A Phase 2 interventional study of Tamibarotene and Venetoclax in Acute Myeloid Leukemia, sponsored by Syros Pharmaceuticals. Terminated at 28 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-02-24.
Sponsored by Syros Pharmaceuticals · Phase 2, Interventional, and Treatment
Tamibarotene is being studied as a treatment for participants with a type of leukemia called acute myeloid leukemia, or AML for short. Tamibarotene is being studied as a treatment for participants with AML whose cancer has a specific genetic abnormality characterized by the overexpression of the retinoic acid receptor alpha (RARA) gene. This genetic profile is found in about 3 of every 10 people with AML.
During the trial, tamibarotene will be given with 2 other drugs that are already used together to treat people who have AML and who cannot start treatment with standard chemotherapy.
This study consists of 3 parts. In Part 1, the safety, tolerability, and pharmacokinetic (PK) evaluation of tamibarotene/venetoclax/azacitidine combination will inform the appropriate tamibarotene dose to be combined with the standard of care (SOC) venetoclax/azacitidine in Part 2 and Part 3. In Part 2, participants will be randomized 1:1 to receive either tamibarotene/venetoclax/azacitidine or venetoclax/azacitidine to compare the clinical activity of the 2 combinations. In Part 3, tamibarotene will be added to the venetoclax/azacytidine regimen of a subset of Part 2 participants who experience progressive disease, relapse after initial complete remission (CR) or CR with incomplete blood count recovery (CRi) response, or treatment failure.
3,035 studies on the registry are indexed under Leukemia, Myeloid, Acute; 746 are open to participants now.
This study's enrollment of 66 is above the median of 40 across 2,561 interventional studies indexed under Leukemia, Myeloid, Acute.
Browse Leukemia, Myeloid, Acute studies →Syros Pharmaceuticals is the lead sponsor of 6 studies on the registry; none are open to participants now.
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Note: all inclusion/exclusion criteria should be met prior to the first dose of venetoclax/azacitidine on Cycle 1 Day 1 with the exception of the RARA-biomarker test result referenced in inclusion criterion 2, which should be positive by Cycle 1 Day 8 to continue treatment on study.
Inclusion Criteria:
Participants must have newly diagnosed, previously untreated non-acute promyelocytic leukemia (APL) AML with a bone marrow or peripheral blood blast count ≥20% and must be unlikely to tolerate standard intensive chemotherapy at the time of Cycle 1 Day 1 Visit due to age, performance status, or comorbidities based on at least one of the following criteria:
age \<75 years old, with at least one of the following:
Exclusion Criteria:
Participants will receive the tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 milligrams (mg)/square meter (m\^2) once daily, on Days 1 through 7 of each 28-day therapy cycle (per VIDAZA USPI). Alternative dosing of azacitidine (Days 1 through 5, 8, and 9) will be permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing is 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg twice daily (BID) orally, on Days 8 through 28 of each 28-day therapy cycle. Tamibarotene will only be administered to participants who have been confirmed as RARA-positive.
Drug: Tamibarotene · Drug: Venetoclax · Drug: Azacitidine
Participants will receive the tamibarotene/venetoclax/azacitidine triplet combination at the dose and regimen selected in Part 1.
Drug: Tamibarotene · Drug: Venetoclax · Drug: Azacitidine
Participants will receive the venetoclax/azacitidine combination at the dose and regimen selected in Part 1.
Drug: Venetoclax · Drug: Azacitidine
Part 2 participants treated with venetoclax/azacitidine who experience progressive disease, relapse after initial CR or CRi response, or treatment failure may begin subsequent treatment in Part 3, where tamibarotene will be added to their regimen.
Drug: Tamibarotene · Drug: Venetoclax · Drug: Azacitidine
Tamibarotene tablets will be administered per dose and schedule specified in the arm.
Venetoclax tablets will be administered per dose and schedule specified in the arm.
Also known as: Venclexta
Azacitidine injection will be administered per dose and schedule specified in the arm.
Also known as: Vidaza
Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any untoward medical occurrence that developed or worsened in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. A TEAE was any untoward medical occurrence associated with use of a study drug/study participation, whether or not considered related to study drug after first dose. TEAEs were defined as those adverse events AEs with onset after the first dose of study treatment or existing events that worsened after the first dose during the study up until the last dose of study treatment plus 30 days. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'.
Time frame: Up to 3 years
Part 2: Complete Remission/Complete Remission With Incomplete Hematologic Recovery (CR/CRi) Rate
CR/CRi rate was estimated by the percentage of participants who achieved complete Remission (CR) and/or CR with incomplete hematologic recovery (CRi),CR/CRi (as determined by the investigator). CR was defined as absolute neutrophil count ≥1,000/µL, platelets count ≥100,000/µL, bone marrow blasts \<5% and absence of circulating blasts and blasts with auer rods; absence of extramedullary disease.CRi was defined as absolute neutrophil count \<1,000/µL, platelets count \<100,000/µL, bone marrow blasts \<5% and all CR criteria met except either neutrophils or platelets not recovered.
Time frame: Up to 3 years
Part 1: Overall Response Rate (ORR)
ORR: percentage of participants who achieved a overall response as comprised of CR(ANC ≥1,000/µL, platelets count (PC) ≥100,000/µL, bone marrow blasts \<5% and absence of circulating blasts and blasts with auer rods;absence of extramedullary disease),CRi (ANC \<1,000/µL, PC \<100,000/µL, bone marrow blasts \<5% and all CR criteria met except either neutrophils or platelets not recovered), CRh (ANC \>500/µL, PC \>500,000/µL, bone marrow blasts \<5% and all CR criteria met except ANC and platelets with partial recovery of peripheral counts), morphologically leukemia-free state (bone marrow blasts \<5%, absence of blasts with auer rods and \<5% blasts in marrow sample with a count of at least 200 nucleated cells or cellularity ≥10%. Absence of EMD. No hematologic criteria required.), or PR was defined as ANC \<1,000/µL, PC \<100,000/µL, ≥50% decrease from baseline, with decrease to 5-25. ORR was calculated as ORR (%)=number of overall responders/number of participants in the Safety Population×100.
Time frame: Up to 3 years
Part 1: Plasma Concentration of Tamibarotene
Time frame: Day 8 and 22 of Cycle 1, Day 15 of Cycles 2 and 3 (cycle length = 28 days)
Part 2: Number of Participants With Treatment Emergent Adverse Events
An AE was defined as any untoward medical occurrence that developed or worsened in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. A TEAE was any untoward medical occurrence associated with use of a study drug/study participation, whether or not considered related to study drug after first dose. TEAEs were defined as those adverse events AEs with onset after the first dose of study treatment or existing events that worsened after the first dose during the study up until the last dose of study treatment plus 30 days. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'.
Time frame: Up to 3 years
Part 2: Complete Remission (CR) Rate
CR rate was estimated by the percentage of participants who achieved complete remission (as determined by the investigator). CR was defined as absolute neutrophil count ≥1,000/µL, platelets count ≥100,000/µL, bone marrow blasts \<5% and absence of circulating blasts and blasts with auer rods; absence of extramedullary disease.
Time frame: Up to 3 years
Part 2: Complete Remission/ Complete Remission With Partial Hematologic Recovery (CR/CRh) Rate
CR/CRh rate was estimated by the percentage of participants who achieved complete Remission (CR) and/or CR with partial hematologic recovery (CRh),CR/CRh (as determined by the investigator). CR was defined as absolute neutrophil count ≥1,000/µL, platelets count ≥100,000/µL, bone marrow blasts \<5% and absence of circulating blasts and blasts with auer rods; absence of extramedullary disease.CRh was defined as absolute neutrophil count \>500/µL, platelets count \>500,000/µL, bone marrow blasts \<5% and all CR criteria met except ANC and platelets with partial recovery of peripheral counts.
Time frame: Up to 3 years
Part 2: Duration of Complete Remission
Duration of CR was defined as duration from the date of first documented evidence of CR to the date of relapse of disease (as determined by the investigator), or death due to any cause, whichever occurred first. CR was defined as absolute neutrophil count ≥1,000/µL, platelets count ≥100,000/µL, bone marrow blasts \<5% and absence of circulating blasts and blasts with auer rods; absence of extramedullary disease.
Time frame: Up to 3 years
Part 2: Duration of CR/CRi
Duration of CR/CRi was defined as duration from the date of first documented evidence of CR/CRi to the date of relapse of disease (as determined by the investigator), or death due to any cause, whichever occured first.CR was defined as absolute neutrophil count ≥1,000/µL, platelets count ≥100,000/µL, bone marrow blasts \<5% and absence of circulating blasts and blasts with auer rods; absence of extramedullary disease.CRi was defined as absolute neutrophil count \<1,000/µL, platelets count \<100,000/µL, bone marrow blasts \<5% and all CR criteria met except either neutrophils or platelets not recovered.
Time frame: Up to 3 years
Part 2: Duration of CR/CRh
Duration of CR/CRh was defined as duration from the date of first documented evidence of CR/CRh to the date of relapse of disease (as determined by the investigator), or death due to any cause, whichever occured first. CR was defined as absolute neutrophil count ≥1,000/µL, platelets count ≥100,000/µL, bone marrow blasts \<5% and absence of circulating blasts and blasts with auer rods; absence of extramedullary disease. CRh was defined as absolute neutrophil count \>500/µL, platelets count \>500,000/µL, bone marrow blasts \<5% and all CR criteria met except ANC and platelets with partial recovery of peripheral counts.
Time frame: Up to 3 years
Part 2: Time to Complete Response
Time to CR was defined as the duration from the date of Cycle 1 Day 1 visit to the date of the first documented evidence of CR as determined by the investigator. CR was defined as absolute neutrophil count ≥1,000/µL, platelets count ≥100,000/µL, bone marrow blasts \<5% and absence of circulating blasts and blasts with auer rods; absence of extramedullary disease.
Time frame: Up to 3 years
Part 2: Time to CR/CRi
Time to CR/CRi was defined as the duration from the date of Cycle 1 Day 1 Visit to the date of the first documented evidence of CR/CRi as determined by the investigator. CR was defined as absolute neutrophil count ≥1,000/µL, platelets count ≥100,000/µL, bone marrow blasts \<5% and absence of circulating blasts and blasts with auer rods; absence of extramedullary disease.CRi was defined as absolute neutrophil count \<1,000/µL, platelets count \<100,000/µL, bone marrow blasts \<5% and all CR criteria met except either neutrophils or platelets not recovered.
Time frame: Up to 3 years
Part 2: Time to CR/CRh
Time to CR/CRh was defined as the duration from the date of Cycle 1 Day 1 Visit to the date of the first documented evidence of CR/CRh as determined by the investigator. CR was defined as absolute neutrophil count ≥1,000/µL, platelets count ≥100,000/µL, bone marrow blasts \<5% and absence of circulating blasts and blasts with auer rods; absence of extramedullary disease. CRh was defined as absolute neutrophil count \>500/µL, platelets count \>500,000/µL, bone marrow blasts \<5% and all CR criteria met except ANC and platelets with partial recovery of peripheral counts.
Time frame: Up to 3 years
Part 2: Overall Response Rate
ORR: percentage of participants who achieved a overall response as comprised of CR(ANC ≥1,000/µL, platelets count (PC) ≥100,000/µL, bone marrow blasts \<5% and absence of circulating blasts and blasts with auer rods;absence of extramedullary disease),CRi (ANC \<1,000/µL, PC \<100,000/µL, bone marrow blasts \<5% and all CR criteria met except either neutrophils or platelets not recovered), CRh (ANC \>500/µL, PC \>500,000/µL, bone marrow blasts \<5% and all CR criteria met except ANC and platelets with partial recovery of peripheral counts), morphologically leukemia-free state (bone marrow blasts \<5%, absence of blasts with auer rods and \<5% blasts in marrow sample with a count of at least 200 nucleated cells or cellularity ≥10%. Absence of EMD. No hematologic criteria required.), or PR was defined as ANC \<1,000/µL, PC \<100,000/µL, ≥50% decrease from baseline, with decrease to 5-25. ORR was calculated as ORR (%)=number of overall responders/number of participants in the Safety Population×100.
Time frame: Up to 3 years
| Milestone | Part 1: Tamibarotene/Venetoclax/Azacitidine | Part 2: Tamibarotene/Venetoclax/Azacitidine | Part 2: Venetoclax/Azacitidine | Part 3: Tamibarotene/Venetoclax/Azacitidine |
|---|---|---|---|---|
| Started | 10 | 25 | 26 | 0 |
| Received at least 1 dose of study drug | 10 | 25 | 26 | 0 |
| Intent to treat analysis set | 0 | 25 | 26 | 0 |
| Safety analysis set | 10 | 24 | 27 | 0 |
| Modified intent-to-treat (mitt) analysis set | 0 | 25 | 26 | 0 |
| Response evaluable population | 9 | 0 | 0 | 0 |
| Completed | 1 | 17 | 17 | 0 |
| Not completed | 9 | 8 | 9 | 0 |
| Withdrew: Withdrawal by subject | 2 | 1 | 1 | 0 |
| Withdrew: Death | 7 | 7 | 7 | 0 |
| Withdrew: Other than specified | 0 | 0 | 1 | 0 |
| Milestone | Part 1: Tamibarotene/Venetoclax/Azacitidine | Part 2: Tamibarotene/Venetoclax/Azacitidine | Part 2: Venetoclax/Azacitidine | Part 3: Tamibarotene/Venetoclax/Azacitidine |
|---|---|---|---|---|
| Started | 0 | 0 | 0 | 5 |
| Received at least 1 dose of study drug | 0 | 0 | 0 | 5 |
| Safety analysis set | 0 | 0 | 0 | 5 |
| Completed | 0 | 0 | 0 | 3 |
| Not completed | 0 | 0 | 0 | 2 |
| Withdrew: Death | 0 | 0 | 0 | 2 |
An adverse event (AE) was defined as any untoward medical occurrence that developed or worsened in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. A TEAE was any untoward medical occurrence associated with use of a study drug/study participation, whether or not considered related to study drug after first dose. TEAEs were defined as those adverse events AEs with onset after the first dose of study treatment or existing events that worsened after the first dose during the study up until the last dose of study treatment plus 30 days. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'.
| Participants | Part 1: Tamibarotene/Venetoclax/Azacitidine |
|---|---|
| Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 10 |
CR/CRi rate was estimated by the percentage of participants who achieved complete Remission (CR) and/or CR with incomplete hematologic recovery (CRi),CR/CRi (as determined by the investigator). CR was defined as absolute neutrophil count ≥1,000/µL, platelets count ≥100,000/µL, bone marrow blasts \<5% and absence of circulating blasts and blasts with auer rods; absence of extramedullary disease.CRi was defined as absolute neutrophil count \<1,000/µL, platelets count \<100,000/µL, bone marrow blasts \<5% and all CR criteria met except either neutrophils or platelets not recovered.
| Percentage of participants | Part 2: Tamibarotene/Venetoclax/Azacitidine | Part 2: Venetoclax/Azacitidine |
|---|---|---|
| Part 2: Complete Remission/Complete Remission With Incomplete Hematologic Recovery (CR/CRi) Rate | 60.00 (38.7 to 78.9) | 69.23 (48.2 to 85.7) |
ORR: percentage of participants who achieved a overall response as comprised of CR(ANC ≥1,000/µL, platelets count (PC) ≥100,000/µL, bone marrow blasts \<5% and absence of circulating blasts and blasts with auer rods;absence of extramedullary disease),CRi (ANC \<1,000/µL, PC \<100,000/µL, bone marrow blasts \<5% and all CR criteria met except either neutrophils or platelets not recovered), CRh (ANC \>500/µL, PC \>500,000/µL, bone marrow blasts \<5% and all CR criteria met except ANC and platelets with partial recovery of peripheral counts), morphologically leukemia-free state (bone marrow blasts \<5%, absence of blasts with auer rods and \<5% blasts in marrow sample with a count of at least 200 nucleated cells or cellularity ≥10%. Absence of EMD. No hematologic criteria required.), or PR was defined as ANC \<1,000/µL, PC \<100,000/µL, ≥50% decrease from baseline, with decrease to 5-25. ORR was calculated as ORR (%)=number of overall responders/number of participants in the Safety Population×100.
| Percentage of participants | Part 1: Tamibarotene/Venetoclax/Azacitidine |
|---|---|
| Part 1: Overall Response Rate (ORR) | 77.78 (40.0 to 97.2) |
No measurements were reported for this outcome.
An AE was defined as any untoward medical occurrence that developed or worsened in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. A TEAE was any untoward medical occurrence associated with use of a study drug/study participation, whether or not considered related to study drug after first dose. TEAEs were defined as those adverse events AEs with onset after the first dose of study treatment or existing events that worsened after the first dose during the study up until the last dose of study treatment plus 30 days. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'.
| Participants | Part 2: Tamibarotene/Venetoclax/Azacitidine | Part 2: Venetoclax/Azacitidine |
|---|---|---|
| Part 2: Number of Participants With Treatment Emergent Adverse Events | 24 | 24 |
CR rate was estimated by the percentage of participants who achieved complete remission (as determined by the investigator). CR was defined as absolute neutrophil count ≥1,000/µL, platelets count ≥100,000/µL, bone marrow blasts \<5% and absence of circulating blasts and blasts with auer rods; absence of extramedullary disease.
| Percentage of participants | Part 2: Tamibarotene/Venetoclax/Azacitidine | Part 2: Venetoclax/Azacitidine |
|---|---|---|
| Part 2: Complete Remission (CR) Rate | 48.00 (27.8 to 68.7) | 57.69 (36.9 to 76.6) |
CR/CRh rate was estimated by the percentage of participants who achieved complete Remission (CR) and/or CR with partial hematologic recovery (CRh),CR/CRh (as determined by the investigator). CR was defined as absolute neutrophil count ≥1,000/µL, platelets count ≥100,000/µL, bone marrow blasts \<5% and absence of circulating blasts and blasts with auer rods; absence of extramedullary disease.CRh was defined as absolute neutrophil count \>500/µL, platelets count \>500,000/µL, bone marrow blasts \<5% and all CR criteria met except ANC and platelets with partial recovery of peripheral counts.
| Percentage of participants | Part 2: Tamibarotene/Venetoclax/Azacitidine | Part 2: Venetoclax/Azacitidine |
|---|---|---|
| Part 2: Complete Remission/ Complete Remission With Partial Hematologic Recovery (CR/CRh) Rate | 48.00 (32.2 to 75.6) | 57.69 (42.7 to 83.6) |
Duration of CR was defined as duration from the date of first documented evidence of CR to the date of relapse of disease (as determined by the investigator), or death due to any cause, whichever occurred first. CR was defined as absolute neutrophil count ≥1,000/µL, platelets count ≥100,000/µL, bone marrow blasts \<5% and absence of circulating blasts and blasts with auer rods; absence of extramedullary disease.
| days | Part 2: Tamibarotene/Venetoclax/Azacitidine | Part 2: Venetoclax/Azacitidine |
|---|---|---|
| Part 2: Duration of Complete Remission | 293.0 (66.0 to NA) | 256.5 (56.0 to NA) |
Duration of CR/CRi was defined as duration from the date of first documented evidence of CR/CRi to the date of relapse of disease (as determined by the investigator), or death due to any cause, whichever occured first.CR was defined as absolute neutrophil count ≥1,000/µL, platelets count ≥100,000/µL, bone marrow blasts \<5% and absence of circulating blasts and blasts with auer rods; absence of extramedullary disease.CRi was defined as absolute neutrophil count \<1,000/µL, platelets count \<100,000/µL, bone marrow blasts \<5% and all CR criteria met except either neutrophils or platelets not recovered.
| days | Part 2: Tamibarotene/Venetoclax/Azacitidine | Part 2: Venetoclax/Azacitidine |
|---|---|---|
| Part 2: Duration of CR/CRi | 293.0 (66.0 to NA) | 253.0 (56.0 to 263.0) |
Duration of CR/CRh was defined as duration from the date of first documented evidence of CR/CRh to the date of relapse of disease (as determined by the investigator), or death due to any cause, whichever occured first. CR was defined as absolute neutrophil count ≥1,000/µL, platelets count ≥100,000/µL, bone marrow blasts \<5% and absence of circulating blasts and blasts with auer rods; absence of extramedullary disease. CRh was defined as absolute neutrophil count \>500/µL, platelets count \>500,000/µL, bone marrow blasts \<5% and all CR criteria met except ANC and platelets with partial recovery of peripheral counts.
| days | Part 2: Tamibarotene/Venetoclax/Azacitidine | Part 2: Venetoclax/Azacitidine |
|---|---|---|
| Part 2: Duration of CR/CRh | 293.0 (66.0 to NA) | 256.5 (56.0 to NA) |
Time to CR was defined as the duration from the date of Cycle 1 Day 1 visit to the date of the first documented evidence of CR as determined by the investigator. CR was defined as absolute neutrophil count ≥1,000/µL, platelets count ≥100,000/µL, bone marrow blasts \<5% and absence of circulating blasts and blasts with auer rods; absence of extramedullary disease.
| days | Part 2: Tamibarotene/Venetoclax/Azacitidine | Part 2: Venetoclax/Azacitidine |
|---|---|---|
| Part 2: Time to Complete Response | 21.0 (16.0 to 25.0) | 25.0 (19.0 to 43.0) |
Time to CR/CRi was defined as the duration from the date of Cycle 1 Day 1 Visit to the date of the first documented evidence of CR/CRi as determined by the investigator. CR was defined as absolute neutrophil count ≥1,000/µL, platelets count ≥100,000/µL, bone marrow blasts \<5% and absence of circulating blasts and blasts with auer rods; absence of extramedullary disease.CRi was defined as absolute neutrophil count \<1,000/µL, platelets count \<100,000/µL, bone marrow blasts \<5% and all CR criteria met except either neutrophils or platelets not recovered.
| days | Part 2: Tamibarotene/Venetoclax/Azacitidine | Part 2: Venetoclax/Azacitidine |
|---|---|---|
| Part 2: Time to CR/CRi | 21.0 (16.0 to 28.0) | 24.5 (19.0 to 36.0) |
Time to CR/CRh was defined as the duration from the date of Cycle 1 Day 1 Visit to the date of the first documented evidence of CR/CRh as determined by the investigator. CR was defined as absolute neutrophil count ≥1,000/µL, platelets count ≥100,000/µL, bone marrow blasts \<5% and absence of circulating blasts and blasts with auer rods; absence of extramedullary disease. CRh was defined as absolute neutrophil count \>500/µL, platelets count \>500,000/µL, bone marrow blasts \<5% and all CR criteria met except ANC and platelets with partial recovery of peripheral counts.
| days | Part 2: Tamibarotene/Venetoclax/Azacitidine | Part 2: Venetoclax/Azacitidine |
|---|---|---|
| Part 2: Time to CR/CRh | 21.0 (16.0 to 25.0) | 25.0 (19.0 to 43.0) |
ORR: percentage of participants who achieved a overall response as comprised of CR(ANC ≥1,000/µL, platelets count (PC) ≥100,000/µL, bone marrow blasts \<5% and absence of circulating blasts and blasts with auer rods;absence of extramedullary disease),CRi (ANC \<1,000/µL, PC \<100,000/µL, bone marrow blasts \<5% and all CR criteria met except either neutrophils or platelets not recovered), CRh (ANC \>500/µL, PC \>500,000/µL, bone marrow blasts \<5% and all CR criteria met except ANC and platelets with partial recovery of peripheral counts), morphologically leukemia-free state (bone marrow blasts \<5%, absence of blasts with auer rods and \<5% blasts in marrow sample with a count of at least 200 nucleated cells or cellularity ≥10%. Absence of EMD. No hematologic criteria required.), or PR was defined as ANC \<1,000/µL, PC \<100,000/µL, ≥50% decrease from baseline, with decrease to 5-25. ORR was calculated as ORR (%)=number of overall responders/number of participants in the Safety Population×100.
| Percentage of participants | Part 2: Tamibarotene/Venetoclax/Azacitidine | Part 2: Venetoclax/Azacitidine |
|---|---|---|
| Part 2: Overall Response Rate | 80.00 (59.3 to 93.2) | 73.08 (52.2 to 88.4) |
Collected over Up to 3 years. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Part 1: Tamibarotene/Venetoclax/Azacitidine | 7/10 (70%) | 10/10 (100%) | 10/10 (100%) |
| Part 2: Tamibarotene/Venetoclax/Azacitidine | 7/24 (29.2%) | 15/24 (62.5%) | 24/24 (100%) |
| Part 2: Venetoclax/Azacitidine | 7/27 (25.9%) | 13/27 (48.1%) | 24/27 (88.9%) |
| Part 3: Tamibarotene/Venetoclax/Azacitidine | 2/5 (40%) | 4/5 (80%) | 5/5 (100%) |
| Event | Part 1: Tamibarotene/Venetoclax/Azacitidine | Part 2: Tamibarotene/Venetoclax/Azacitidine | Part 2: Venetoclax/Azacitidine | Part 3: Tamibarotene/Venetoclax/Azacitidine |
|---|---|---|---|---|
| Febrile neutropeniaBlood and lymphatic system disorders | 2/10 | 5/24 | 6/27 | 2/5 |
| NeutropeniaBlood and lymphatic system disorders | 3/10 | 0/24 | 1/27 | 0/5 |
| Febrile bone marrow aplasiaBlood and lymphatic system disorders | 0/10 | 0/24 | 0/27 | 1/5 |
| AnaemiaBlood and lymphatic system disorders | 0/10 | 1/24 | 0/27 | 1/5 |
| Febrile bone marrow aplasiaBlood and lymphatic system disorders | 0/10 | 1/24 | 1/27 | 1/5 |
| SepsisInfections and infestations | 2/10 | 2/24 | 1/27 | 0/5 |
| Pulmonary embolismRespiratory, thoracic and mediastinal disorders | 0/10 | 0/24 | 0/27 | 1/5 |
| Non-cardiac chest painGeneral disorders | 1/10 | 0/24 | 1/27 | 0/5 |
| CholecystitisHepatobiliary disorders | 1/10 | 0/24 | 1/27 | 0/5 |
| Bronchopulmonary aspergillosisInfections and infestations | 1/10 | 0/24 | 0/27 | 0/5 |
| Event | Part 1: Tamibarotene/Venetoclax/Azacitidine | Part 2: Tamibarotene/Venetoclax/Azacitidine | Part 2: Venetoclax/Azacitidine | Part 3: Tamibarotene/Venetoclax/Azacitidine |
|---|---|---|---|---|
| ThrombocytopeniaBlood and lymphatic system disorders | 2/10 | 3/24 | 1/27 | 3/5 |
| ConstipationGastrointestinal disorders | 5/10 | 10/24 | 5/27 | 1/5 |
| Decreased appetiteMetabolism and nutrition disorders | 5/10 | 5/24 | 7/27 | 0/5 |
| NeutropeniaBlood and lymphatic system disorders | 2/10 | 5/24 | 8/27 | 2/5 |
| CoughRespiratory, thoracic and mediastinal disorders | 4/10 | 5/24 | 5/27 | 0/5 |
| White blood cell count decreasedInvestigations | 4/10 | 5/24 | 5/27 | 0/5 |
| DiarrhoeaGastrointestinal disorders | 2/10 | 9/24 | 5/27 | 1/5 |
| NauseaGastrointestinal disorders | 3/10 | 7/24 | 9/27 | 0/5 |
| Oedema peripheralGeneral disorders | 3/10 | 6/24 | 2/27 | 0/5 |
| AnxietyPsychiatric disorders | 3/10 | 0/24 | 1/27 | 0/5 |
Part 1 and Part 3 safety population included all enrolled participants who had received any amount of study drug (tamibarotene, venetoclax, or azacitidine). Part 2 intent to treat (ITT) population included all participants who were randomized in Part 2. Treatment groups for this population were determined according to the treatment assignment at the time of randomization. Data of Part 3 participants is being reported separately.
| Age, Categorical(Participants) | Part 1: Tamibarotene/Venetoclax/Azacitidine | Part 2: Tamibarotene/Venetoclax/Azacitidine | Part 2: Venetoclax/Azacitidine | Part 3: Tamibarotene/Venetoclax/Azacitidine | Total |
|---|---|---|---|---|---|
| Part 1 and Part 2 — <=18 years | 0 | 0 | 0 | 0 | 0 |
| Part 1 and Part 2 — Between 18 and 65 years | 4 | 2 | 0 | 0 | 6 |
| Part 1 and Part 2 — >=65 years | 6 | 23 | 26 | 0 | 55 |
| Part 3 — <=18 years | 0 | 0 | 0 | 0 | 0 |
| Part 3 — Between 18 and 65 years | 0 | 0 | 0 | 0 | 0 |
| Part 3 — >=65 years | 0 | 0 | 0 | 5 | 5 |
| Sex: Female, Male(Participants) | Part 1: Tamibarotene/Venetoclax/Azacitidine | Part 2: Tamibarotene/Venetoclax/Azacitidine | Part 2: Venetoclax/Azacitidine | Part 3: Tamibarotene/Venetoclax/Azacitidine | Total |
|---|---|---|---|---|---|
| Part 1 and Part 2 — Female | 6 | 13 | 12 | 0 | 31 |
| Part 1 and Part 2 — Male | 4 | 12 | 14 | 0 | 30 |
| Part 3 — Female | 0 | 0 | 0 | 1 | 1 |
| Part 3 — Male | 0 | 0 | 0 | 4 | 4 |
| Ethnicity (NIH/OMB)(Participants) | Part 1: Tamibarotene/Venetoclax/Azacitidine | Part 2: Tamibarotene/Venetoclax/Azacitidine | Part 2: Venetoclax/Azacitidine | Part 3: Tamibarotene/Venetoclax/Azacitidine | Total |
|---|---|---|---|---|---|
| Part 1 and Part 2 — Hispanic or Latino | 0 | 0 | 0 | 0 | 0 |
| Part 1 and Part 2 — Not Hispanic or Latino | 6 | 11 | 7 | 0 | 24 |
| Part 1 and Part 2 — Unknown or Not Reported | 4 | 14 | 19 | 0 | 37 |
| Part 3 — Hispanic or Latino | 0 | 0 | 0 | 0 | 0 |
| Part 3 — Not Hispanic or Latino | 0 | 0 | 0 | 0 | 0 |
| Part 3 — Unknown or Not Reported | 0 | 0 | 0 | 5 | 5 |
| Race (NIH/OMB)(Participants) | Part 1: Tamibarotene/Venetoclax/Azacitidine | Part 2: Tamibarotene/Venetoclax/Azacitidine | Part 2: Venetoclax/Azacitidine | Part 3: Tamibarotene/Venetoclax/Azacitidine | Total |
|---|---|---|---|---|---|
| Part 1 and Part 2 — American Indian or Alaska Native | 1 | 1 | 0 | 0 | 2 |
| Part 1 and Part 2 — Asian | 0 | 0 | 0 | 0 | 0 |
| Part 1 and Part 2 — Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 |
| Part 1 and Part 2 — Black or African American | 2 | 2 | 0 | 0 | 4 |
| Part 1 and Part 2 — White | 4 | 8 | 7 | 0 | 19 |
| Part 1 and Part 2 — More than one race | 0 | 0 | 0 | 0 | 0 |
| Part 1 and Part 2 — Unknown or Not Reported | 3 | 14 | 19 | 0 | 36 |
| Part 3 — American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 |
| Part 3 — Asian | 0 | 0 | 0 | 0 | 0 |
| Part 3 — Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 |
| Part 3 — Black or African American | 0 | 0 | 0 | 0 | 0 |
| Part 3 — White | 0 | 0 | 0 | 0 | 0 |
| Part 3 — More than one race | 0 | 0 | 0 | 0 | 0 |
| Part 3 — Unknown or Not Reported | 0 | 0 | 0 | 5 | 5 |
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Studies of the drug tested here: Tamibarotene
Syros Pharmaceuticals