Daiichi Sankyo presents updated data for DS-8201 in patients with HER2-expressing breast cancer at SABC symposium

Daiichi Sankyo Company, Limited has announced that updated safety and efficacy data from two subgroups of patients with metastatic breast cancer from an ongoing phase 1 study of DS-8201, an investigational HER2-targeting antibody drug conjugate (ADC), were presented during a Spotlight Poster Discussion session at the 2017 San Antonio Breast Cancer (SABC) symposium.

Updated preliminary results in a subgroup analysis of 57 efficacy evaluable patients with HER2-positive metastatic breast cancer pre-treated with ado-trastuzumab emtansine (T-DM1) showed that DS-8201 demonstrated a confirmed overall response rate of 61.4 per cent (35 of 57 patients) and a disease control rate of 94.7 per cent (54 of 57 patients). Among 50 of these patients who also were pre-treated with pertuzumab, DS-8201 demonstrated a confirmed overall response rate of 62 per cent (31 of 50 patients) and a disease control rate of 94 per cent (47 of 50 patients). In 39 efficacy evaluable HER2-positive patients with hormone-receptor positive disease, DS-8201 demonstrated an overall response rate of 56.4 per cent (22 of 39 patients) and disease control rate of 92.3 per cent (36 of 39 patients). The majority of patients with HER2-positive metastatic breast cancer were continuing to receive treatment at the time of data cut-off. Preliminary estimates of median progression free survival have reached 10.4 months.

Additionally, preliminary results in another subgroup showed that DS-8201 demonstrated a confirmed overall response rate of 31.6 per cent (6 of 19 patients) and a disease control rate of 84.2 per cent (16 of 19 patients) in 19 efficacy evaluable patients with heavily pretreated HER2 low-expressing breast cancer (defined as IHC2+/ISH- or IHC 1+). In 16 of these patients also classified with hormone-receptor positive disease, DS-8201 demonstrated an overall response rate of 31.3 per cent (5 of 16 patients) and a disease control rate of 87.5 per cent (14 of 16 patients). Most patients with HER2 low-expressing breast cancer were continuing to receive treatment at the time of data cut-off. Median progression free survival has not yet been reached.

“These updated data in HER2-positive metastatic breast cancer are exciting in that DS-8201 is showing potential in treating patients who have progressed on several other HER2-targeting agents,” said Shanu Modi, MD, Breast Medical Oncologist, Memorial Sloan Kettering Cancer Center and study investigator. “Additionally, the results seen in patients with HER2 low-expressing breast cancer are compelling and could challenge how we define HER2-positive breast cancer with regards to ADC therapy. Clearly, further study of DS-8201 is warranted in both these types of HER2-expressing breast cancer.”

These data add to the growing evidence that underscore the potential of our smart chemotherapy DS-8201 to treat HER2-expressing breast cancer,” said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. “While we already have advanced DS-8201 into a pivotal phase 2 trial for HER2-positive metastatic breast cancer, we are exploring next steps for the development of DS-8201 in HER2 low-expressing breast cancer.” 

Combined preliminary safety data for both HER2 low-expressing and HER2-positive breast cancer subgroups were reported. The most common adverse events (>30 per cent any grade) included nausea (73.0 per cent), decreased appetite (55.7 per cent), alopecia (40.0 per cent), vomiting (39.1 per cent), anaemia (34.8 per cent), diarrhoea (33.9 percent) and constipation (30.4 per cent). Grade 3 adverse events occurring in >10 per cent of patients included decreased neutrophil count (10.4 per cent) and decreased white blood cell count (10.4 per cent). Grade 4 adverse events included decreased neutrophil count (4.3 per cent), decreased platelet count (2.6 per cent) and anaemia (0.9 per cent). Two cases of potential Grade 5 pneumonitis have been reported and will be assessed by an interstitial lung disease (ILD) adjudication committee.

Unmet Need in HER2-Expressing Metastatic Breast Cancer

About one in five breast cancers overexpress HER2, a tyrosine kinase receptor growth-promoting protein found on the surface of some cancer cells, which is associated with aggressive disease.1  To be considered HER2-positive, tumor cancer cells are usually tested by one of two methods: immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH).1 IHC test results are reported as: 0, IHC1+, IHC2+ or IHC3+.1 A finding of IHC3+ is considered HER2-positive.1  A finding of IHC2+ is borderline and typically is confirmed by a positive FISH test.1

Several unmet needs remain today in HER2-expressing metastatic breast cancer. Many tumors advance to the point where no currently approved HER2-targeting treatment continues to control the disease, and there is no current standard of care for HER2-positive tumors after treatment with trastuzumab, pertuzumab and T-DM1.2 Additionally, there are no anti-HER2 therapies indicated for HER2 low-expressing tumors (IHC2+/FISH- or IHC1+).

Unresectable or metastatic solid tumors that are refractory or intolerant to standard treatment, or for whom no standard treatment is available. The primary objective of the dose escalation phase of the study was to assess the safety and tolerability of DS-8201 and determine the maximum tolerated dose. In the dose expansion part of the phase 1 study, DS-8201 is given in one of two doses (5.4 mg/kg and 6.4 mg/kg) to patients with HER2-positive advanced or metastatic breast cancer and gastric cancer, HER2 low-expressing breast cancer and other HER2-expressing solid tumors. Patient enrollment in the two breast cancer cohorts and the HER2-expressing solid tumors cohort is ongoing in the U.S. and Japan.