Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) today announced that updated phase 1 safety and efficacy data for DS-8201, an investigational HER2-targeting antibody drug conjugate (ADC), in a subgroup of patients with HER2-expressing gastric cancer previously treated with trastuzumab and chemotherapy were presented during a poster session at the 2018 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium in San Francisco, California.
Updated preliminary subgroup analysis results in 44 of 45 efficacy evaluable patients with HER2-expressing gastric cancer or gastroesophageal junction adenocarcinoma previously treated with trastuzumab and chemotherapy showed that DS-8201 demonstrated a confirmed overall response rate of 45.5 percent (20 of 44 patients) and a disease control rate of  81.8 percent (36 of 44 patients). Median duration of response was 7.0 months (95 percent CI: NR). The Kaplan-Meier estimate of median progression-free survival was 5.8 months (95 percent CI: 3.0, 8.3). A total of 17 out of 44 patients were continuing to receive treatment at the time of data cut-off.
“Gastric cancer can be difficult to treat due to its molecular complexity, and currently there are no HER2- targeted therapies or antibody drug conjugates approved for HER2-positive advanced gastric cancer that progresses following treatment with trastuzumab,” said Toshihiko Doi, MD, PhD, Department of Experimental Therapeutics, National Cancer Center Hospital East. “These phase 1 results are encouraging and demonstrate the importance of continuing to study the potential of DS-8201 in treating HER2-positive gastric cancer. The pivotal phase 2 study is currently underway.”
A subgroup analysis of 23 patients previously treated with CPT-11 (irinotecan) showed that DS-8201 demonstrated a confirmed overall response rate of 43.5 percent (10 of 23 patients) and a disease control rate of 82.6 percent (19 of 23 patients). Median duration of response was 6.9 months (95 percent CI: NR). The Kaplan-Meier estimate of median progression-free survival for this subgroup of patients was 4.1 months (95 percent CI: 2.5, 8.3).
“These data from patients with HER2-positive gastric cancer who have failed HER2-targeted therapy combined with chemotherapy, and for many who also failed irinotecan as a systemic chemotherapy suggest that the ADC technology of DS-8201 appears able to deliver on what it was specifically researched and innovated for: a smart chemotherapy approach to tumors expressing some degree of HER2 receptors, regardless of prior treatment with a topoisomerase I inhibitor,” said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. “A comprehensive translational research effort is planned and underway to further understand the biological basis for the observed activity, including the role of tumor heterogeneity and HER2 expression, the mechanisms of resistance that may have contributed to failing prior lines of treatment, and factors more directly related to the unique pharmacological profile of DS-8201.”
Updated preliminary safety data for this subgroup of trastuzumab-treated HER2-expressing gastric cancer patients were also reported. The most common adverse events (>30 percent, any grade) included nausea (71.1 percent), decreased appetite (64.4 percent), platelet count decreased (33.3 percent), white blood cell count decreased (33.3 percent) and constipation (31.1 percent). Grade 3 adverse events occurring in >10 percent of patients included anemia (24.4 percent), neutrophil count decreased (15.6 percent), platelet count decreased (13.3 percent) and white blood cell count decreased (11.1 percent). Grade 4 adverse events included platelet count decreased (4.4 percent), white blood cell count decreased (4.4 percent) and neutrophil count decreased (4.4 percent). Three patients discontinued treatment due to treatment-emergent adverse events (pneumonia, decreased appetite, and pneumonitis). Two potential cases of interstitial lung disease (ILD) were reported by the investigators (one grade 1 and one grade 3) in gastric cancer subjects and together with all reported or suspected ILD cases are being assessed by an independent ILD adjudication committee. These include two cases of potential Grade 5 pneumonitis previously reported in the breast cancer cohorts.
Based on these phase 1 data, patients are currently being enrolled in the pivotal, phase 2 open-label DESTINY-Gastric01 study investigating the safety and efficacy of DS-8201 in patients with HER2-positive advanced gastric cancer or gastroesophageal junction adenocarcinoma (defined as IHC3+ or IHC2+/ISH+) who have progressed on two prior regimens including fluoropyrimidine agent, platinum agent and trastuzumab.