab govitecan for patients with metastatic TNBC who received at least two prior therapies is being reviewed by the U.S. Food and Drug Administration. A decision is expected by June 2.
“The remarkable results we observed across multiple endpoints [goals] in the ASCENT study warranted early discontinuation of the trial and are indicative of a potential major advance in the treatment of this devastating disease that affects younger women and African American women at higher rates,” Julie R. Gralow, MD, said in a press release. Gralow is chairwoman of the committee and a professor at the University of Washington School of Medicine.
TNBC is so named because patients’ cancer cells do not express elevated levels of three markers: hormone epidermal growth factor receptor 2 (HER-2); estrogen receptors (ER); and progesterone receptors (PR), which are associated with breast cancer growth.
Breast cancer treatments typically target these markers, leaving very limited options for TNBC patients. Classic chemotherapy is used primarily in such cases.
Sacituzumab govitecan is an antibody-drug conjugate (ADC) treatment, as it combines an antibody-driven immunotherapy approach to locate cancer cells with an anti-cancer molecule designed for the target of interest.
Immunomedics’ approach to designing ADCs involves using a molecule known as SN-38, considered less toxic than other alternatives. SN-38 is the active ingredient of the approved chemotherapy irinotecan (marketed as Camptosar, among others).
In sacituzumb govitecan, SN-38 is directly attached to hRS7, an antibody that specifically targets the TROP-2 protein. TROP-2 is found on the surface of cells, and its levels are higher on tumor cells compared to healthy cells.
Upon binding of hRS7 to TROP-2, SN-38 is released to kill the targeted cancer cells.
A Phase 1/2 trial (NCT01631552) previously had shown that treatment with sacituzumab govitecan resulted in tumor shrinkage in one in three women with metastatic TNBC, while also extending survival compared to chemotherapy.
The ASCENT Phase 3 trial (NCT02574455) was designed to confirm these benefits in patients with relapsing or refractory TNBC after at least two previous chemotherapies.
The study recruited 529 patients at 230 sites across the U.S., Canada, and Europe. Its primary goal was measuring progression-free survival (the amount of time during and after treatment without cancer progression).
Secondary assessments included overall survival, the proportion of patients with tumor shrinkage or disappearance (known as objective response rate), how long it takes for the treatment to work, and duration of response.
Treatment with sacituzumab govitecan was compared to a control group in which patients received one of four chemotherapy treatments: Halaven (eribulin); capecitabine (marketed as Xeloda among others); gemcitabine (sold as Gemzar among others); or vinorelbine (Navelbine among others).
“Today’s announcement marks a significant milestone towards fulfilling our promise to patients globally with TNBC of providing a new treatment option that can meaningfully improve their lives,” said Behzad Aghazadeh, PhD, Immunomedics executive chairman.
“We are grateful to all the patients, their families and healthcare providers who participated in the ASCENT study. On behalf of all of my colleagues at Immunomedics, we remain committed to working tirelessly to bring this potentially transformative drug to all [metastatic TNBC] patients in need,” Aghazadeh said.
Loretta M. Itri, MD, chief medical officer of Immunomedics, said: “This strengthens our resolve to complete the analysis and reporting of the final study results, thereby allowing these data to become available to physicians caring for the TNBC community in a timely fashion.”