Sumitomo Dainippon Pharma Oncology Presents Findings from Phase 1 Clinical Study Evaluating Investigational Agent Dubermatinib in Patients with Advanced Solid Tumors at ESMO 2020 Virtual Annual Congress

CAMBRIDGE, Mass., Sept. 18, 2020 /PRNewswire/ -- Sumitomo Dainippon Pharma Oncology, Inc., a developer of novel cancer therapeutics, today presented new data from the ongoing Phase 1 study evaluating dubermatinib (TP-0903), an AXL kinase inhibitor, in patients with advanced solid tumors. These results were presented during a mini-oral presentation at the European Society of Medical Oncology (ESMO) 2020 Virtual Annual Congress, being held September 19- 21, 2020.

Preliminary findings from the Phase 1a/b first-in-human, open-label, dose-escalation, safety, pharmacokinetics and pharmacodynamic study indicated dubermatinib was well tolerated with a manageable safety profile as a monotherapy or in combination with immunotherapy or tyrosine kinase inhibitor (TKI). Dubermatinib, as a single agent and as part of the combination regimens, showed preliminary signs of clinical activity in the study, with four partial responses observed.1

The study consists of two parts. The dose escalation portion of the study enrolled 45 patients with advanced solid tumors across 10 dose levels of dubermatinib monotherapy. The expansion portion of the study enrolled 132 patients across five cohorts of various solid tumor types, including combination cohorts receiving dubermatinib plus immunotherapy or dubermatinib plus TKI.1 In the dose escalation portion of the study, 5% (n=2 of 45) of patients achieved a partial response when treated with dubermatinib monotherapy (1 patient with metastatic melanoma and 1 patient with intrahepatic cholangiocarcinoma) and 29% (n=13 of 45) of patients experienced stable disease, resulting in an overall disease control rate of 33%.1

In the expansion portion of the study, 5% (n=1 of 21) of patients in Cohort A (one patient with non-small cell lung cancer treated with dubermatinib plus immunotherapy) and 5% (n=1 of 22) of patients in Cohort B (one patient with non-small cell lung cancer treated with dubermatinib plus TKI) achieved a partial response. Across cohorts, 14-48% of patients experienced stable disease and a disease control rate ranging from 14-53% was achieved. In Cohort C (patients with colorectal cancer treated with dubermatinib monotherapy), pharmacodynamic evaluation of pre- and post-treatment tumor biopsies and peripheral blood mononuclear cells correlated with clinical activity.1

The maximum tolerated dose of dubermatinib was determined to be 50 mg. The most frequently observed treatment-emergent adverse events of Grade 3 or higher at least possibly related to dubermatinib were nausea, vomiting and diarrhea.1

“These preliminary data presented at ESMO 2020 are encouraging as we learn more about how dubermatinib may inhibit the AXL kinase protein and sensitize cancer cells to treatment with other targeted agents in patients with advanced solid tumors,” said David J. Bearss, Ph.D., Chief Scientific Officer and Global Head of Research, Sumitomo Dainippon Pharma Oncology (SDP Oncology). “We are continuing to advance this study to evaluate the potential role of dubermatinib in immune cell modulation by observing changes in the tumor immune microenvironment in patients with specific tumor types.” Below are the details for the SDP Oncology presentation:

Abstract Title Details Presenter
A Phase 1, First-in-human, Safety, Pharmacokinetic, and Pharmacodynamic Study of Oral Dubermatinib (TP-0903) in
Patients with Advanced Solid Tumors
Presentation #536MO
Friday, September 18 at 9:56 a.m. CEST Mini-Oral Presentation
John Sarantopoulos, M.D., UT Health
San Antonio

About Dubermatinib (TP-0903)

Dubermatinib is an investigational oral AXL receptor tyrosine kinase (RTK) inhibitor under evaluation in a Phase 1a/b study in patients with advanced solid tumors (NCT02729298) and an ongoing study in collaboration with the Leukemia & Lymphoma Society as part of the Beat AML Clinical Trial (NCT03013998). SDP Oncology is exploring parallel clinical development paths for dubermatinib in both solid and hematologic malignancies.

About AXL Kinase

AXL belongs to the TAM (Tyro3, AXL and Mer) family of receptor tyrosine kinases and is overexpressed in many human cancers.1 It plays a key role in tumor cell proliferation, survival, metastasis, cellular adhesion, and avoidance of the immune response. The overexpression of AXL is associated with a poor patient prognosis and drug resistance.2

About Sumitomo Dainippon Pharma Oncology

Sumitomo Dainippon Pharma Oncology, Inc., is a wholly owned subsidiary of Sumitomo Dainippon Pharma Co., Ltd. As a global oncology organization with teams in the U.S. and Japan, SDP Oncology is relentlessly committed to advancing purposeful science by transforming new discoveries into meaningful treatments for patients with cancer. The company's robust and diverse pipeline of preclinical and advanced-stage assets spans multiple areas, including oncogenic pathways, survival mechanisms and novel protein interactions, which aim to address unmet clinical needs in oncology.

For more information, visit www.sdponcology.com.

About Sumitomo Dainippon Pharma

Sumitomo Dainippon Pharma is among the top-10 listed pharmaceutical companies in Japan, operating globally in major pharmaceutical markets, including Japan, the U.S., China and the European Union. Sumitomo Dainippon Pharma aims to create innovative pharmaceutical products in the Psychiatry & Neurology area, the Oncology area and Regenerative medicine/Cell therapy field, which have been designated as the focus therapeutic areas. Sumitomo Dainippon Pharma is based on the merger in 2005 between Dainippon Pharmaceutical Co., Ltd., and Sumitomo Pharmaceuticals Co., Ltd. Today, Sumitomo Dainippon Pharma has more than 6,000 employees worldwide. Additional information about Sumitomo Dainippon Pharma is available through its corporate website at www.ds-pharma.com.

Disclaimer Regarding Forward-Looking Statements

This press release contains "forward-looking statements," as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. The forward-looking statements in this press release are based on management's assumptions and beliefs in light of information presently available and involve both known and unknown risks and uncertainties. Any forward-looking statements set forth in this press release speak only as of the date of this press release. We do not undertake to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. Information concerning pharmaceuticals (including compounds under development) contained within this material is not intended as advertising or medical advice.

References

1 Adjei, A, Beg, M, Melear, J, et al. A Phase 1, First-in-human, Safety, Pharmacokinetic, and Pharmacodynamic Study of Oral Dubermatinib (TP-0903) in Patients with Advanced Solid Tumors. European Society of Medical Oncology (ESMO) 2020 Virtual Annual Congress. 18 September 2020. Presentation 536MO.

2 Soh KK, Bahr BL, Bearss JJ, et al. Inhibition of Axl kinase reverses the mesenchymal phenotype in leukemic cells through the disruption of retinoic signaling [Abstract]. Blood. 2015;126:3253.

3 Park IK, Mundy-Bosse B, Whitman SP, et al. Receptor tyrosine kinase Axl is required for resistance of leukemic cells to FLT3-targeted therapy in acute myeloid leukemia. Leukemia. 2015;29(12):2382-2389.

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