Pivotal Open-label Phase 3 Clinical Study of QTX-2101 in Adult Patients With Acute Promyelocytic Leukemia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Quetzal Therapeutics LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-05-13

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Quetzal Therapeutics

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To characterize the PK of QTX-2101
To characterize the treatment response of QTX2101/ATRA at the end of Consolidation Cycle 3

Secondary objectives 7

1. To characterize the safety and tolerability of QTX-2101 in APL participants
2. To characterize the event-free survival (EFS) of QTX2101/ATRA
3. To characterize additional measures of efficacy of QTX-2101
4. To characterize the safety and tolerability of QTX-2101/ATRA and IV ATO/ATRA
5. To characterize PK profile of QTX-2101
6. To complete a model-based concentration QT relationship evaluation
7. To evaluate the impact of oral versus IV ATO on participant experience, including quality of life, treatment burden, and financial toxicity

Conditions and MedDRA coding

Acute Promyelocytic Leukemia

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

EMA Human Medicines Division

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Participants must be ≥18 to <71 years old at the time of signing an informed consent.
2. Participants must have a diagnosis of APL characterized by the presence of the t(15;17) translocation by fluorescence in situ hybridization or cytogenetics, or PML/RARA gene expression via RT-qPCR.
3. Participants must be classified as low- or intermediate-risk APL, defined as WBC count ≤10×109/L at diagnosis.
4. PART 1 Only: Participants with LR-APL should have completed induction and 3 cycles of Consolidation treatment with IV ATO and ATRA. They should have documented mCR at the time of study entry.
5. PART 2 Only: Participants should be ND LR-APL.
6. Participants must have organ function as defined below: • Serum total bilirubin ≤3.0 mg/dL • Alanine aminotransferase and Aspartate aminotransferase ≤3× upper limit of normal • Creatinine clearance ≥30 mL/min
7. Participants must have an Eastern Cooperative Oncology Group Performance Status of ≤2.
8. Participants must have a serum or high-sensitivity urine pregnancy test (for females of childbearing potential) that is negative at the Screening Visit and immediately prior to initiation of treatment (first dose of study intervention).
9. Participants must be willing and able to comply with the scheduled study visits, treatment plans, including receipt of study intervention at the study site through the end of study period, laboratory tests, contraception guidance, and other procedures. Note: Participants must be willing and able to provide written informed consent and commit to complete the full treatment and follow-up procedures as outlined in the protocol, unless discontinuation is medically indicated or required by the investigator or sponsor.
10. Participants must be capable of giving signed and dated institutional review board or independent ethics committee approved informed consent.

Exclusion criteria 18

1. Participants who have had treatment for APL with ATRA for >7 days prior to the first dose of study intervention (Part 2 only).
2. Participants who have suspected central nervous system involvement with leukemia.
3. Participants with Grade ≥2 neuropathy.
4. Participants with a history of torsade de pointes.
5. Participants with ECG abnormalities, including: • Congenital long QT syndrome. • History or presence of significant ventricular or atrial tachyarrhythmia. • Clinically significant resting bradycardia (<50 beats per minute). • Corrected QT interval (QTc) >450 msec on screening ECG using QTcF, obtained as the mean from 3 QTcF values from a triplicate standard resting ECG at screening. • Right bundle branch block plus left anterior hemiblock, bifascicular block.
6. Participants with unresolved related AEs from prior exposure of IV ATO (Part 1 only) unless the AEs are Grade 1 or completely resolved prior to enrollment.
7. Participants with a current or recent (within 3 months prior to the Screening Visit) history of symptomatic congestive heart failure.
8. Participants who have a known contraindication or hypersensitivity to ATO, ATRA, or any of their excipients, including participants with hypersensitivity to soy and/or peanut (ATRA).
9. Participants who received any other investigational agents within 30 days of the Screening Visit or <5 half-lives since completion of previous investigational therapy, whichever is shorter.
10. Participants with a history of other cancers must not be receiving active treatment (with radiation or chemotherapy) and must be free of disease for 2 years prior to the Screening Visit with the exception of localized prostate cancer treated with hormone monotherapy, breast cancer treated with hormone monotherapy, basal cell carcinoma, nonmelanoma skin cancer, or cervical carcinoma in situ.
11. Participants with an active, life-threatening, or clinically important uncontrolled systemic infection requiring hospitalization.
12. Participants who have a known malabsorption syndrome or other condition that may impair absorption of study medication (eg, gastrectomy) or who are unable to swallow oral medication.
13. Participants who have other severe acute or chronic medical conditions (and/or psychiatric conditions or laboratory abnormalities) that may increase the expected risk to the participant (ie, the risk associated with the study participation or study intervention administration) or that may interfere with the interpretation of study results or, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
14. Immunocompromised participants with increased risk of opportunistic infections, including known human immunodeficiency virus (HIV)-positive participants with CD4 counts ≤350 cells/mm3 or history of opportunistic infection in the last 12 months. To ensure that effective antiretroviral therapy, when used in eligible HIV-positive participants, is tolerated and that toxicities are not confusing with investigational drug toxicities, participants should be on an established antiretroviral therapy for at least 4 weeks and have an HIV viral load less than 400 copies/mL prior to the Screening Visit.
15. Participants who have a known active or chronic hepatitis B or active hepatitis C virus (HCV) infection. Participants with a history of HCV infection who have completed curative therapy for HCV at least 12 weeks before the Screening Visit and have a documented undetectable viral load at the Screening Visit are eligible for randomization.
16. Participants with indications requiring uninterrupted anticoagulation (eg, mechanical heart valves) due to increased risk of hemorrhagic complications during induction (Part 2).
17. Pregnant females, breastfeeding females, and males not willing to comply with contraceptive requirements or females of childbearing potential not willing to comply with contraceptive requirements.
18. Participants who are likely to withdraw consent at the completion of treatment, or during study follow-up, for the sole purpose of enrolling in another interventional clinical study for APL or another investigational therapy, unless recommended by the investigator or sponsor.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. PK parameters, including maximum plasma concentration (Cmax) and area under curve (AUC) for all metabolites of arsenic trioxide, including arsenious acid (AsIII), arsenic acid (ASV), total arsenic, dimethylarsinic acid (DMA), and monomethylarsenic acid (MMA).
2. Molecular complete remission (mCR) defined as absence of promyelocytic leukemia/ retinoic acid receptor alpha (PML/RARA) in the bone marrow per European Leukemia Net (ELN) 2019 criteria for APL. Negativity of PML/RARA is defined as PML/RARA transcript level below 10-4, confirmed by centralized quantitative reverse transcription-polymerase chain reaction (RTqPCR) testing using an assay with a limit of detection (LOD) of 10-5.

Secondary endpoints 7

1. Incidence of adverse events (AEs), clinically significant laboratory changes, significant electrocardiogram (ECG) findings, and vital sign changes.
2. Landmark EFS at the time of the primary endpoint analysis, defined as time from randomization to the date of induction treatment failure (failure to achieve complete remission [CR]/morphologic complete remission [CRi] after induction), no achievement of mCR after 3 consolidation courses, relapse after CR/mCR, or death from any cause, whichever comes first.
3. Other parameters of efficacy, including CR/CRi rate, defined as achieving CR/CRi at the end of induction and end of Consolidation Cycle 3 per ELN 2019 criteria for APL and landmark overall survival (OS), defined as duration from randomization to date of death due to any cause
4. Incidences of AEs, clinically significant laboratory changes, significant ECG, and vital sign changes
5. Summary statistics of QTX-2101 steady-state AUC and Cmax, determined by population PK analysis.
6. Triplicate ECGs with time-matched PK sampling analysis.
7. Participant-reported outcomes assessing quality of life (eg, EORTC QLQ-C30), treatment convenience and satisfaction (eg, CCSQ), health utility (eg, EQ-5D-5L), and overall treatment burden (eg, number of infusion visits, catheter use, and time in treatment)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Quetzal Therapeutics LLC

Sponsor organisation

Quetzal Therapeutics LLC

Address

1 North Wacker Drive Suite 1650

City

Chicago

Postcode

60606-2807

Country

United States

Scientific contact point

Organisation

Quetzal Therapeutics LLC

Contact name

Shaad Abedin, MD FACP

Public contact point

Organisation

Quetzal Therapeutics LLC

Contact name

Shaad Abedin, MD FACP

Third parties 10

Locations

6 EU/EEA countries · 26 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 135 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications