Syros Trials
The SYROS SELECT trials are investigating tamibarotene, a selective oral RARα agonist, in certain patients with
HR-MDS and AML
We are currently investigating the selective oral RARα agonist tamibarotene in patients with newly-diagnosed HR-MDS and AML who are positive for RARA gene overexpression. With tamibarotene, we seek to deliver a targeted approach that can lead to durable clinical responses in HR-MDS and AML patients who are positive for RARA overexpression.
Many patients with HR-MDS and AML are positive for RARA overexpression, as determined by an investigational blood test for RARA overexpression1,2
of patients with HR-MDS
of patients with AML
Consider referring potentially eligible patients for further evaluation and possible participation in the trials.
Upon referral, an investigational blood test will be used to identify patients who are positive for RARA overexpression.
Tamibarotene is an investigational agent and is not approved for use in any indication in the U.S. or Europe.
TRIAL INQUIRIESAML, acute myeloid leukemia; HR-MDS, higher-risk myelodysplastic syndrome; RARα, retinoic acid receptor alpha.
References: 1. RARA-positivity based on Syros data on file from Study SY-1425-201 and the SELECT-MDS-1 Study (27May2022) from over 175 patients with MDS. 2. Clinical Study SY-1425-201 Protocol. Syros Pharmaceuticals, Inc.
Trial overview
The SELECT-MDS-1 trial is a global phase 3 clinical trial for patients with newly diagnosed higher-risk myelodysplastic syndrome (HR-MDS) identified as positive for RARA overexpression.
PHASE / Phase 3
PATIENT / Newly diagnosed HR-MDS and positive for RARA overexpression
STUDY DRUGS / Tamibarotene in combination with azacitidine
STATUS / Recruiting
The SELECT-AML-1 trial is a global phase 2 clinical trial for patients with newly diagnosed unfit acute myeloid leukemia (AML) identified as positive for RARA overexpression.
PHASE / Phase 2
PATIENT / Newly diagnosed unfit AML and positive for RARA overexpression
STUDY DRUGS / Tamibarotene in combination with venetoclax and azacitidine
STATUS / Recruiting
Tamibarotene is an investigational agent and is not approved for use in any indications in the U.S. or Europe.
Trial details
Tamibarotene plus azacitidine in patients with newly diagnosed higher-risk myelodysplastic syndrome who are positive for RARA overexpression.
STUDY POPULATION / Patients with newly diagnosed HR-MDS who are positive for RARA overexpression
STUDY TREATMENT / Patients randomized 2:1 to receive either tamibarotene + azacitidine or placebo + azacitidine
KEY STUDY CRITERIA /
Inclusion*:
- Age ≥18 years old
- RARA-positive, as determined by an investigational blood test for RARA overexpression
- Newly diagnosed with HR-MDS per WHO classification and very high, high, or intermediate risk per IPSS-R classification
- Measurable disease with bone marrow blast count >5%
- ECOG performance status of ≤2
Exclusion*:
- Suitable for and agree to undergo allogeneic HSCT at the time of screening
- Received prior treatment for MDS with any hypomethylating agent, chemotherapy, or allogeneic HSCT
PRIMARY ENDPOINT / CR rate
KEY SECONDARY ENDPOINT / OS
SECONDARY ENDPOINTS / ORR, EFS, TI, DOCR, DOR, TTCR, TTR, AEs/SAEs, and change in HRQOL
Tamibarotene is an investigational agent and is not approved for use in any indication in the U.S. or Europe.
ClinicalTrials.gov Identifier: NCT04797780
*Additional criteria apply.
AE, adverse event; CR, complete remission; DOCR, duration of complete response; DOR, duration of overall response; ECOG, Eastern Cooperative Oncology Group; EFS, event-free survival; HR-MDS, higher-risk myelodysplastic syndrome; HRQOL, health-related quality of life; HSCT, hematopoietic stem cell transplantation; IPSS-R, Revised International Prognostic Scoring System; ORR, overall response rate; OS, overall survival; RARα, retinoic acid receptor alpha; SAE, serious adverse event; TI, transfusion independence; TTCR, time to complete remission; TTR, time to response; WHO, World Health Organization.
Tamibarotene plus venetoclax/azacitidine in patients with newly diagnosed AML
STUDY POPULATION / Patients with newly diagnosed unfit AML who are positive for RARA overexpression
STUDY TREATMENT / Patients randomized 1:1 to receive either tamibarotene + venetoclax/azacitidine or venetoclax/azacitidine
KEY STUDY CRITERIA /
Inclusion*:
- RARA-positive, as determined by an investigational blood test for RARA overexpression
- Must have newly diagnosed, previously untreated non-acute promyelocytic leukemia (APL) AML with a bone marrow or peripheral blood blast count ≥20% and be unlikely to tolerate standard intensive chemotherapy at the time of study entry due to age, performance status, or comorbidities based on at least one of the following criteria:
- Age ≥75 years old
- Age <75 years old, with ≥1 of the following:
- ECOG performance status of 3
- cardiac history of CHF or documented EF ≤50%
- pulmonary disease with DLCO ≤65% or FEV1 ≤65%
- creatinine clearance ≥30 mL/min to <45 mL/min per Cockcroft-Gault estimation
- hepatic impairment with total bilirubin >1.5 to ≤3.0 ULN
- any other comorbidity that the investigator judges to be incompatible with intensive chemotherapy
Exclusion*:
- Has APL
- Has known active central nervous system involvement with AML
- Prior treatment for the diagnosis of AML, MDS, or antecedent hematologic malignancy with any hypomethylating agent, venetoclax, chemotherapy, or HSCT, with the exception of prior treatment with hydroxyurea
PRIMARY ENDPOINT / CR/CRi rate
SECONDARY ENDPOINTS / AEs, CR, CR/CRh, DOCR, DOCR/CRi, DOCR/CRh, TTCR, TTCR/CRi, TTCR/CRh, ORR, plasma concentration of tamibarotene
Tamibarotene is an investigational agent and is not approved for use in any indication in the U.S. or Europe.
ClinicalTrials.gov Identifier: NCT04905407
*Additional criteria apply.
AE, adverse event; AML, acute myeloid leukemia; APL, acute promyelocytic leukemia; CHF, congestive heart failure; CR, complete remission; CRh, complete remission with partial hematologic recovery; CRi, complete remission with incomplete count recovery; DOCR, duration of complete remission; DLCO, diffusing capacity of the lungs for carbon monoxide; ECOG, Eastern Cooperative Oncology Group; HSCT, hematopoietic stem cell transplantation; ORR, overall response rate; RARα, retinoic acid receptor alpha; TTCR, time to complete remission; ULN, upper limit of normal.
