A Study to Evaluate the Safety and Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of Max-40279-01 in Combination With Azacitidine (AZA) in Patients With Myelodysplastic Syndrome (MDS) or Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)

Study Overview
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Brief Summary
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This study is a phase Ib/II study of Max-40279-01 in combination with Azacitidine (AZA) in patients with Myelodysplastic Syndrome (MDS) or Relapsed/Refractory Acute Myeloid Leukemia (R/R AML). This study include Phase Ib and Phase II study. The phase Ib study is designed to evaluate the safety and tolerability of MAX-40279-01 in combination with Azacitidine (AZA) in patients with Relapsed or Refractory AML. The phase II study is designed to preliminarily assess the efficacy and safety of Max-40279-01 in combination with Azacitidine (AZA) in patients with Myelodysplastic Syndrome (MDS) or Relapsed/Refractory Acute Myeloid Leukemia (R/R AML).

Detailed Description
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This is a two-part study comprised of a dose escalation part and a dose expansion part.

Official Title
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A Single-arm, Multi-Center, Phase Ib/Ⅱ Clinical Trial of Max-40279-01 in Combination With Azacitidine (AZA) in Adult Patients With Myelodysplastic Syndrome (MDS) or Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)

Conditions
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Leukemia, Acute Myeloid Leukemia, Relapsed/Refractory Acute Myeloid Leukemia, Myelodysplastic Syndrome

Intervention / Treatment
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* Drug: MAX-40279-01


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and/or females over age 18 A diagnosis of AML according to the World Health Organization (WHO) 2016 criteria with relapsed or refractory disease and have exhausted, or are ineligible for therapeutic options, or int-risk or high-risk or very high-risk MDS according to revised International Prognostic Scoring System (IPSS-R); Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Expected survival >3 months. No radiotherapy, surgery or hormonal therapy for any kind of within 2 weeks prior to participating in this study. Patients must have fully recovered from the acute toxicities of any prior treatment with any anti-cancer drugs (including hypomethylating agents in MDS patients), radiotherapy or other anti-cancer modalities (i.e., returned to baseline status as noted before most recent treatment) for any tumors. Patients with persisting, stable chronic toxicities from such prior treatment ≤Grade 1 are eligible, but must be documented as such. Signed informed consent form. Exclusion Criteria: Acute promyelocytic leukemia according to World Health Organization 2016 criteria Known central nervous system involvement Medical history of difficulty swallowing, malabsorption or other chronic gastrointestinal disease, or conditions that may hamper compliance and/or absorption of the tested product Known allergies, hypersensitivity, or intolerance to Max-40279-01 or AZA or the excipients of these treatments Previously treated malignancies other than the current disease, except for adequately treated non-melanoma skin cancer, in situ cancer, or other cancer from which the subject has been disease-free for at least 5 years at the trial entry

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Max-40279-01 in combination with Azacitidine (AZA)<br>This is an open-label Phase Ib/II clinical study. The study will be conducted in two parts: Part I: Phase Ib dose escalation. Participants receive Max-40279-01 in combination with azacytidine (AZA), with different dose schedules. Part II: Phase II dose expansion. Participants divide into positive group and negative group according to whether FLT3 gene mutation occurs, approximately 40 people per group. All participants receive the recommended dose for Part 2 of Max-40279-01 with azacytidine (AZA). | Drug: MAX-40279-01<br>* Drug: AZA AZA will be administered at 75 mg/m^2 by subcutaneous injection for 7 consecutive days from D1 to D7 in 28-day treatment cycles. Other Name: Azacitidine Drug: Max-40279-01 Max-40279-01 will be administered as a combination of multiple oral capsules containing 5 and 25 mg. An alternate combination of 35 mg, 50 mg and 60 mg Max-40279-01 twice a day may be utilized. Other Name: NA<br>* Other names: Azacitidine (AZA);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) | To explore the maximum tolerable dose (MTD) of Max-40279-01 in combination with Azacitidine (AZA) for patients with r/r AML or MDS, the recommended phase II dose (RP2D). | Through study Part 1 completion, an average of 6 months | 
| Phase II dose (RP2D) | Recommended phase II dose (RP2D) | Through study Part 1 completion, an average of 6 months | 
| Overall survival(OS) |  | Up to 24 months | 
| Rate of complete remission (CRc) | including Complete Remission with incomplete Platelet recovery (CRp) and Complete Remission with incomplete hematologic recovery (CRi) | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax | Time to maximum plasma concentration | Approximately 4 weeks | 
| Cmax | Maximum plasma drug concentration | Approximately 4 weeks | 
| AUC | Area under the time-concentration curve | Approximately 4 weeks | 
| t1/2 | Observed terminal half-life | Approximately 4 weeks | 
| Objective response rate (ORR) | The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on IRWG. | 1 months (anticipated) | 
| Safety and tolerability assessed by incidence and severity of adverse events | All grade ≥ 3 toxicities according to CTCAE (Common Terminology Criteria for Adverse Events) version 5 will be tabulated | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapsed/Refractory Acute Myeloid Leukemia, Myelodysplastic Syndrome