Date: 2017-09-11
Type of
information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the European Society for Medical Oncology (ESMO) 2017 Congress
Company: Daiichi Sankyo (Japan)
Product: DS-8201a
Action
mechanism:
- antibody drug conjugate. DS-8201a is an investigational antibody drug conjugate comprised of a humanized anti-HER2 antibody attached by a peptide linker to a novel topoisomerase I inhibitor, utilizing Daiichi Sankyo’s proprietary payload and linker-payload technology. It is currently in phase 1 clinical development for HER2 expressing advanced or metastatic breast cancer or gastric cancer and other HER2 expressing solid cancers.
Disease: advanced/unresectable or metastatic breast cancer, gastric or gastroesophageal junction adenocarcinoma, or other solid tumors that is/are refractory to or intolerable with standard treatment or for which no standard treatment is available
Therapeutic
area: Cancer - Oncology
Country: Japan, USA
Trial
details:
- The DS-8201a Phase 1 Study is evaluating DS-8201a, given as an intravenous infusion every three weeks in patients with advanced/unresectable or metastatic breast cancer, gastric or gastroesophageal junction adenocarcinoma, or other solid tumors that is/are refractory to or intolerable with standard treatment or for which no standard treatment is available.
The primary objective of part 1 of the study (dose escalation) is to assess the safety and tolerability of DS-8201a and determine the maximum tolerated dose (MTD). Secondary objectives include evaluating the pharmacokinetics, efficacy and human anti-human antibody (HAHA) against DS-8201a.
The second part (dose expansion) of the ongoing phase 1 clinical trial is enrolling patients in Japan and the United States into one of four cohorts: patients with HER2+ breast cancer previously treated with T-DM1; patients with HER2+ gastric or gastroesophageal junction adenocarcinoma previously treated with trastuzumab; patients with HER2 low expressing breast cancer; and patients with other solid cancers that express HER2.
Latest
news:
- • On September 11, 2017, Daiichi Sankyo announced that DS-8201 demonstrated preliminary antitumor activity in patients with HER2-expressing solid tumors such as colon cancer, non-small cell lung cancer and other tumor types. These data were presented during a poster session at the European Society for Medical Oncology (ESMO) 2017 Congress. Preliminary results from this ongoing study showed that DS-8201 demonstrated an overall confirmed response rate of 32 percent and a disease control rate of 82 percent in a subgroup analysis of 22 of 25 evaluable patients with HER2-expressing solid tumors, which included colon cancer (11 patients), non-small cell lung cancer (6 patients), salivary gland cancer (4 patients), Paget’s disease (2 patients), cholangiocarcinoma (1 patient) and esophageal cancer (1 patient). Two of 10 evaluable patients with colon cancer, one out of five evaluable patients with non-small cell lung cancer and three of four evaluable patients with salivary gland cancer achieved partial responses. Two additional patients with colon cancer and non-small cell lung cancer with one post baseline scan showed a partial response yet to be confirmed at subsequent scans. A total of 168 patients have been treated in both the dose escalation (24 patients) and dose expansion (144 patients) parts of the study as of August 1, 2017.
- Safety data for 168 patients who received at least one dose of DS-8201 in study parts 1 and 2 and across different cohorts of the study also were reported. The most common adverse events (any grade) seen in all patients to date included nausea (67 percent), decreased appetite (56 percent), vomiting (33 percent), anemia (30 percent) and decreased platelet count (29 percent). Grade 3 adverse events occurring in >10 percent of patients included anemia (13 percent), decreased neutrophil count (14 percent) and decreased white blood cell count (11 percent). Grade 4 adverse events occurred in ? 3 percent of patients and included decreased platelet count (3.0 percent), decreased neutrophil count (2.4 percent), decreased white blood cell count (1.8 percent) and anemia (1.2 percent).
A pivotal phase 2 study of DS-8201 in HER2-positive metastatic breast cancer is ongoing and Daiichi Sankyo is exploring next steps for the development of this compound across multiple HER2-expressing tumor types.
• On October 9, 2016, Daiichi Sankyo announced safety and preliminary efficacy data from a phase 1 study of DS-8201a, a novel investigational HER2-targeting antibody drug conjugate, which suggest that it was well-tolerated with no dose-limiting toxicities. These results, from the dose escalation part of a two-part phase 1 study of DS-8201a, will be presented today during a late-breaking poster discussion session at the ESMO 2016 Congress, the annual meeting of the European Society for Medical Oncology (ESMO). Preliminary overall efficacy results in 20 evaluable patients demonstrated an objective response rate of 35 percent (seven partial responses) and disease control rate of 90 percent, including 12 patients previously treated with ado-trastuzumab emtansine (T-DM1) and five patients with HER2 low expression (IHC2+/FISH- or IHC1+). In 15 patients with HER2+ disease defined as IHC3+ or IHC2+/FISH+, the disease control rate was 100 percent. Seventeen patients are still on treatment, and five of the first 10 patients have been under active treatment (0.8 to 6.4 mg/kg) for more than 24 weeks. Median progression free survival has not been reached.
A total of 22 patients (16 breast cancer, 5 gastric cancer, 1 gastroesphageal junction adenocarcinoma) were treated in the dose escalation part of the study. The maximum tolerated dose was not reached (0.8-8.0 mg/kg given every three weeks) and there have been no dose-limiting toxicities at pharmacologically-active exposure and a favorable pharmacokinetic profile. Seven grade 3 adverse events were seen in three patients (1 hypokalemia, 1 anemia, 1 neutrophil count decreased, 2 lymphocyte count decrease, 1 ALP increase and 1 cholangitis). Most common adverse events were mild or moderate gastrointestinal and hematological events.
HER2+ Breast Cancer Subgroup Analyses: A total of 18 patients enrolled in the study received one or more prior anti-HER2 therapies (18 received trastuzumab, 13 ado-trastuzumab emtansine, 5 pertuzumab, 4 lapatinib). In 12 evaluable HER2+ breast cancer patients previously treated with ado-tratuzumab emtansine (T-DM1), the objective response rate was 42 percent with a disease control rate of 92 percent.
- • On September 28, 2016, Daiichi Sankyo announced that safety and preliminary efficacy phase 1 data evaluating DS-8201a, a novel HER2-targeting antibody drug conjugate, will be presented during a late-breaking poster discussion session during the European Society for Medical Oncology (ESMO) 2016 Congress from October 7 -11 in Copenhagen, Denmark.
LBA17: Single Agent Activity of DS-8201a, a HER2-Targeting Antibody-Drug Conjugate, in Breast Cancer Patients Previously Treated with T-DM1: Phase 1 Dose Escalation
Results from part 1 (dose escalation) of a two-part phase 1 study of DS-8201a by Kenji Tamura, MD, PhD, Chairman, Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo will be presented on Sunday, October 9 at 4:30 pm CEST. The primary objective of the dose escalation part of the study was to examine the safety and tolerability of DS-8201a along with determining the maximum tolerated dose. Secondary objectives include evaluating the pharmacokinetics and efficacy of DS-8201a. Additional sub-group analyses of preliminary efficacy of DS-8201a in advanced or metastatic breast cancer patients previously treated with ado-trastuzumab emtansine (T-DM1) will be presented.
- The second part (dose expansion) of the phase 1 clinical trial evaluating the safety and efficacy of DS-8201a is currently underway, and will enroll patients in the United States and Japan into one of four treatment cohorts: patients with HER2+ breast cancer previously treated with T-DM1; patients with HER2+ gastric or gastroesphageal junction adenocarcinoma previously treated with trastuzumab; patients with HER2-low expressing breast cancer; and, patients with other solid cancers that express HER2.
Is
general: Yes
