On September 18, 2020 Sumitomo Dainippon Pharma Oncology, Inc., a developer of novel cancer therapeutics, reported new data from the ongoing Phase 1 study evaluating dubermatinib (TP-0903), an AXL kinase inhibitor, in patients with advanced solid tumors (Press release, Sumitomo Dainippon Pharma, SEP 18, 2020, View Source [SID1234565367]). These results were presented during a mini-oral presentation at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2020 Virtual Annual Congress, being held September 19-21, 2020.

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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 (Free ESMO Whitepaper) 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.2 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.3