The following article features coverage from the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

When combined with vincristine, the ETS inhibitor TK216 demonstrated antitumor activity in patients with relapsed/refractory Ewing sarcoma, according to results from a phase 1/2 trial.

The trial ( Identifier: NCT02657005) was presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting by Ravin Ratan, MD, of The University of Texas MD Anderson Cancer Center in Houston.

Dr Ratan explained that TK216 targets ETS proteins that fuse with the EWS gene, preventing protein-protein interactions and downregulating the aberrant transcription factors that drive Ewing sarcoma. TK216 is the first agent to target the ETS family of oncoproteins.

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Dr Ratan reported results for 68 patients treated with TK216 in the phase 1/2 study. There were 33 patients in phase 1 who were treated at different doses and schedules.

Phase 2 included 35 patients treated with the recommended phase 2 dose (RP2D) of TK216 plus vincristine. The RP2D of TK216 was 200 mg/m2 per day, given via continuous IV infusion for 14 days.

At baseline, the patients’ mean age was 27 years, 63.2% of patients were men, and the median number of prior systemic treatments was 3. The majority of patients had prior surgery (77.9%) and radiation (83.8%). Metastases were present in 98.5% of patients at study entry, with the most common sites being lung and/or bone.

All 68 patients were evaluable for safety. The most common adverse events were anemia (50%), neutropenia (47.1%), and fatigue (41.2%).

“Myelosuppression is the primary safety observation, which is transient, reversible, and responsive to growth factors,” Dr Ratan said.

There were 54 patients who were evaluable for efficacy overall and 31 evaluable patients who had received the RP2D of TK216 plus vincristine.

The overall response rate was 5.6%, and the complete response rate was 3.7%. All 3 responses — 2 complete responses and 1 partial response — occurred in patients who received the RP2D of TK216 plus vincristine.

The disease control rate was 29.6% in all evaluable patients and 45.2% in patients who received the RP2D. The median duration of stable disease was 1.8 months and 1.9 months, respectively.

“Preliminary efficacy is encouraging, with 2 complete and durable responses,” Dr Ratan said.

At a median-follow-up of 4.6 months, the median progression-free survival in patients treated with the RP2D and vincristine was 1.9 months, which translated to a 6-month PFS rate of 15.5%.

The phase 2 portion of the study is ongoing and open for enrollment.

Disclosures: This research was supported by Oncternal Therapeutics. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Read more of Cancer Therapy Advisor’s coverage of the 2021 ASCO Annual Meeting by visiting the conference page.


Ludwig JA, Federman NC, Anderson PM, et al. TK216 for relapsed/refractory Ewing sarcoma: Interim phase 1/2 results. J Clin Oncol. 2021;39:(suppl 15; abstr 11500). doi:10.1200/JCO.2021.39.15_suppl.11500