BTX-A51 Treatment Initiated in Advanced Solid Tumor Malignancies


The first patient with an advanced solid tumor has been dosed in a phase 1 clinical trial of the multi-kinase inhibitor BTX-A51.

In a dose-escalation clinical trial of BTX-A51 in patients with advanced solid tumor malignancies dependent on the oncogene MYC the first patient was dosed, according to a press release from BioTheryX, Inc.1

"In the fight against solid tumor cancers, which have extremely poor survival rates and limited treatment options, clinical trials with new therapies are desperately needed," said Zung Thai, MD, PhD, chief medical officer of BioTheryX, in the release. "We are excited to be initiating the dose-escalation portion of this study and progressing to the selection of the phase 2 dose."

BTX-A51 is an oral small molecule multi-kinase inhibitor that blocks specific leukemic stem cell targets like CK1α and super enhancer targets, such as CDK7/CDK9, that prevent the transcription of oncogenic genes like MYC. BTX-A51 activates the tumor suppressor protein p53 and is sustained by the shutdown of MDM2 in combination with transcriptional shutdown of leukemia oncogenes, such as MYC and MCL-1.

By blocking CKIα, CDK7, and CDK9, p53 is stabilized which leads to downregulation of MYC and MCL-1 and promotes killing leukemia cells and leukemic stem cells. Currently, there is a phase 1 dose-escalation clinical trial (NCT04243785) for patients with relapsed/refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS).

Progress for the phase 1 trial looking at the use of BTX-A51 in patients with R/R AML or high-risk MDS was published in Blood as they look to recruit up to 35 patients on BTX-A51.2 The open-label, multi-center, first-in-human study will look at patients at the Memorial Sloan Kettering Cancer Center, MD Anderson Cancer Center, and City of Hope Cancer Center. The maximum tolerated dose (MTD) will be calculated by the isotonic estimate of the toxicity rate that is closest to the target toxicity rate of 0.3. Once that is determined, 15 patients will be enrolled into the dose-expansion phase and will be dosed for 3 weeks on BTX-A51 followed by 1 week off the drug over a 28-day cycle.

Patients eligible for the study must be at least 18 years old with R/R AML or R/R high-risk MDS and ECOG score of 2 with a life expectancy of 6 weeks. Patients excluded for the trial include patients given chemotherapy within 2 weeks prior to the start of BTX-A51, transplantation within 3 months prior to screening, active graft-versus-host diseases that requires systemic immunosuppressive medications, and a white blood cell count > 20 × 109/L. The primary objective of the study is to determine MTD and recommend a phase 2 dose, with secondary objectives of evaluating overall response, survival, and pharmacokinetics.

"This is a significant milestone for BioTheryX, as we look to deliver a much-needed therapeutic option to patients with advanced solid tumor malignancies that are dependent upon MYC," said Robert Williamson, president and chief executive officer of BioTheryX, in the press release. "We are excited for the potential of BTX-A51 to provide a meaningful therapeutic option for patients and are working aggressively to advance our pipeline of molecular glues, PROTACs and monovalent degraders towards the clinic."


  1. BioTheryX Announces First Patient Dosed with BTX-A51 in Phase 1 Clinical Trial in Patients with Advanced Solid Tumors. News release. June 9, 2021. Accessed June 9, 2021.
  2. Ball B., Stein A., Borthakur G., et al. Trial in Progress: A Phase I Trial of BTX-A51 in Patients with Relapsed or Refractory AML or High-Risk MDS. Blood. 2020;136 (suppl 1; 18–19). doi: 10.1182/blood-2020-142557
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