One in three women with metastatic triple-negative breast cancer — all of whom had received at least two prior treatments — saw their tumors shrink after receiving Immunomedics‘ investigational treatment sacituzumab govitecan as part of a Phase 1/2 trial, a new study shows.
In addition to increasing response rates, the treatment also extended the time patients lived without their disease worsening, compared to previous patients given standard chemotherapy.
Findings from this clinical trial were published in the New England Journal of Medicine, in the study, “Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer.”
“I think this drug has the potential to change practice, because the data look so compelling, even with the relatively small number of patients in the trial,” senior author Kevin Kalinsky, MD, MS, assistant professor of medicine at Columbia University Vagelos College of Physicians and Surgeons, said in a press release.
“There’s an unmet need for patients with metastatic triple-negative breast cancer, and we see significant tumor shrinkage with this new therapy,” said Kalinsky, who is also an oncologist at Columbia University Irving Medical Center and NewYork-Presbyterian.
Triple-negative breast cancer is an aggressive kind of cancer that does not produce any of the three most common breast cancer markers — estrogen receptors, progesterone receptors, and excess HER2 protein. Thus, this cancer does not respond to hormone therapies or HER2-targeted therapies and standard therapeutic options are limited to chemotherapy.
Sacituzumab govitecan is a compound that combines an antibody against the TROP-2 protein — found in many tumor types, including more than 90% of TNBC patients — with a toxic payload. Once bound to its target, sacituzumab govitecan releases the toxic compound into cancer cells, triggering their death.
“With this smart drug, we can deliver a much higher dose of the payload since we’re sending it directly to the cancer cells,” Kalinsky said.
Immunomedics’ candidate was tested in a Phase 1/2 trial, called IMMU-132-01 (NCT01631552), in patients with multiple advanced solid cancers who had failed at least one prior treatment for their metastatic disease.
But after the U.S. Food and Drug Administration granted breakthrough therapy status to sacituzumab govitecan for the treatment of metastatic triple-negative breast cancer patients who had received at least two previous therapies for metastatic disease, the trial was amended to include more of these patients.
The trial included 108 patients, median age 55, with metastatic triple-negative breast cancer who received sacituzumab govitecan as a third-line or higher line of therapy. The median number of prior treatments was three, but some patients had received as many as 10 prior therapies.
All patients received sacituzumab govitecan as an infusion on days 1 and 8 of every three-week cycle until their disease worsened or signs of severe toxicity were reported.
After a median follow-up of 9.7 months, 33.3% of patients had seen a reduction in their cancers, including three patients with a complete tumor clearance. Responses lasted a median of 7.7 months; six patients had responses lasting more than 12 months.
At the time of the analysis, 87% of patients had had disease progression, and 71.3% had died, with a median time to disease worsening or death of 5.5 months and a median survival time of 13 months.
Importantly, efficacy was seen regardless of prior taxane or anthracycline treatment — two kinds of chemotherapy — and the duration of treatment was longer than with the immediate previous therapy — 5.1 months versus 2.5 months — providing “further evidence of clinical activity in patients with difficult-to-treat metastatic triple-negative breast cancer,” researchers stated.
Treatment was also well-tolerated, with no treatment-related deaths and three patients discontinuing due to toxicity. The most common serious adverse events were low levels of blood cells, such as neutrophils, leukocytes, and red blood cells.
“We saw significant tumor shrinkage with the drug, and it took longer for the cancer to progress compared to other drugs commonly used to treat metastatic triple-negative breast cancer,” Kalinsky said.
“Importantly, the drug did not cause neuropathy, the numbness and tingling that can be quite painful and limiting for patients,” he said. “Neuropathy can make it difficult to dress oneself or even walk. It is promising to have an active treatment that does not have neuropathy as a side effect.”
Results from this trial were submitted to the FDA for the accelerated approval of sacituzumab govitecan as third-line treatment for advanced triple-negative breast cancer, but the agency rejected the application, saying that more data is needed regarding chemistry, manufacturing, and control.
Meanwhile, the company is conducting a larger Phase 3 trial — called ASCENT (NCT02574455) — to confirm that sacituzumab govitecan is better at delaying disease worsening or death than standard treatments in this patient population.