A Phase 2 Study of MAX-40279 Combined With Venetoclax and Azacitidine in Unfit Newly Diagnosed Acute Myeloid Leukemia

This is a prospective, multicenter, phase Ⅱ study consisting of dose escalation and ex-pansion stages in unfit newly diagnosed AML.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: MAX-40279; Drug: Azacitidine; Drug: Venetoclax

Detailed Description

This is a prospective, multicenter, phase Ⅱ study consisting of dose escalation and ex-pansion stages in unfit newly diagnosed AML. Patients in dose escalation stage received oral MAX-40279 at three doses, in combination with VEN and AZA in 28-day cycles. Three to six patients were enrolled at each dose level. The dose limiting toxicities (DLTs) observation period was 28 days after the first dose. All evaluable patients with ≥1 cycle treatment were included in preliminary efficacy analysis.

• Study Type: Interventional
• Enrollment (Estimated): 43
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jing Wang; Phone Number: 8621-61009600; Email: jwang@maxinovel.com

Study Locations

• China
  • Tianjin, China
    • Recruiting
    • Institute of Institute of Hematology & Blood Diseases Hospital ( Chinese Academy of Medical Sciences)
    • Contact: jianxiang Wang, MD; Phone Number: 86-22-23909278; Email: wangjx@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients meeting the World Health Organization (WHO) 2016 diagnostic criteria for newly diagnosed acute myeloid leukemia (AML) patients unfit for intensive chemotherapy:

1. Age ≥65 years, or
2. Age >18 years and ineligible for standard-dose chemotherapy, defined by ≥1 of the following:

ECOG performance status 2 or 3；History of chronic heart failure (CHF) requiring treatment or left ventricular ejection fraction (LVEF) ≤50% DLCO ≤65% or FEV1 ≤65%Creatinine clearance ≥30 mL/min but ≤45 mL/min (Cockcroft-Gault)、Any other condition deemed incompatible with standard chemotherapy (requires PI approval) 2. No prior AML therapy, except:Hydroxyurea. 3. ECOG performance status ≤3 4. Laboratory requirements: WBC≤3×10*9/L、AST/ALT/ALP ≤3×ULN (except: due to leukemic involvement)、Total bilirubin ≤1.5×ULN、Serum creatinine clearance ≥30 mL/min (measured or calculated) 5. Life expectancy ≥3 months 6. Contraception requirements: Negative pregnancy test for women of childbearing potential；Agreement to use effective contraception during treatment and for 6 months after therapy

Exclusion Criteria:

1. AML with BCR::ABL1 fusion、Acute promyelocytic leukemia (APL).
2. Secondary AML, including:Therapy-related AML (per WHO classification)、AML with prior history of myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN).
3. Use of strong/moderate CYP3A4 inducers within 3 days prior to treatment initiation.
4. Hypersensitivity to any study drugs.
5. Active malignancy in other organs (requiring treatment).
6. Active cardiac disease, defined as ≥1 of the following:Myocardial infarction within 6 months before enrollment；History of symptomatic arrhythmia requiring medication；Uncontrolled/symptomatic congestive heart failure (NYHA Class >2)
7. Active infections, including:Untreated tuberculosis or any aspergillosis.
8. Known HIV, active hepatitis B (HBV), or hepatitis C (HCV).
9. Central nervous system (CNS) leukemia at baseline.
10. Conditions limiting oral drug absorption (e.g., malabsorption syndrome).
11. Medical history of:Epilepsy requiring medication、Dementia or psychiatric disorders impairing protocol compliance.
12. Investigator's discretion for ineligibility.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: MAX-40279 Combined with Venetoclax and Azacitidine in unfit newly diagnosed AML; Patients in dose escalation stage received oral MAX-40279 at 40 mg, 50 mg, and 60 mg twice daily (BID), in combination with VEN (100 mg on day 1, 200 mg on day 2, and 400 mg daily thereafter) and AZA (75 mg/m2 days 1-7) in 28-day cycles. Patients in dose expansion stage received RP2D MAX-40279 plus VEN (100 mg on day 1, 200 mg on day 2, and 400 mg daily thereafter) and AZA (75 mg/m2 days 1-7).

Drug: MAX-40279; Dose escalation：MAX-40279: 40 mg, 50 mg, and 60 mg twice daily (BID). Dose expantion: MAX-40279 RP2D. Venetoclax: 100 mg on day 1, 200 mg on day 2, and 400 mg daily thereafter. Azacitidine: 75 mg/m2 days 1-7. 28 days are one cycle.; Drug: Azacitidine; Given by IV, 75 mg/m2; Other Names: Vidaza; Drug: Venetoclax; 100 mg on day 1, 200 mg on day 2, and 400 mg daily thereafter.; Other Names: VENCLEXTA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DLT	The dose limiting toxicities, Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0	Dose escalation; an average of 6 months.
Adverse events (AEs), serious adverse events (SAEs)	Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0	Through study completion; an average of 24 months.
Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D)	Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0	Dose escalation; an average of 6 months.
CRc	complete remission rate	Through study completion; an average of 24 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RFS	Recurrence-Free Survival	Through study completion; an average of 8 months.
DoR	duration of response	Through study completion; an average of 8 months.
OS	overall survival	Through study completion; an average of 24 months.

Collaborators and Investigators

• Sponsor: Maxinovel Pty., Ltd.
• Investigators: Principal Investigator: Jianxiang Wang, MD, Institute of Institute of Hematology & Blood Diseases Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: July 29, 2026
• First Submitted That Met QC Criteria: July 29, 2026
• First Posted (Actual): August 3, 2026

Study Record Updates

• Last Update Posted (Actual): August 3, 2026
• Last Update Submitted That Met QC Criteria: July 29, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Unfit AML
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Azacitidine; venetoclax
• Other Study ID Numbers: MAX-40279-010; CTR20250827 (Registry Identifier: CENTER FOR DRUG EVALUATION, NMPA)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No