Study of Lisaftoclax (APG-2575) Single Agent and Combination With Therapy in Patients Relapsed/Refractory AML

Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorAscentage Pharma Group Inc.

About this trial

The purpose of this study is to assess the safety, pharmacokinetic profile of Lisaftoclax (APG-2575) single agent and in combination with HHT/AZA in patients with relapsed/refractory AML and related myeloid malignancies.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

In accordance with the World Health Organization (WHO) 2016 diagnostic criteria for relapsed or refractory acute myeloid leukemia (AML), Mixed phenotype acute leukemia(MPAL), Chronic myelomonocytic leukemia (CMML), Higher-risk myelodysplastic syndrome (HR-MDS) , Blastic plasmacytoid dendritic cell neoplasm (BPDCN) and naïve AML ineligible for treatment with a standard chemotherapy due to age or comorbidities.

Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0 -2 (0 to 3 for participants >= 60 to 74 years of age who are evaluated as ineligible for treatment with standard chemotherapy).

Subjects can accept oral administration of Lisaftoclax (APG-2575).

Life expectancy ≥ 3 months.

Disqualifiers

Patients diagnosed with acute promyelocytic leukemia or t(9;22)(q34.1;q11.2); BCR-ABL1 positive AML patients.

The persistent toxicities caused by previous chemotherapy or radiotherapy has not been restored to lower than grade 2 by CTCAE 5.0 (except for alopecia).

Known leukemia infiltration of the central nervous system.

Symptomatic active fungal, bacterial and/or viral infections.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Lisaftoclax (APG-2575)

    Drug

    Lisaftoclax (APG-2575) orally once daily, every 28 days as a cycle.

  • Reduced-dose HHT

    Drug

    1mg IV QD on Days 1-14 (28-day cycle).

  • standard-dose HHT

    Drug

    2mg/m\^2 IV QD on Days 1-7 (28-day cycle).

  • Azacitidine

    Drug

    75 mg/m\^2 SC or Iv gtt QD on Days 1- 7 (28-day cycle).

  • Lisaftoclax (APG-2575)

    Drug

    Lisaftoclax (APG-2575) orally once daily for 14 days, every 28 days as a cycle.

  • olverembatinib

    Drug

    orally, with meals, QOD, every 28 days as a cycle.

Treatment groups

682 Participants
are divided into 8 treatment groups

8

Treatment groups

See each treatment group below.

Group A: Lisaftoclax (APG-2575) single agentExperimental treatment 1 intervention
Group B: Lisaftoclax (APG-2575)+reduced-dose HHTExperimental treatment 2 interventions
Group C: Lisaftoclax (APG-2575)+ standard-dose HHTExperimental treatment 2 interventions
Group D: Lisaftoclax (APG-2575)+ AZAExperimental treatment 2 interventions
Group E: Lisaftoclax (APG-2575)+ AZA(HR-MDS.)Experimental treatment 2 interventions
Group F: Lisaftoclax (APG-2575)+ AZA(Naïve AML.)Experimental treatment 2 interventions
Group G: Lisaftoclax (APG-2575)+AZA+OlverembatinibExperimental treatment 3 interventions
Group H: Lisaftoclax (APG-2575)+HHT+OlverembatinibExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

Dose Limiting Toxicities (DLT)

DLT will be graded according to NCI CTCAE Version 5.0. DLT will be defined as clinically significant drug-related adverse events during cycle one.

Time frame
28 days
2

Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose(RP2D)

MTD/RP2D will be determined based on DLTs observed during cycle one.

Time frame
28 days

Secondary outcomes

1

Maximum plasma concentration (Cmax)

Cmax of Lisaftoclax (APG-2575) will be assessed in the patients in single agent or combo study.

Time frame
28 days
2

Area under the plasma concentration versus time curve (AUC)

AUC of Lisaftoclax (APG-2575) will be assessed in the patients in single agent or combo study.

Time frame
28 days
3

Objective Response Rate (ORR)

ORR is defined by CR+ CRi + PR(according to IWG AML(2003)).Response will be evaluated on cycle 1 and every even cycles till completing 6 cycles treatment or end of treatment.

Time frame
Up to 6 cycles (each cycle is 28 days).
4

progression free survival (PFS)

From date of treatment start until the date of progression or the date of death due to any cause.

Time frame
Up to 2 years.

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Ascentage Pharma Group Inc.

Lead sponsor

Suzhou Yasheng Pharmaceutical Co., Ltd.

Collaborator