Novel breast cancer treatment ready for phase 3 trial
A study of a novel antibody-drug conjugate, led by Priya U. Kumthekar, MD, showed promising results.
The agent appeared to prolong survival for women with breast cancer who had leptomeningeal carcinomatosis and recurrent brain metastases.
“This was a phase 2 study in a difficult-to-treat patient population where the mean survival is usually quite poor,” Kumthekar, assistant professor of neurology at the Northwestern University’s Feinberg School of Medicine, told Healio. “We showed in our study a significant increase in survival following response to this exciting new agent.
“When you have cancer in the cerebrospinal fluid (CSF), which is the fluid surrounding the brain and spinal cord, it’s very difficult to treat,” she continued. “We unfortunately do not have effective options to treat these patients, and leptomeningeal disease is almost uniformly their cause of death. We wanted to go after this population because they are often excluded from trials due to the difficulty of treatment.”
The new compound, ANG1005 (Angiochem), is a novel taxane derivative that consists of three molecules of paclitaxel covalently linked to angiopep-2. Through angiopep-2, the drug is able to cross the blood-brain and blood-cerebrospinal barriers and penetrate malignant cells via the LRP1 transport system.
“Paclitaxel is a tried-and-true cancer treatment, but the method of delivery is what’s different here,” Kumthekar said. “We’re using a drug that we have reason to believe will work, but now we’re actually getting the drug to the right place.”
The study included 72 women (median age, 47.5 years) with breast cancer-related brain metastases, 28 of whom were diagnosed with leptomeningeal carcinomatosis, including 16 with HER2-positive and 12 with HER2-negative disease.
The researchers observed stable disease or better in 77% (intracranial) and 86% (extracranial) of evaluable women and reported intracranial objective response rates of 15% according to investigator assessment and 8% based on independent radiology facility review.
Among women with leptomeningeal carcinomatosis, 79% had intracranial disease control and estimated median OS of 8 months (95% CI, 5.4–9.4).
The OS rate at 6 months was 56% (95% CI, 43-66) among all patients, 67% (95% CI, 47-81) among HER2-positive patients and 47% (95% CI, 30-62) among HER2-negative patients. Additionally, Kaplan-Meier-estimated median OS was 7.8 months (95% CI, 5.1-9) for all, 9.9 months (95% CI, 5.6-12) for HER2-positive patients and 4.3 months (95% CI, 3.4-8) for HER2-negative patients.
Safety and tolerability of the treatment appeared consistent with historic taxane profile.
“We plan to open the multisite registrational phase 3 study in approximately the first quarter of 2021 and we are very excited for the potential to be able to offer this treatment to patients one day,” Kumthekar noted.
Kumthekar will chair the randomized open-label phase 3 study, for which the researchers have a special protocol agreement with the FDA. The study design includes 150 patients across 30 U.S. study centers. Kumthekar and colleagues will evaluate treatment outcomes of ANG1005 compared with “physician’s best choice” among patients with breast cancer with newly diagnosed leptomeningeal carcinomatosis.
“If that study is positive, we will have a new treatment option for these patients who really need it,” she said.
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Priya U. Kumthekar, MD, is a member of the Peer Perspective Board for Healio’s Women in Oncology. She can be reached at: Priya.Kumthekar@nm.org.