Tamibarotene Plus Venetoclax/Azacitidine in Participants With Newly Diagnosed Acute Myeloid Leukemia (AML)

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

Population: Part 1 Safety Analysis Set included all enrolled participants who received any amount of study treatment (tamibarotene, venetoclax, or azacitidine).

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

Population: Part 2 mITT Analysis Set included all RARA-positive participants who were randomized in Part 2 and started dosing from Cycle 1 Day 1.

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

Population: Part 1 response evaluable population included all RARA-positive participants enrolled in Part 1 who had received any amount of study drug (tamibarotene, venetoclax, or azacitidine) and had either completed at least 1 response assessment or have discontinued treatment due to clinical progression/progressive disease prior to any response assessments.

Time frame: Day 8 and 22 of Cycle 1, Day 15 of Cycles 2 and 3 (cycle length = 28 days)

Population: While blood samples were collected to derive data for the planned PK outcome measures, the study was terminated prior to that data being generated, analyzed, summarized, or made available by the study sponsor. Therefore, no PK data can be presented here.

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

Population: Part 2 mITT population included all RARA-positive participants who were randomized in Part 2 and started dosing from Cycle 1 Day 1.

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

Population: Part 2 mITT population included all RARA-positive participants who were randomized in Part 2 and started dosing from Cycle 1 Day 1.

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

Population: Part 2 mITT population included all RARA-positive participants who were randomized in Part 2 and started dosing from Cycle 1 Day 1. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

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

Population: Part 2 mITT population included all RARA-positive participants who were randomized in Part 2 and started dosing from Cycle 1 Day 1. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

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

Population: Part 2 mITT Population included all RARA-positive participants who were randomized in Part 2 and started dosing from Cycle 1 Day 1. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

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

Population: Part 2 safety population included all randomized participants who had received any amount of study drug (tamibarotene, venetoclax, or azacitidine).

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

Population: Part 2 mITT Population included all RARA-positive participants who were randomized in Part 2 and started dosing from Cycle 1 Day 1.

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

Population: Part 2 mITT population included all RARA-positive participants who were randomized in Part 2 and started dosing from Cycle 1 Day 1. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

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

Population: Part 2 mITT population included all RARA-positive participants who were randomized in Part 2 and started dosing from Cycle 1 Day 1. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

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

Population: Part 2 mITT Population included all RARA-positive participants who were randomized in Part 2 and started dosing from Cycle 1 Day 1. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.