AstraZeneca and Daiichi Sankyo presented positive data from their Phase II single-arm DESTINY-Breast01 trial of trastuzumab deruxtecan (DS-8201) in HER2-positive metastatic breast cancer patients who received two or more previous HER-2 targeted regimens.
AstraZeneca and Daiichi Sankyo presented positive data from their Phase II single-arm DESTINY-Breast01 trial of trastuzumab deruxtecan (DS-8201) in HER2-positive metastatic breast cancer patients who received two or more previous HER-2 targeted regimens. The objective response rate (ORR), which was the primary endpoint, was 60.9% with the drug alone.
These patients had already undergone about six previous treatments. On the trastuzumab treatment, they showed no further disease progression for a median of 16.4 months. Typically, this patient group’s health would continue to deteriorate after approximately six months.
“This is a totally unprecedented clinical benefit,” Jose Baselga, AstraZeneca’s executive vice president of Oncology R&D, told Reuters.
In a statement, Baselga said, “The clinically meaningful and durable responses seen among these patients illustrate the potential of trastuzumab deruxtecan to establish a new standard of care. These results are impressive, as women with this advanced stage of breast cancer have already endured multiple prior therapies for HER2-positive metastatic breast cancer.”
HER2 is a tyrosine kinase receptor growth-promoting protein. It is generally associated with aggressive cancer and poor prognosis in breast cancer.
Trastuzumab deruxtecan is the lead product in the antibody drug conjugate (ADC) franchise of the Daiichi Sankyo Cancer Enterprise as well as the most advanced program in AstraZeneca’s ADC platform. ADCs use an antibody to more precisely deliver a chemotherapy drug to cancer cells. AstraZeneca and Daiichi Sankyo entered into the collaboration in March 2019. It is a global deal, except in Japan where Daiichi Sankyo holds exclusive rights. Under the agreement, AstraZeneca could pay up to $6.9 billion to Daiichi.
In the trial, patients hit a disease control rate (DCR) of 97.3% with a median duration of response (DoR) of 14.8 months. There was a median progression-free survival (PFS) of 16.4 months. The median overall survival (OS) hasn’t been met yet, with an estimated survival rate of 86% at one year.
DESTINY-Breast01 is the first of a planned 28 clinical trials with trastuzumab deruxtecan. Other studies will investigate breast cancer in earlier treatment periods, as well as in lung and gastric cancer.
The companies have already applied for approval with the U.S. Food and Drug Administration (FDA).
“These results are particularly striking as trastuzumab deruxtecan prompted a high level of durable tumor reduction among patients, the majority of whom had exhausted most if not all standard therapies for HER2-metastatic breast cancer,” said Ian E. Krop, principal investigator of the trial and associate chief, Division of Breast Oncology, Susan F. Smith Center for Women’s Cancers, Dana-Farber Cancer Institute. “We are excited by these results and their potential to help patients with this advanced stage of breast cancer.”
Safety and tolerability of the drug was consistent with that seen in the Phase I clinical trial. The most common Grade 3 or higher adverse events related to treatment were decreased neutrophil count, anemia, nausea, decreased white cell count, decreased lymphocyte count and fatigues. About 13.6% of patients had confirmed interstitial lung disease (ILD) related to treatment. Four deaths were associated with ILD. ILD is a broad group of disorders that cause scarring, or fibrosis, of the lungs.
