Proffered Paper - Sarcoma Proffered Paper session

1620O - Phase I study of TK216, a novel anti-ETS agent for Ewing sarcoma

Presentation Number
Lecture Time
17:16 - 17:28
  • Joseph A. Ludwig (Houston, AL, United States of America)
Channel 1
16:20 - 18:00



Ewing Sarcoma (ES) is a rare pediatric cancer with poor prognosis and high unmet need. Chimeric oncoproteins encoded by fusions of the EWS gene and one of five different ETS transcription factors are dominant drivers of the disease. TK216 was designed to bind ETS proteins directly, disrupt protein interactions, inhibit transcription factor function and cause apoptotic cell death. Notably, TK216 plus vincristine (VCR) was shown to exert synergistic activity (Zollner 2017). Here, we report the results of the phase I trial of TK216 in ES.


TK216 was administered by continuous IV infusion to adult and pediatric patients (pts) with relapsed / refractory ES in a phase I study using a 3+3 design. Dosing duration of 7 days was later extended to 10 and 14 days, with a 14-day break to complete a cycle (C). DLT was evaluated during C1, and efficacy was evaluated after completion of C2. VCR could be added to treatment after C2.


32 pts were enrolled into 9 dose and schedule escalation cohorts (Coh) of TK216 ranging from 18 to 288 mg/m2/day. The MTD for the 14-day infusion was 200 mg/m2/d, which was selected as the recommended phase II dose (RP2D). Treatments were manageable with DLTs of neutropenia/febrile neutropenia, and other AEs of thrombocytopenia, anemia and fatigue. Nine pts have been treated in the expansion Coh with TK216 at the RP2D plus VCR. No new toxicities were noted except neurotoxicity due to VCR. In total, 11 pts were treated with the RP2D, 3 in the final dose escalation Coh and 8 in the expansion Coh, as of May 11, 2020. Observed efficacy was partial response (PR) 18% (2/11), stable disease 45% (5/11), for an overall clinical benefit rate of 64% (7/11). 3 of the patients experienced PD before reaching C2 evaluation (overall PD 36% (4/11). The two clinical responses were notable. One pt had a PR with a regression of all target lung lesions after 2 cycles of TK216 alone. After 6 mos of TK216 +/- VCR therapy, a small residual lesion was removed, for a surgical CR, now continuing for 14+ mos. A second pt had a PR with 90% reduction of target lung lesions by RECIST 1.1 after 2 cycles of TK216 plus VCR.


TK216 was well tolerated and showed encouraging early evidence of anti-tumor activity in a patient population with limited or no treatment options.

Legal entity responsible for the study

Oncternal Therapeutics.


Oncternal Therapeutics.


N. Federman: Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer. R.F. Riedel: Advisory/Consultancy, Research grant/Funding (institution): Oncternal. J. Toretsky: Shareholder/Stockholder/Stock options: Oncternal Therapeutics. X. Ianopulos, F.J. Hsu: Full/Part-time employment: Oncternal Therapeutics. J.B. Breitmeyer: Shareholder/Stockholder/Stock options, Officer/Board of Directors: Oncternal Therapeutics. All other authors have declared no conflicts of interest.