20 September 2019 - - Paul A. Meyers, M.D., chief, Pediatric Sarcoma Service and vice chair for Clinical Affairs of Memorial Sloan Kettering Cancer Center, presented a case study of a patient with Ewing sarcoma who achieved a sustained response following treatment with US-based biopharmaceutical company Oncternal Therapeutics, Inc.'s (NASDAQ: ONCT) investigational product candidate, TK216, in an ongoing Phase 1, first-in-human clinical trial, the company said.

The presentation entitled, "TK216 for the Treatment of Ewing Sarcoma," was given at the Fall Children's Oncology Group Meeting.

Dr. Meyers reported that the patient, who had a history of Ewing sarcoma with pulmonary metastases, had recurrent disease despite multiple courses of chemotherapy, radiation, bevacizumab, pazopanib and surgery.

Following two cycles of TK216 therapy given as a single agent, the patient achieved a confirmed objective response, which included resolution of several pulmonary lesions.

This response has been sustained and has continued at six months of treatment, with the patient receiving TK216 plus vincristine in subsequent treatment courses.

The final remaining residual tumor nodule which was less than one centimeter in diameter was later surgically removed, leading to a surgical complete remission. Treatment with TK216 has been well-tolerated by this patient.

TK216 is an investigational, potentially first-in-class small molecule that is designed to inhibit the biological activity of E26 transformation-specific transcription factor oncoproteins including fusion proteins.

Tumorigenic gene fusions involving ETS factors are frequently found in tumors such as Ewing sarcoma and prostate cancer, and ETS factors are often overexpressed in other tumors such as prostate cancer, and acute myeloid leukemia.

TK216 was developed based on discoveries of Jeffrey Toretsky, M.D. and his team at Georgetown University, who found inhibitors of EWS-FLI1 using a novel chemical screening assay.

In preclinical models, TK216 binds to EWS-FLI1 and blocks the interaction between ETS family members and RNA helicase A leading to tumor cell apoptosis.

TK216 is being evaluated in a Phase 1 clinical study as a single agent and in combination with vincristine in patients with relapsed or refractory Ewing sarcoma, a rare pediatric cancer that has historically been very challenging to treat effectively, particularly for recurrent and metastatic disease.

A dose-finding arm of this study is nearing completion, after which Oncternal intends to begin enrolling patients in an expansion cohort of the study to evaluate the clinical response of treatment with TK216 in combination with vincristine, an approved chemotherapy agent.

This multi-center study is actively enrolling patients at six clinical trial centers across the US Additional information about the TK216 study may be accessed at ClinicalTrials.gov (NCT02657005).

Oncternal Therapeutics is a clinical-stage biopharmaceutical company focused on developing product candidates for the treatment of cancers with critical unmet medical need.

Oncternal focuses drug development on promising yet untapped biological pathways implicated in cancer generation or progression.

The pipeline includes cirmtuzumab, a monoclonal antibody designed to inhibit the ROR1 receptor, a type I tyrosine kinase-like orphan receptor that is expressed by many cancers but not by normal tissues and is associated with cancer stemness, that is being evaluated in a Phase 1/2 clinical trial in combination with ibrutinib for the treatment of chronic lymphocytic leukemia and mantle cell lymphoma, and TK216, a small-molecule compound that is designed to inhibit E26 transformation specific family oncoproteins, which is being evaluated in a Phase 1 clinical trial for patients with Ewing sarcoma alone and in combination with vincristine chemotherapy.

In addition, Oncternal has a CAR-T product candidate that targets ROR1, which is currently in preclinical development as a potential treatment for hematologic cancers and solid tumors.