Trodelvy (sacituzumab govitecan), compared with standard chemotherapy, significantly prolonged overall survival and improved the overall response rate of patients with metastatic triple-negative breast cancer (mTNBC) who had at least two prior lines of therapy, a Phase 3 trial reported.
Based on these findings, recently presented as a late-breaking abstract at the European Society for Medical Oncology (ESMO) Virtual Congress 2020, the therapy’s developer, Immunomedics, intends to file a request for Trodelvy’s full approval for this patient group by year’s end.
“We believe these remarkable results should facilitate the establishment of Trodelvy as a new standard of care in patients with third-line mTNBC,” Loretta M. Itri, the company’s chief medical officer, said in a press release.
Immunomedics will submit a supplemental application to the U.S. Food and Drug Administration (FDA) with these confirmatory trial data to support Trodelvy’s full approval, Itri said. The company is also planning to file a request with the European Medicines Agency early next year to possibly “make this important new treatment available to mTNBC patients in Europe.”
Trodelvy is an antibody-drug conjugate, made up of an antibody targeting TROP-2 — a protein found in different types of solid tumors, including more than 90% of those in TNBC patients — that is linked to the toxic compound SN-38. Once the antibody binds to cancer cells that contain the TROP-2 protein on their surface, SN-38 is released, destroying the cells.
The FDA approved Trodelvy in April — under its accelerated approval program — as a third-line treatment for patients with mTNBC based on data from the Phase 1/2 IMMU-132 trial (NCT01631552). Study findings showed Trodelvy was able to reduce tumor size in around a third of the participants, triggering responses lasting a median of 7.7 months.
Trodelvy’s full approval was pending confirmation of these findings in a larger, Phase 3 confirmatory trial, called ASCENT (NCT02574455).
ASCENT enrolled 529 patients with mTNBC who had received at least two prior chemotherapies for metastatic disease. Following enrollment, participants were randomly assigned to Trodelvy or standard chemo (capecitabine, eribulin, vinorelbine, or gemcitabine) until disease progression or unacceptable toxicity.
Its main goal was to demonstrate that Trodelvy was superior to standard chemotherapy at prolonging the time patients lived without disease worsening (progression free survival). Secondary goals included assessments of Trodelvy on patients’ overall survival, response rates, and safety assessments.
Top-line data from ASCENT, announced in July, showed the trial met its primary goal with Trodelvy prolonging the time patients lived without signs of disease progression from a median of 1.7 to 5.6 months.
New data presented at ESMO 2020 showed that compared to chemo, Trodelvy prolonged the time patients lived from a median of 6.7 to 12.1 months.
The proportion of ASCENT patients who responded to treatment was also higher among those who given Trodelvy, 35%, compared with chemo, 5%. The percentage of patients achieving a complete response (complete cancer eradication) was also higher in the Trodelvy group, 4%, than in the chemo group, 1%.
Trodelvy was well-tolerated by patients in ASCENT, with a safety profile that was consistent with its label. No new safety signals nor deaths were observed during the trial. The most common serious or life-threatening adverse events among those given Trodelvy, compared to chemo alone, included neutropenia (51% vs. 33%), diarrhea (10.5% vs. less than 1%), anemia (8% vs. 5%), and febrile neutropenia (6% vs. 2%).
The percentage of adverse events leading to treatment discontinuation were low, and similar among Trodelvy (4.7%) and chemo (5.4%) group patients. As of the March 11 cut-off date for this analysis, 15 patients were still being treated with Trodelvy, while none remained in the chemo treatment control group.
“The randomized Phase 3 study results confirm that sacituzumab govitecan should be considered as a new standard of care in patients with third-line mTNBC,” said Aditya Bardia, MD, MPH, director of Precision Medicine at the Center for Breast Cancer, Mass General Cancer Center and an assistant professor of Medicine at Harvard Medical School. He presented ASCENT findings at the ESMO Congress.
“Ongoing studies are evaluating sacituzumab govitecan in earlier lines of therapy, including the neoadjuvant and adjuvant settings, in combination with other targeted agents, and in patients with hormone receptor-positive, human epidermal growth factor 2-negative metastatic breast cancer, which will help accelerate our efforts to further improve outcomes for patients with breast cancer,” Bardia added.