Multi-centre Phase 1/2 study testing LB-208 for adults with relapsed/refractory AML or high-risk MDS

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Aop Orphan Pharmaceuticals GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-04-15

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

AOP Orphan Pharmaceuticals GmbH

External identifiers

EU CT number

2025-523396-38-00

WHO UTN

U1111-1326-3978

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Dose response, Efficacy, Safety, Pharmacokinetic, Pharmacodynamic

- To evaluate the safety, and tolerability of LB-208 administered continuously as a single agent dosed orally in participants with r/r AML and r/r HR-MDS.
- To determine MTD and/or the recommended Phase 2 dose of LB-208 in participants with r/r AML and r/r HR-MDS.

Secondary objectives 2

1. To characterize the pharmacokinetic (PK) profile of LB-208 in participants with r/r AML and r/r HR-MDS.
2. To assess the preliminary efficacy and clinical activity of LB-208 in participants with r/r AML and r/r HR-MDS.

Conditions and MedDRA coding

Relapse or refractory (r/r) acute myeloid leukaemia (AML) and r/r higher-risk (HR) myelodysplastic syndrome (MDS)

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. 1. Written informed consent obtained prior to performing any protocol related procedure.
2. 2. Participants must be able to understand and willing to sign an informed consent.
3. 3. Participants must be male or female ≥18 years of age at the time of signing the informed consent.
4. 4. Participants must have an advanced haematologic malignancy either AML or MDS diagnosed according to the World Health Organization (WHO) 2022 classification and relapse or refractory disease according ELN 2022 or IWG2023 as listed below: - Relapsed AML as defined by ELN 2022 and World Health Organization (WHO) criteria in patients with pathologically documented AML that has failed standard treatment, or patients who received at least one prior line of therapy including intensive chemotherapy, hypomethylating agents, or standard therapies including targeted therapies (unless the therapy is contraindicated or intolerable) with no available therapies known to provide clinical benefit in the opinion of the treating investigator. - Primary refractory AML as defined by ELN 2022 and WHO criteria: patients failing to achieve remission after 2 cycles of induction (including at least 1 cycle of intermediate dose cytarabine) not eligible for intensive chemotherapy (ChT); or - Patients failing to achieve response after two cycles of venetoclax in combination with hypomethylating agents (HMA). - MDS with increased blasts (subtype MDS-IB1 or MDS-IB2) or considered high and very high risk by the IPSS-R (Greenberg et al., 2012), that is recurrent or refractory, or the participant is intolerant to established cytoreductive or targeted therapy known to provide clinical benefit for their condition (i.e., participant must not be candidates for regimens known to provide clinical benefit), according to the treating physician.
5. 5. Participant must be amenable to serial BM biopsies, peripheral blood (PB) sampling, and urine sampling during the study. For diagnosis and response assessment after Cycle 1 (C2D1±7 days) BM trephine biopsy is mandatory. Further response evaluation of AML or HR-MDS can be made by BM aspiration when a core biopsy is unobtainable. A BM biopsy is required in case of dry tap or failure (mainly dilution) with the aspiration.
6. 6. Participants must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (see Appendix 1).
7. 7. Platelet count ≥20,000/µL (Transfusions to achieve this level are allowed.)
8. 8. Participants must have adequate hepatic function as evidenced by aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) ≤3.0 × ULN, unless considered due to leukaemic disease.
9. 9. Participants must have adequate renal function as evidenced by: - Serum creatinine ≤2.0 mg/dL × ULN, or - Creatinine clearance >40 mL/min based on the Cockroft-Gault glomerular filtration rate (GFR) estimation (see Appendix 2): (140 - Age) x (weight in kg) x (0.85 if female)/72 x serum creatinine.
10. 10. Life expectancy ≥ 3 months.
11. 11. Female participants with reproductive potential must have a negative serum pregnancy test within 7 days prior to the start of therapy. Participants with reproductive potential are defined as one who is biologically capable of becoming pregnant.
12. 12. Women of childbearing potential as well as fertile men and their partners must agree to abstain from sexual intercourse or to use a highly effective form of contraception during the study and for 90 days (males) and 6 months (females) following the last dose of LB-208 (see Appendix 3). In addition, males must not donate sperm during dosing and 3 months after stopping study treatment.

Exclusion criteria 19

1. 1. Participants who have undergone a HSCT within 60 days of the first dose of LB-208, or participants on immunosuppressive therapy post HSCT at the time of screening, or with clinically significant graft-versus-host disease (GVHD). (The use of topical steroids for ongoing skin GVHD is permitted.)
2. 2. Participants who received systemic anticancer therapy (with exception of hydroxyurea) or radiotherapy <14 days prior to their first day of study drug administration.
3. 3. Participants who received an investigational agent <14 days prior to their first day of study drug administration. In addition, the first dose of LB-208 should not occur before a period ≥5 half-lives of the investigational agent have elapsed.
4. 4. Patients for whom potentially curative anticancer therapy is available.
5. 5. Patients taking sensitive CYP 2B6 and CYP 2C8 substrate medications as defined by FDA drug-drug interaction (DDI) Website: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers (see Appendix 4).
6. 6. Patients who are pregnant or breast feeding.
7. 7. Patients with an active severe infection or with an unexplained fever >38.5°C during screening visits or on their first day of study drug administration (at the discretion of the Investigator, participant with tumour fever may be enrolled).
8. 8. Participants with known hypersensitivity to any of the components of LB-208.
9. 9. Participants with New York Heart Association (NYHA) Class III or IV congestive heart failure or LVEF <40%.
10. 10. Participants with a history of myocardial infarction within the last 6 months.
11. 11. Participants with known unstable or uncontrolled angina pectoris.
12. 12. Participants with a known history of severe and/or uncontrolled ventricular arrhythmias.
13. 13. Participants with heart-rate corrected QT (QTc) interval ≥470 msec or with other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalaemia, family history of long QT interval syndrome).
14. 14. Participants taking medications that are known to prolong the QT interval unless such treatment can be permanently discontinued or substituted before first dosing (recommended washout ≥5 half-lives or per SmPC). - For the purpose of this protocol, drugs with a known risk of QT prolongation are defined according to the CredibleMeds® database (www.crediblemeds.org) or the information provided in the current Summary of Product Characteristics (SmPC). - Medications classified as possible or conditional risk may be permitted following case-by-case evaluation by the Investigator in consultation with the Medical Monitor.
15. 15. Participants with infection with human immunodeficiency virus (HIV), active hepatitis B or C or any other active systemic infection (Grade ≥2).
16. 16. Participants with any other medical or psychological condition, deemed by the Investigator to be likely to interfere with a subject’s ability to sign informed consent, cooperate, or participate in the study.
17. 17. Participants with known dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally.
18. 18. Participants with clinical symptoms suggesting active central nervous system (CNS) leukaemia or known CNS leukaemia. Evaluation of cerebrospinal fluid is only required if there is a clinical suspicion of CNS involvement by leukaemia during screening.
19. 19. Participants with immediately life-threatening, severe complications of leukaemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Safety, and toxicity will be described by observed frequency and severity graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0., including dose limiting toxicity (DLT) rate, adverse events (AEs), serious adverse events (SAEs), and AEs leading to discontinuation.

Secondary endpoints 2

1. Plasma concentration-time profiles, and PK parameters of LB-208.
2. Response according to the revised European LeukemiaNet (ELN) Response Criteria in AML (Döhner et al., 2022) and revised International Working Group 2023 (IWG 2023) in HR-MDS (Zeidan, Platzbecker, et al., 2023). Response for all patients will be assessed by the site Investigators.

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Aop Orphan Pharmaceuticals GmbH

Sponsor organisation

Aop Orphan Pharmaceuticals GmbH

Address

Leopold-Ungar-Platz 2, Doebling Doebling

City

Vienna

Postcode

1190

Country

Austria

Scientific contact point

Organisation

Aop Orphan Pharmaceuticals GmbH

Contact name

Dr. Martin Unger

Public contact point

Organisation

Aop Orphan Pharmaceuticals GmbH

Contact name

Dr. Martin Unger

Third parties 9

Locations

1 EU/EEA country · 6 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 16 files

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

Application history

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