New Arsenic Trioxide Agent Earns FDA Fast Track Designation in AML Subtype

The FDA has granted fast track designation to QTX-2101, an investigational arsenic trioxide therapy, as a treatment for patients with acute promyelocytic leukemia (APL), according to a press release from the developer, Quetzal Therapeutic.¹

APL, a rare and aggressive acute myeloid leukemia (AML) subtype appearing in approximately 10% to 15% of AML cases, is marked by the PML-RARA gene fusion. This condition may also confer severe bleeding complications and rapidly progressing disease if left untreated. Current standards of care in APL necessitate several lengthy infusions over the course of therapy, which may significantly burden patients and their support networks.

Developers designed QTX-2101 as an oral capsule formulation of arsenic trioxide to mitigate current limitations related to intravenous therapy, including reoccurring clinic visits. Investigators are currently assessing the ability of QTX-2101 to simplify treatment administration and sustain precise dosing in APL.

Evaluation of QTX-2101 is underway in an international, multicenter phase 3 trial, which is comparing the oral capsule with standard-of-care treatment among patients with newly diagnosed APL. Developers announced the launch of this phase 3 trial in December 2025.²

“The launch of this phase 3 trial is an important milestone in the development of QTX-2101,” Shaad Abedin, MD, chief medical officer at Quetzal Therapeutics, stated in a press release regarding the trial’s launch.² “While survival rates in APL are favorable, treatment-related burden and tolerability remain significant challenges. Our oral capsule formulation is designed to address key limitations of intravenous arsenic trioxide, with the goal of making treatment more accessible and manageable for patients and providers.”

The phase 3 trial will evaluate the safety, efficacy, and pharmacokinetics of QTX-2101 among those with APL. This assessment may build upon pharmacokinetic and safety data reported in previous phase 1 studies assessing oral arsenic trioxide in this patient population.

According to findings from a phase 1 trial (NCT04996030) published in Blood Advances, oral arsenic trioxide demonstrated similar pharmacokinetics compared with intravenous arsenic trioxide.³ Additionally, 3 patients (23%) who received arsenic trioxide intravenously experienced an adverse effect (AE) compared with 4 (33%) who received the oral formulation. One patient who received oral arsenic trioxide had treatment-related vomiting, while another had serious AEs involving bacteremia and sepsis that were not associated with study therapy.

“The [pharmacokinetic] and safety data generated from this study support further development of [QTX-2101] in APL. Given the nearly identical [pharmacokinetic] exposures by area under the curve [AUC] of [QTX-2101] and [intravenous arsenic trioxide], future study evaluating the use of [QTX-2101] to treat patients with APL may allow the opportunity to demonstrate clinical benefit using bioequivalence and more expeditiously advance the development of this long-awaited oral [arsenic trioxide] formulation,” lead study author Farhad Ravandi-Kashani, MD, from the Department of Leukemia at The University of Texas MD Anderson Cancer Center, wrote with coauthors in the study publication.³

Investigators of the phase 1 study characterized the pharmacokinetics, safety, and tolerability of oral and intravenous arsenic trioxide based on 2 distinct modules: a single-dose pharmacokinetic module, and a multiple-dose oral module. Primary end points included the maximum observed plasma concentration and AUC of oral arsenic trioxide across both modules.⁴ AEs represented a secondary end point.

Patients 18 years and older with APL characterized by the presence of the t(15;17) translocation or PML/RARA gene expression, prior induction therapy with arsenic trioxide plus all-trans-retinoic acid (ATRA), and eligibility to receive consolidation therapy with arsenic trioxide plus ATRA were permitted to enroll on the trial. Being in morphological complete remission at the end of induction therapy was another requirement for study entry.

References

1. QTX-2101 awarded FDA fast track designation for the treatment of acute promyelocytic leukemia. News release. Quetzal Therapeutics. January 29, 2026. Accessed January 29, 2026. https://tinyurl.com/37cc5axz
2. Quetzal Therapeutics launches phase III clinical trial of oral QTX-2101 for acute promyelocytic leukemia (APL). News release. Quetzal Therapeutics. December 2, 2025. Accessed January 29, 2026. https://tinyurl.com/33azj54r
3. Ravandi F, Rangaraju S, Kantarjian H, et al. A pharmacokinetic and safety study of oral arsenic trioxide in patients with acute promyelocytic leukemia. Blood Adv. 2025;9(9):2136-2143. doi:10.1182/bloodadvances.2024015453
4. A study for oral SY-2101 for participants with acute promyelocytic leukemia. ClinicalTrials.gov. January 23, 2024. Accessed January 29, 2026. https://tinyurl.com/499zjw2z