A Study to Investigate APL-4098 Alone and in Combination in Adults With AML or MDS

NCT06372717 | Recruiting Phase 1

• 1 other identifier: AP30CP01
• Study Type: interventional
• Target: 100
• Locations: 2 countries
• Sites: 7

Brief Summary

This is an open-label, Phase 1 study to determine the safety, tolerability, and efficacy of APL-4098 alone, and in combination with azacitidine, and in combination with azacitidine plus venetoclax for the treatment of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS)/AML and MDS-excess blasts (EB).

Conditions

Myelodysplastic Syndrome Acute Myeloid Leukemia; Acute Myeloid Leukemia Refractory; Myelodysplastic Syndrome With Excess Blasts; Acute Myeloid Leukemia, in Relapse; Acute Myeloid Leukemia (AML)

Outcome Measures

Primary Outcomes (6)

• Incidence of Treatment Emergent Adverse Events [Safety]

  Evaluation of safety parameters including treatment emergent adverse events as detected by hematology, chemistry, coagulation safety labs, physical exams, vital signs, Electrocardiogram results

  Through study completion, approximately one year

• Incidence of Dose Limiting Toxicities [Tolerability]

  Evaluation of tolerability parameters including dose limiting toxicities as detected by hematology, chemistry, coagulation safety labs, physical exams, vital signs, and Electrocardiogram results

  Cycle 1 Day 1 to Cycle 2 Day 1 (a cycle is 28 days)

• Determine Recommended Phase 2 Dose (RP2D)/Recommended dose range (RDR) levels of APL-4098 alone, in combination with azacitidine, and in combination with azacitidine plus venetoclax.

  Approximately one year

• Assess the Pharmacokinetics of APL-4098

  Evaluate PK parameters: Maximum plasma concentration (Cmax)

  On Days 1, 2, 8, and 15 of Cycle 1, and on Day 1 of Cycle 2 (each cycle is 28 days)

• Assess the Pharmacokinetics of APL-4098

  Evaluate PK parameters: area under the curve (AUC)

  On Days 1, 2, 8, and 15 of Cycle 1, and on Day 1 of Cycle 2 (each cycle is 28 days)

• Assess the Pharmacokinetics of APL-4098

  Evaluate PK parameters: Time to peak concentration (Tmax)

  On Days 1, 2, 8, and 15 of Cycle 1, and on Day 1 of Cycle 2 (each cycle is 28 days)

Secondary Outcomes (1)

• Assess response to disease with APL-4098 alone, in combination with azacitidine, and in combination with azacitidine plus venetoclax.

  Response is assessed at Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 7 Day 1 (each cycle is 28 days long), then every three cycles thereafter (assessed for up to 2 years)

Study Arms (3)

Dose Escalation Phase: APL-4098 monotherapy

EXPERIMENTAL

Dose escalation with different dosing levels of APL-4098.

Drug: APL-4098

Dose Escalation Phase: APL-4098 and azacitidine

EXPERIMENTAL

Dose escalation with different dosing levels of APL-4098 in combination with azacitidine.

Drug: Azacitidine and APL-4098

APL-4098 and azacitidine and venetoclax

EXPERIMENTAL

Dose escalation with different dosing levels of APL-4098 in combination with azacitidine and venetoclax.

Drug: Azacitidine and Venetoclax and APL-4098

Interventions

Azacitidine and Venetoclax and APL-4098 DRUG

Azacitidine is administered at the standard dose on Day 1 - Day 7 of each 28-day cycle; Venetoclax is administered orally; APL-4098 is administered orally.

APL-4098 and azacitidine and venetoclax

APL-4098 DRUG

APL-4098 is administered orally in 28-day cycles

Dose Escalation Phase: APL-4098 monotherapy

Azacitidine and APL-4098 DRUG

Azacitidine is administered at the standard dose on Day 1 - Day 7 of each 28-day cycle; APL-4098 is administered orally.

Dose Escalation Phase: APL-4098 and azacitidine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years or older
• Confirmed diagnosis of relapsed refractory acute myeloid leukemia (R/R AML), myelodysplastic syndrome (MDS)/ AML, or MDS-excess blasts (MDS-EB) with the following characteristics: - R/R AML (primary or secondary, including treatment-related), participant is intolerant to, or considered ineligible for available therapies known to provide clinical benefit.
• WBC count ≤ 25,000/microliter
• ECOG Performance Status of ≤ 2
• Weight ≥ 40kg
• Female participants of childbearing potential must have negative serum pregnancy test at screening; must not plan to become pregnant or have ova harvested or breastfeed while on study; must be willing to use specific contraception or avoid intercourse
• Male participants must be willing to use specific contraception and not plan to impregnant a female partner or donate sperm while on study
• Participant must be willing and able to provide written informed consent and to comply with the requirements of the trial

You may not qualify if:

• Certain prior therapies such as: received an allogeneic stem cell transplant within 6 months of screening, received an autologous stem cell transplant within 3 months of screening, received any anti-cancer treatments within 2 weeks of Cycle 1 Day 1, prior radiation therapy within 4 weeks of screening
• Certain medical conditions such as: other malignancies, myocardial infarction within 6 months of screening, symptomatic congestive heart failure, uncontrolled active infection, history of arterial thrombosis within 6 months of screening
• Diagnostic assessments: Left ventricular ejection fraction \< 45%, Fridericia's corrected QT interval \> 470msec, Aspartate aminotransferase and/or alanine aminotransferase \> 3 x upper limit of normal (ULN), total bilirubin \> 1.5 x ULN, calculated or measured creatinine clearance \< 45 mL/minute (multiply by 0.85 if female)
• Infectious disease: HIV positive, active hepatitis B and/or C

Sponsors & Collaborators

• Apollo Therapeutics Ltd: lead

Study Sites (7)

Monash Health

Clayton, Victoria, 3168, Australia

RECRUITING

St. Vincent's Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

RECRUITING

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

RECRUITING

Hollywood Private Hospital

Nedlands, Western Australia, 6009, Australia

RECRUITING

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

RECRUITING

The Royal Marsden Hospital

London, SM2 5PT, United Kingdom

RECRUITING

Sarah Cannon Research Institute UK

London, W1G 0PU, United Kingdom

RECRUITING

MeSH Terms

Conditions

GATA2 Deficiency; Anemia, Refractory, with Excess of Blasts; Leukemia, Myeloid, Acute

Interventions

Azacitidine; venetoclax

Condition Hierarchy (Ancestors)

Myelodysplastic Syndromes; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Anemia, Refractory; Anemia; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Sanjay Aggarwal, MD

  Apollo Therapeutics

  STUDY CHAIR

Central Study Contacts

Apollo Therapeutics

CONTACT

781-479-2267; AP30@apollotx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2024
• First Posted: April 18, 2024
• Study Start: June 4, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: February 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2); AU (5)