Phase 3 Study of Oral Arsenic Trioxide QTX-2101 in Newly Diagnosed Low-Risk Acute Promyelocytic Leukemia

The primary objective is to characterize the pharmacokinetic profile of QTX-2101 and to assess treatment response with QTX-2101 in combination with all-trans retinoic acid at the end of Consolidation Cycle 3. This is clinically relevant for defining systemic exposure and for determining disease response in acute promyelocytic leukemia. The secondary objectives are to characterize safety and tolerability of QTX-2101 in participants with acute promyelocytic leukemia, to characterize event-free survival with QTX-2101/all-trans retinoic acid, to characterize additional efficacy measures, to characterize safety and tolerability of QTX-2101/all-trans retinoic acid and intravenous arsenic trioxide/all-trans retinoic acid, to complete a model-based concentration-QT relationship evaluation, and to evaluate the impact of oral versus intravenous arsenic trioxide on participant experience, including quality of life, treatment burden, and financial toxicity.

The trial included 72 participants with acute promyelocytic leukemia. The study population included both females and males and consisted of patients aged 18 to less than 71 years. Participants were selected on the basis of a confirmed diagnosis of low- or intermediate-risk disease, defined by a white blood cell count of ≤10×10⁹/L at diagnosis, and required adequate organ function and an Eastern Cooperative Oncology Group Performance Status of ≤2. In Part 1, participants had completed induction and three cycles of consolidation treatment and had documented molecular complete remission at study entry. In Part 2, participants were newly diagnosed with low-risk disease. Additional requirements included the ability to provide informed consent and to comply with scheduled visits, treatment plans, laboratory testing, contraception guidance, and follow-up procedures. No information was provided regarding diet, physical activity, or other lifestyle considerations.

This is an open-label, phase 3, controlled clinical study in newly diagnosed, low-risk acute promyelocytic leukemia. The trial evaluates QTX-2101 in combination with all-trans retinoic acid and includes a comparator regimen with intravenous arsenic trioxide. The main objectives are to characterize the pharmacokinetics of QTX-2101 and to assess treatment response at the end of Consolidation Cycle 3. The overall trial duration is planned from 2026-02-23 to 2032-03-03. Study participation begins with a screening visit to confirm eligibility, including disease characteristics, risk classification, organ function, performance status, and pregnancy testing where applicable. After enrollment and treatment initiation, participants undergo scheduled follow-up visits for study intervention administration, laboratory assessments, ECGs, vital signs, pharmacokinetic sampling, and efficacy evaluations. An end-of-study visit is performed at study completion to collect final safety and outcome data. Expected participant involvement extends through the full treatment and follow-up period outlined in the protocol. Early termination may occur if discontinuation is medically indicated or required by the investigator or sponsor, or if the participant is unable to comply with the scheduled study visits, treatment plan, or other required procedures.

QTX-2101 was administered as a hard capsule containing arsenic trioxide, with a dose of 15 mg by oral use. It was used in combination with all-trans retinoic acid in the study. The trial objective included characterization of the pharmacokinetics of QTX-2101 and assessment of treatment response for the QTX-2101/ATRA regimen at the end of Consolidation Cycle 3.

Arsenic trioxide comparator treatment was provided as Arsenic trioxide Accord 1 mg/ml concentrate for solution for infusion. It was administered by intravenous administration at a dose of 0.15 mg/kg. The study was open-label and phase 3.

Acute promyelocytic leukemia efficacy will be assessed by molecular complete remission (mCR), defined as absence of PML/RARA in the bone marrow per European Leukemia Net 2019 criteria. Negativity of PML/RARA is defined as a transcript level below 10-4, confirmed by centralized quantitative reverse transcription-polymerase chain reaction testing using an assay with a limit of detection of 10-5. Treatment response will also be evaluated at the end of Consolidation Cycle 3. Other efficacy parameters include complete remission/complete remission with incomplete hematologic recovery rate at the end of induction and at the end of Consolidation Cycle 3, landmark event-free survival, and landmark overall survival.

Pharmacokinetic assessment will include maximum plasma concentration and area under the curve for arsenic trioxide metabolites, including arsenious acid, arsenic acid, total arsenic, dimethylarsinic acid, and monomethylarsenic acid. Summary statistics of steady-state area under the curve and maximum plasma concentration will be determined by population PK analysis. Triplicate ECGs with time-matched PK sampling analysis are also planned. Participant-reported outcomes will assess quality of life, treatment convenience and satisfaction, health utility, and overall treatment burden.