A Phase Ib Study of APG-115 Single Agent or in Combination With Azacitidine or Cytarabine in Patients With AML and MDS.
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
Ascentage Pharma Group Inc.
102 participants
Jul 6, 2020
INTERVENTIONAL
Conditions
Summary
Acute myeloid leukemia is a malignant disorder characterized by the rapid, uncontrolled proliferation of malignant clonal hematopoietic stem cells that accumulate as immature, undifferentiated cells (blasts) in the bone marrow and circulation. APG-115 is a potent and orally active small-molecule MDM2 inhibitor, it binds to MDM2 protein and shows potent cell growth inhibitory activity in vitro with low nanomolar potencies in a subset of human cancer cell lines. APG-115 has demonstrated its strong antitumor activities with either daily or less frequent dosing-schedules in the acute leukemia xenograft models. This is a phase 1b, open-label, three-stages study that will initially evaluate the safety and PK/PD profile of APG-115 as a single agent, followed by a combination of APG-115 + azacytidine or cytarabine in R/R AML or MDS subjects. Patients will continue treatment for maximally 6 cycles or until progression of disease or unacceptable toxicity is observed or administrative discontinuation whichever occurs first. Patients who continue to be benefit after 6 cycles' treatment will receive additional cycles of treatment until progression of disease, unacceptable toxicity is observed or administrative discontinuation. (As long as it is proven safe).
Eligibility
Inclusion Criteria7
- 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
- Age \>/= 18 years.
- Adequate organ function
- Subject must have a projected life expectancy of at least 12 weeks.
- ECOG performance status of 0-1.
- 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.
- Subject has a white blood cell count\< 50 × 109/L. Note: Hydroxyurea is permitted to meet this criterion.
Exclusion Criteria12
- Subject has acute promyelocytic leukemia.
- 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)
- 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.
- Active infection requiring systemic antibiotic/antifungal medication, known clinically active hepatitis B or C, or HIV infection.
- Participants who have received allogeneic HSCT, or autologous HSCT within 12 months.
- Patients with active, uncontrolled CNS leukemia will not be eligible.
- Any prior systemic MDM2-p53 inhibitor treatment
- Any other condition or circumstance that would, in the opinion of the investigator, make the patient unsuitable for participation in the study.
- 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.
Interventions
APG-115 orally once daily from Days 1 to 7 every 28 days.
75 mg/m\^2 SC QD on Days 1- 7 (28-day cycle)
1g/m\^2 IV QD on Days 3-7 (28-day cycle)
Locations(14)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT04275518