Testing APG-115 alone or with other drugs in patients with acute myeloid leukemia or myelodysplastic syndromes

A Phase Ib Study to Investigate the Safety, Pharmacokinetics and Pharmacodynamics of APG-115 as a Single Agent or in Combination With Azacitidine or Cytarabine in Patients With Relapse/Refractory AML and Relapsed/Progressed High/Very High Risk MDS

This study is testing a new drug called APG-115 alone and with other medications to see if it can help people with tough cases of acute myeloid leukemia or myelodysplastic syndromes.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 102 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ascentage Pharma Group Inc. (Industry-sponsored)
• Locations: 14 sites (Beijing, Beijing Municipality and 13 other locations)
• Trial ID: NCT04275518 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and pharmacokinetics of APG-115, a small-molecule MDM2 inhibitor, in patients with relapsed or refractory acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS). The study is structured in three stages: the first stage focuses on determining the maximum tolerated dose (MTD) of APG-115 as a single agent, the second stage assesses the combination of APG-115 with azacitidine or cytarabine, and the third stage involves dose expansion of the combination regimens. Patients will receive treatment for up to six cycles or until disease progression or unacceptable toxicity occurs.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with relapsed or refractory AML or high-risk MDS.

Not a fit: Patients with acute promyelocytic leukemia or those who have recently undergone leukemia biotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with difficult-to-treat AML and MDS.

How similar studies have performed: Other studies have shown promising results with MDM2 inhibitors in hematological malignancies, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Patients with a diagnosis of histologically confirmed relapsed or refractory (R/R) acute myeloid leukemia by WHO classification or relapsed/progressed high/very high risk MDS (score≥4.5) according to IPSS-R risk stratification
2. Age \>/= 18 years.
3. Adequate organ function
4. Subject must have a projected life expectancy of at least 12 weeks.
5. ECOG performance status of 0-1.
6. Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient or his legally authorized representative is required prior to their enrollment on the protocol.
7. Subject has a white blood cell count\< 50 × 109/L. Note: Hydroxyurea is permitted to meet this criterion.

Exclusion Criteria:

1. Subject has acute promyelocytic leukemia.
2. Patients must not have had leukemia biotherapy 4 weeks prior to starting investigational drug, or less than 5 half-lives small molecular targeted drug therapy, or 28 days any anti-cancer therapy (whichever is longer)
3. Uncontrolled intercurrent illness including, but not limited to active uncontrolled infection, symptomatic congestive heart failure (NYHA Class III or IV), unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
4. Active infection requiring systemic antibiotic/antifungal medication, known clinically active hepatitis B or C, or HIV infection.
5. Participants who have received allogeneic HSCT, or autologous HSCT within 12 months.
6. Patients with active, uncontrolled CNS leukemia will not be eligible.
7. Any prior systemic MDM2-p53 inhibitor treatment
8. Any other condition or circumstance that would, in the opinion of the investigator, make the patient unsuitable for participation in the study.
9. Subject has a history of other malignancies within 2 years prior to study entry, with the exception of:

   * Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast;
   * Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
   * Previous malignancy confined and surgically resected (or treated with other modalities) with curative intention: requires discussion with sponsor.

Where this trial is running

Beijing, Beijing Municipality and 13 other locations

• The First Hospital of Peking University — Beijing, Beijing Municipality, China (Not_yet_recruiting)
• Guangzhou panyu central hospital — Guangzhou, Guangdong, China (Recruiting)
• Nanfang Hospital of Southern Medical University — Guangzhou, Guangdong, China (Recruiting)
• Henan Provincial Oncology Hospital — Zhengzhou, Henan, China (Recruiting)
• Union Hospital medical college Huazhong University of Science and Technology — Wuhan, Hubei, China (Recruiting)
• Zhongnan Hospital of Wuhan University — Wuhan, Hubei, China (Recruiting)
• Xiangya Hospital Central South University — Changsha, Hunan, China (Recruiting)
• The First Affilated Hospital of Ganzhou Medical University — Suzhou, Jiangsu, China (Not_yet_recruiting)
• The First affiliated hospital of Soochow University — Suzhou, Jiangsu, China (Recruiting)
• The First Affiliated Hospital of Nanchang University — Nanchang, Jiangxi, China (Not_yet_recruiting)
• First Hospital of Jilin University — Changchun, Jilin, China (Recruiting)
• Shanghai Jiao Tong University school of medicine Ruijing Hospital — Shanghai, Shanghai Municipality, China (Recruiting)
• Shanghai Sixth people's Hospital — Shanghai, Shanghai Municipality, China (Recruiting)
• Blood Diseases Hospital Chinese Academy of Medical Sciences — Tianjin, Tianjin Municipality, China (Recruiting)

Study contacts

• Principal investigator: Jianxiang Wang, M.D. — Blood Diseases Hospital Chinese Academy of Medical Sciences
• Study coordinator: Junyuan Qi, M.D.

Conditions Acute Myeloid Leukemia; Myelodysplastic Syndromes; APG-115; AML; MDS