MORRIS PLAINS, N.J.—Biopharmaceutical company Immunomedics Inc. announced that its Phase 3 confirmatory ASCENT study on sacituzumab govitecan will be halted early due to “compelling evidence of efficacy,” thus fast-tracking the novel antibody-drug conjugate (ADC) designed to battle triple-negative breast cancer (TNBC). This decision was based on the unanimous recommendation by the data safety monitoring committee (DSMC) following a recent review of the ASCENT study.
“If sacituzumab govitecan is approved, clinicians will have a novel tool to treat patients with this aggressive form of breast cancer,” Usama Malik, chief financial officer of Immunomedics, tells DDNews. “This would absolutely be a game-changer for this population. Sacituzumab govitecan would be the first and only ADC FDA-approved specifically for the treatment of patients with mTNBC [metastatic TNBC].”
TNBC is an aggressive disease accounting for approximately 15 percent of all breast cancer types in the United States alone. The incidence rate is higher among women under 40, and highest among African-American and Hispanic women.
Sacituzumab govitecan is currently under FDA review, with a PDUFA date of June 2, 2020. Conditional approval on June 2 was contingent on positive ASCENT study data, and the DSMC’s vote cleared a significant time hurdle for this potential treatment.
“An overall response rate of about 10 percent, and median progression-free survival of two to three months, have recently been reported in late-stage mTNBC using single-agent chemotherapy,” Malik says. “People treated with sacituzumab govitecan had a median of more than five months progression-free survival.”
Since TNBC tumors do not have sufficient estrogen, progesterone or HER2 receptor expression to indicate the use of hormonal or HER2-directed therapy, there is currently no standard-of-care chemotherapy for people with relapsed/refractory mTNBC.
Sacituzumab govitecan works by delivering SN-38, a potent topoisomerase I inhibitor, directly to tumor cells by targeting the Trop-2 antigen expressed by many solid cancers.
“Additionally, there are no current approved chemotherapies for this population, and sacituzumab govitecan has the potential to become the standard of care,” Malik notes. “Previous clinical study data with sacituzumab govitecan demonstrated a clinical benefit rate of 45.4 percent, which means that close to 50 percent of patients in that study had achieved complete response (100-percent tumor shrinkage), partial response (≥30-percent tumor shrinkage) or stable disease for six months or longer.”
“This means that, on average, patients responded favorably to our potential treatment for a significantly longer time, improving their overall quality of life,” he continues, adding that an overall response rate of 33.3 percent was observed in the single-arm Phase 2 study of sacituzumab govitecan, which means a third of the patients in that study had their tumors shrunk by 30 percent or more after receiving treatments with sacituzumab govitecan.
According to Malik, patient responses “were durable, with a median duration of 7.7 months. It is important to note that these were very sick patients. They had received a median of three prior treatments for their disease. In this late-stage setting, only one in 10 patients responded to single-agent chemotherapy, which is very toxic.”
“Triple-negative breast cancer is a disease with extremely limited treatment options beyond classic chemotherapy,” stated Dr. Julie R. Gralow, chairperson of the study’s DSMC. “The remarkable results we observed across multiple endpoints 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.”
Loretta M. Itri, chief medical officer of Immunomedics, remarks, “We want to thank the members of the DSMC for their guidance. 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.”
Dr. Behzad Aghazadeh, executive chairman of Immunomedics, adds that the DSMC decision to stop the study “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 ... We remain committed to working tirelessly to bring this potentially transformative drug to all mTNBC patients in need.”
A biologics license application resubmission is currently under FDA review in hopes of accelerated approval of sacituzumab govitecan for the treatment of patients with mTNBC who have received at least two prior therapies for metastatic disease. The FDA previously granted Breakthrough Therapy Designation for sacituzumab govitecan with a top-line readout expected around mid-2020.
Immunomedics’ ASCENT study was designed to validate safety and efficacy data observed in a Phase 2 study of heavily pretreated patients with mTNBC. The primary endpoint for the study is progression free survival, and secondary endpoints include overall survival and an objective response rate, among others.