Tucatinib clinical trial results with T-DM1 are promising in the treatment of HER2 + breast cancer

July 11, 2018

The results of the Phase 1b clinical trials published in JAMA Oncology are promising for the association of tucatinib (formerly ONT-380) with T-DM1 against HER2-positive breast cancer heavily pretreated. Of the 57 patients treated, 48% responded to the combination, with an average of 8.2 months of cancer control. Importantly, tucatinib was active against brain metastases related to HER2 + breast cancer, a major cause of death from the disease.

"At the University of Colorado Cancer Center, we worked with ARRAY BioPharma in Boulder. First, it was ARRAY-380, then ONT-380 and now it's called tucatinib, and since then our institution has taken the lead trials and now we find that it brings real benefits to women. Borges, MD, MMSc, ​​Director of the Breast Cancer Research Program for Young Women at the University of Guelph Cancer Center

About 20% of breast cancers are considered HER2-positive, which means that these cancerous cells overexpress binding human epidermal growth factor 2 (HER2). When HER2 receptors on cancer cells trap HER2, it signals uncontrolled reproduction of these cells. However, the opposite is also true: when HER2 + breast cancer cells are unable to bind to HER2, they die.

Tucatinib is a small molecule inhibitor of the HER2 growth factor receptor. The drug works by targeting the "tyrosine kinase" HER2 – a link in the communication chain that allows HER2 receptors to signal cell growth. Importantly, the fact that it is a small molecule means that the drug is able to cross the blood-brain barrier to act against the brain metastases of the disease. HER2 + breast cancer is more likely to affect younger women and also more likely than other breast cancers to specifically metastasize to the brain.

"One of the best things about this medication is that it combines well with almost everything. We tolerated that when you kill tucatinib in combination with other drugs, it's like if you just give the other medicine, it's a pill, it works, and it does not cause no side effects, it's really a doctor's dream. " As a result, tucatinib is evaluated in a number of other trials and with other partners, for example another trial offered at CU Cancer Center and elsewhere, exploring the use of the drug as a component of A combination against triple positive breast cancer (cancers expressing estrogen, progesterone and HER2 receptors). Borges hopes that the efficacy of tucatinib in patients with metastatic disease who have tried previous treatments may lead to trials of the drug used earlier during treatment.

In the present trial, tucatinib was combined with Ado-Trastuzumab Emtansine (T-DM1), which is part of a class of drugs known as antibody-drug conjugates. In this case, an antibody called trastuzumab that binds to HER2 is combined with a drug called emtansine that kills cells. Together, T-DM1 delivers the drug that kills cells directly to HER2-labeled cancer cells

"It's a diet without chemotherapy. Once the drug is approved, we hope to see this treatment appear during treatment Ultimately, we hope this will prevent recurrences and decrease the number of metastatic brain recurrences, "he says.

Updated findings will be presented at the Breast Cancer Symposium of San Antonio in December 2018.