A Study to Investigate APL-4098 Alone and/or in Combination With Azacitidine in R/R AML and High-Risk MDS

Apollo Therapeutics

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Acute Myeloid Leukemia Refractory; Myelodysplastic Syndrome With Excess Blasts; Myelodysplastic Syndrome Acute Myeloid Leukemia; Acute Myeloid Leukemia, in Relapse

Treatments: Drug: Azacitidine and APL-4098; Drug: APL-4098

Study type: Interventional

Funder types: Industry

Identifiers

NCT06372717

AP30CP01

Details and patient eligibility

About

This is an open-label, Phase 1/2 study to determine the safety, tolerability, and efficacy of APL-4098 alone and/or in combination with azacitidine for the treatment of relapsed or refractory (R/R) acute myeloid leukemia (AML), myelodysplastic syndrome (MDS)/AML and MDS-excess blasts (EB). Participants with the MDS-EB subtype will be eligible for the Phase 1 part of the study only.

Enrollment: 112 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 18 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 we 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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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112 participants in 4 patient groups

Dose Escalation Phase: APL-4098 monotherapy

Experimental group

Description:

Dose escalation with different dosing levels of APL-4098.

Treatment:

Drug: APL-4098

Dose Escalation Phase: APL-4098 and azacitidine

Experimental group

Description:

Dose escalation with different dosing levels of APL-4098 in combination with azacitidine (75 mg/m2).

Treatment:

Drug: Azacitidine and APL-4098

Phase 2 Dose Expansion: APL-4098 monotherapy

Experimental group

Treatment:

Drug: APL-4098

Phase 2 Dose Expansion: APL-4098 and azacitidine

Experimental group

Treatment:

Drug: Azacitidine and APL-4098