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

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

Trial statusRecruiting

Trial phasePhase 1

Trial typeInterventional

Biological sexAll

Age18+

SponsorApollo Therapeutics Ltd

About this trial

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).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Design model

Sequential

Treatments tested in this trial

APL-4098
Drug
APL-4098 is administered orally in 28-day cycles
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.
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.

Treatment groups

100 Participants

are divided into 3 treatment groups

Group A: Dose Escalation Phase: APL-4098 monotherapyExperimental treatment 1 intervention

Group B: Dose Escalation Phase: APL-4098 and azacitidineExperimental treatment 1 intervention

Group C: APL-4098 and azacitidine and venetoclaxExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

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

Time frame

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

Time frame

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.

Time frame

Approximately one year

Assess the Pharmacokinetics of APL-4098

Evaluate PK parameters: Maximum plasma concentration (Cmax)

Time frame

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

Secondary outcomes

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

R/R AML and MDS/AML participants: response is assessed per European LeukemiaNet (ELN) 2022 criteria MDS-EB participants: response is assessed per revised International Working Group 2023 response criteria

Time frame

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)