Preliminary exploratory efficacy results from an ongoing phase 1 dose escalation study showed that an overall response rate of 58.8 percent was observed with single agent DS-3201 in 17 evaluable patients with NHLs, including B-cell and T-cell lymphomas, who were relapsed from or refractory to standard treatment or for whom no standard treatment was available.
- Preliminary exploratory efficacy results from phase 1 study show an overall response rate of 58.8 percent with single agent DS-3201, an investigational and potential first-in-class EZH1/2 dual inhibitor, in patients with relapsed or refractory non-Hodgkin lymphomas
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| [11-December-2017] |
| TOKYO and BASKING RIDGE, N.J. and MUNICH, Dec. 11, 2017 /PRNewswire/ -- Daiichi Sankyo today announced that preliminary safety and efficacy data from a phase 1 study of DS-3201, an investigational and potential first-in-class EZH1/2 dual inhibitor, in patients with relapsed or refractory non-Hodgkin lymphomas (NHLs) were presented during a poster session at the 59th Annual Meeting of the American Society of Hematology in Atlanta, Georgia. Preliminary exploratory efficacy results from an ongoing phase 1 dose escalation study showed that an overall response rate of 58.8 percent (10 of 17 patients) was observed with single agent DS-3201 in 17 evaluable patients with NHLs, including B-cell and T-cell lymphomas, who were relapsed from or refractory to standard treatment or for whom no standard treatment was available. Among the 10 patients with response, there were one complete remission and nine partial remissions. Additionally, four patients experienced stable disease and three patients experienced progressive disease. An overall response rate of 45.5 percent (5 of 11 patients) was observed with DS-3201 in 11 evaluable patients with B-cell lymphomas, including follicular lymphoma (5 patients), diffuse large B-cell lymphoma (3 patients), extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (2 patients) and lymphoplasmacytic lymphoma (1 patient). An overall response rate of 83.3 percent (5 of 6 patients) was observed with DS-3201 in six evaluable patients with T-cell lymphomas, including peripheral T-cell lymphoma not otherwise specified (2 patients), angioimmunoblastic T-cell lymphoma (2 patients) and adult T-cell leukemia-lymphoma (2 patients). “Based on these preliminary safety and efficacy data on DS-3201 in a clinical setting, further evaluation of DS-3201 is warranted,” said Dai Maruyama, MD, PhD, Department of Hematology, National Cancer Center Hospital, Tokyo, Japan. “As the first dual inhibitor of EZH1 and EZH2 in clinical development, DS-3201 may represent a new epigenetic approach to treating blood cancers. We look forward to reviewing additional data as it becomes available to evaluate the potential of this approach.” Following observation of dose-limiting toxicities (DLTs) in three of 18 evaluable patients, dose expansion is ongoing to determine a conclusive recommended phase 2 dose. Four DLTs were observed in three patients who received either the 200 mg or 300 mg dose: there were three cases of temporary grade 4 platelet count decreases (one patient in the 200 mg cohort and two patients in the 300 mg cohort) and one case of grade 3 anemia requiring transfusion in a patient in the 300 mg cohort. Preliminary safety data from 18 evaluable patients in the study also were reported. The most common treatment emergent hematologic adverse events of any grade seen in all patients included decreased platelet count (77.8 percent), anemia (55.6 percent), decreased lymphocyte count (50.0 percent) and decreased neutrophil count (44.4 percent). The most common treatment emergent non-hematologic adverse events were dysgeusia (50.0 percent), alopecia (33.3 percent), diarrhea (22.2 percent), decreased appetite (22.2 percent), nasopharyngitis (22.2 percent), alanine aminotransferase increased (22.2 percent), rash (16.7 percent), aspartate aminotransferase increased (16.7 percent) and dry skin (16.7 percent). One serious adverse event of grade 3 pneumocystis jirovecii pneumonia (PJP) led to discontinuation from the study. There was one additional non-serious case of PJP observed, leading to the institution of prophylactic treatment for all subsequent patients enrolled into the study. DS-3201 targets epigenetic regulation by inhibiting both the EZH1 (enhancer of zeste homolog 1) and EZH2 (enhancer of zeste homolog 2) enzymes, which may reactivate various genes that have been silenced by the protein H3K27me3.1 Reactivation of the silenced genes has been shown to result in decreased proliferation of EZH2-expressing cancer cells. Preclinical research has shown that DS-3201 suppressed trimethylation of H3K27 in cells (IC50: 0.55 nM) more potently than EZH2 selective inhibitors.1 “Targeting epigenetic regulation is an approach to treating cancer that aims to reverse aberrant epigenetic changes that contribute to cancer cell growth and to maintain normal gene expression. The dual inhibition of EZH1/2 is theoretically able to provide a different spectrum of activity compared to EZH2-specific inhibitors already in the clinic. Our phase 1 program is designed to address the question of the potential benefit for this dual mode of action,” said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. “In addition to the phase 1 study in non-Hodgkin lymphomas, we also are evaluating targeting epigenetic regulation with DS-3201 in patients with acute myeloid leukemia and acute lymphocytic leukemia.” About Non-Hodgkin Lymphoma About the DS-3201 Phase 1 Study About DS-3201 About Daiichi Sankyo Cancer Enterprise About Daiichi Sankyo Contact References
SOURCE Daiichi Sankyo Company, Limited |
