A Phase Ib Study of APG-115 Single Agent or in Combination With Azacitidine or Cytarabine in Patients With AML and MDS.
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorAscentage Pharma Group Inc.
About this trial
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 criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
APG-115
DrugAPG-115 orally once daily from Days 1 to 7 every 28 days.
Azacitidine
Drug75 mg/m\^2 SC QD on Days 1- 7 (28-day cycle)
Cytarabine
Drug1g/m\^2 IV QD on Days 3-7 (28-day cycle)
Treatment groups
102 Participants
are divided into 2 treatment groupsGroup A: APG-115/APG-115+Cytarabine in Relapse/Refractory AMLExperimental treatment 2 interventions
Group B: APG-115/APG-115+Aza in relapsed/progressed high risk MDSExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Dose Limiting Toxicities (DLT)
DLT will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE, version 5) by organ system. DLT will be defined as clinically significant drug-related adverse events during the Cycle one.
Time frame
From day 1 to the end of cycle 1 (each cycle is 28 days).Secondary outcomes
1
Overall Response Rate (ORR)
ORR is defined by CR + CRi+ PR (according to IWG AML（2003）and IWG MDS（2006）criteria)
Time frame
Evaluated for response by the end of cycle 1 and cycle 2, and then 2 months thereafter till complete 6 cycles treatment or 1 month after last dose (each cycle is 28 days).2
Overall survival (OS)
From date of treatment start until the date of death due to any cause or date of termination of the study, whichever came first. Termination of the Study: The last subject has completed at least 6 cycle's treatment or the subject discontinues treatment for any reason.
Time frame
Measured up to 6 months after the last subject has received treatment.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
Source ClinicalTrials.gov