# TK216

Source: https://onco.cc/drugs/tk216/  
OnCo record `tk216` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

TK216 was an attempt to hit the fusion protein that causes Ewing sarcoma directly, something long thought impossible for a transcription factor. In early trials with vincristine it produced a few responses but not enough to carry the drug forward.

## Summary

TK216 was Oncternal Therapeutics' first-in-class small molecule aimed at EWS-FLI1, the fusion transcription factor present in about 85 percent of Ewing sarcomas. It was given as a continuous intravenous infusion, alone and with vincristine, in a phase 1/2 trial in relapsed or refractory Ewing sarcoma. A minority of heavily pretreated patients had objective responses, including some complete responses, but the response rate did not meet the threshold for a registrational study and the sponsor did not continue development.

The Ewing sarcoma page names it with IGF-1R antibodies and PARP inhibitors among the targeted approaches that have not yet succeeded, while lurbinectedin and combinations remain in trials.

## Fields

- Kind: Treatment
- Status: phase-2
- Last checked: 2026-09-17
- Also known as: TK-216
- Tags: subtype-drugs-wave
- Code: TK216
- Modality: Small-molecule EWS-FLI1 inhibitor
- Mechanism: Designed from the YK-4-279 series to bind the EWS-FLI1 fusion oncoprotein and prevent its interaction with RNA helicase A, disabling the transcription factor that drives Ewing sarcoma; it also disrupts microtubules.

## Connected records

- drugs: [Lurbinectedin](https://onco.cc/drugs/lurbinectedin/), [Vincristine](https://onco.cc/drugs/vincristine/)
- cancers: [Ewing sarcoma](https://onco.cc/cancers/ewing-sarcoma/)
- targets: [EWSR1-FLI1 fusion](https://onco.cc/targets/ewsr1-fli1/)
- companies: [Oncternal Therapeutics](https://onco.cc/companies/oncternal-therapeutics/)

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JSON: https://onco.cc/api/v1/entities/tk216.json