Tamibarotene Plus Azacitidine in Participants With Newly Diagnosed RARA-positive Higher-Risk Myelodysplastic Syndrome

Study Overview
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Brief Summary
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This study compares the efficacy of Tamibarotene in combination with azacitidine to azacitidine in combination with placebo in participants who are Retinoic Acid Receptor Alpha (RARA) positive, and newly diagnosed with higher-risk myelodysplastic syndrome (HR-MDS), and who have not received treatment for this diagnosis. The primary goal of the study is to compare the complete remission rate between the two treatment arms.

Detailed Description
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A subset of participants have MDS characterized by an overexpression of the RARA gene. A blood test will be used to identify participants with RARA-positive MDS. Assessment of the RARA biomarker for study eligibility will be done by collection of blood samples from potential study participants at the pre-screening visit and testing at a central laboratory. Participants who meet eligibility requirements will be randomized 2:1 to receive either Tamibarotene plus azacitidine or placebo plus azacitidine.

Official Title
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A Randomized, Double-blind, Placebo-controlled Phase 3 Study of Tamibarotene Plus Azacitidine Versus Placebo Plus Azacitidine in Newly Diagnosed, Adult Patients Selected for RARA-positive Higher-risk Myelodysplastic Syndrome (SELECT MDS-1)

Conditions
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Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: Tamibarotene
* Drug: Placebo
* Drug: Azacitidine


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Participants must be RARA-positive based on the investigational assay. Participants must be newly diagnosed with HR-MDS as follows: Diagnosis of MDS according to the World Health Organization (WHO) classification and classified by the Revised International Prognostic Scoring System (IPSS R) risk category as very high, high, or intermediate risk. Participants must have Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤2. Key Exclusion Criteria: Participants are suitable for and agree to undergo allogeneic hematopoietic stem cell transplant (HSCT) at the time of screening. Participants who need treatment prior to stem cell transplant can receive treatment on this study and stop the study treatment when they are ready to proceed to transplant. Participants who received prior treatment for MDS with any hypomethylating agent, lenalidomide, chemotherapy or allogeneic HSCT.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tamibarotene + Azacitidine<br>Tamibarotene: 6 mg administered orally twice per day (BID) on Days 8 through 28 of each 28-day treatment cycle. Azacitidine: 75 mg/m^2 administered intravenously or subcutaneously each day on Days 1 through 7 of each 28-day treatment cycle. | Drug: Tamibarotene<br>* Administered as specified in the treatment arm<br>* Other names: SY-1425;Drug: Azacitidine<br>* Administered as specified in the treatment arm<br>|
| Placebo Comparator: Tamibarotene Matched Placebo + Azacitidine<br>Placebo: Tamibarotene-matching tablets administered orally BID on Days 8 through 28 of each 28-day treatment cycle. Azacitidine: 75 mg/m^2 administered intravenously or subcutaneously each day on Days 1 through 7 of each 28-day treatment cycle. | Drug: Placebo<br>* Administered as specified in the treatment arm<br>Drug: Azacitidine<br>* Administered as specified in the treatment arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants with Complete Remission |  | Up to 5 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Overall Survival |  | Up to 5 Years | 
| Proportion of Participants Who Achieve Transfusion Independence |  | Up to 5 Years | 
| Proportion of Participants Who Achieve Objective Response |  | Up to 5 Years | 
| Duration of Complete Response |  | Up to 5 Years | 
| Duration of Overall Response |  | Up to 5 Years | 
| Time to Complete Remission |  | Up to 5 Years | 
| Time to Initial Response |  | Up to 5 Years | 
| Duration of Event Free Survival |  | Up to 5 Years | 
| Change in Health-Related Quality of Life (HRQOL) as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 Scale (EORTC QLQ-30) |  | Up to 5 Years | 
| Change in HRQOL as assessed by the European Quality of Life 5 dimensions Scale (EuroQoL-5D) |  | Up to 5 Years | 
| Proportion of participants with Adverse Events and Serious Adverse Events |  | Up to 5 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Higher-Risk, Retinoic Acid Receptor Alpha (RARA) positive, Newly Diagnosed, Myelodysplastic Syndromes