AstraZeneca is starting a collaboration with Daiichi Sankyo for the global production and commercialization of trastuzumab deruxtecan (DS-8201), a novel antibody-drug conjugate under clinical studies for the treatment of advanced HER2-positive breast cancer, and other types of solid tumors.
The investigational therapy was granted fast track status by the U.S. Food and Drug Administration (FDA) in 2016, and gained breakthrough therapy designation in 2017, for patients with HER2-positive, locally advanced or metastatic breast cancers that progressed after prior HER2 therapies, including Kadcyla (ado-trastuzumab emtansine).
Early results from a pivotal Phase 1 clinical trial (NCT02564900), still underway, show that treatment with trastuzumab deruxtecan has a “strong activity in a number of tumor types,” Astrazeneca stated in a press release.
Of note, the magnitude and duration of response was highest in patients with HER2-positive metastatic breast cancer who have progressed after prior treatment with Kadcyla. In these patients, overall response rate was 64.2%, meaning that the tumors shrunk at least partially in 43 of 67 patients. The response lasted a median of 7.6 months.
Trastuzumab deruxtecan is an antibody-conjugated drug, composed of an approved anticancer HER2-targeting antibody (trastuzumab, brand name Herceptin) linked to an investigational cancer-killing agent (an exatecan derivative, deruxtecan).
The product was designed so that trastuzumab helps deliver deruxtecan specifically to HER2-expressing cancers, improving cancer specificity and reducing off-targets, when compared with conventional chemotherapy.
A broad development program is underway in North America, Europe, and Asia, including five pivotal trials in HER2-expressing breast and gastric cancers, including cancers with low HER2 expression.
AstraZeneca and Daiichi Sankyo have plans to initiate submissions to gain approval for patients with advanced or difficult-to-treat breast cancer in the second half of this year.
In addition, other clinical trials are evaluating the treatment for HER2-expressing colorectal cancer and non-small cell lung cancer (NSCLC) and in combination with Opdivo (nivolumab) for HER2-expressing metastatic breast and bladder cancers.
Under the agreement reached between Daiichi Sankyo and AstraZeneca, both companies will join efforts to accelerate the development of the potential therapy worldwide. Daiichi Sankyo will be solely responsible for manufacturing and supplying the product except in Japan, where it will maintain exclusive marketing rights.
“We believe that trastuzumab deruxtecan could become a transformative new medicine for the treatment of HER2–positive breast and gastric cancers. In addition, it has the potential to redefine breast cancer treatment as the first therapy for HER2-low expressing tumours,” said Pascal Soriot, AstraZeneca’s CEO.
“By aiming to provide new treatment options across a wide range of cancers as soon as possible, we will maximise our contribution to patients with cancer and their families around the world,” George Nakayama, representative director, chairman and CEO of Daiichi Sankyo said.