Trial Outcomes & Findings for Tamibarotene Plus Venetoclax/Azacitidine in Participants With Newly Diagnosed Acute Myeloid Leukemia (AML) (NCT NCT04905407)

Last Updated: 2025-02-24

Results Overview

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'.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

66 participants

Primary outcome timeframe

Up to 3 years

Results posted on

2025-02-24

Participant Flow

As per sponsor decision, the study was terminated.

Participant milestones

Participant milestones
Measure	Part 1: Tamibarotene/Venetoclax/Azacitidine Participants received 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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 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 was administered to participants who have been confirmed as retinoic acid receptor alpha (RARA)-positive.	Part 2: Tamibarotene/Venetoclax/Azacitidine Participants received tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle.	Part 2: Venetoclax/Azacitidine Participants received venetoclax/azacitidine combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond.	Part 3: Tamibarotene/Venetoclax/Azacitidine Part 2 participants treated with venetoclax/azacitidine combination (Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond) who experienced progressive disease, relapse after initial Complete Remission (CR) or Complete Remission With Incomplete Hematologic Recovery (CRi) response, or treatment failure received subsequent treatment in Part 3, where tamibarotene (6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle) was added to their regimen.
Part 1 and Part 2 STARTED	10	25	26	0
Part 1 and Part 2 Received at Least 1 Dose of Study Drug	10	25	26	0
Part 1 and Part 2 Intent to Treat Analysis Set	0	25	26	0
Part 1 and Part 2 Safety Analysis Set	10	24	27	0
Part 1 and Part 2 Modified Intent-to-Treat (mITT) Analysis Set	0	25	26	0
Part 1 and Part 2 Response Evaluable Population	9	0	0	0
Part 1 and Part 2 COMPLETED	1	17	17	0
Part 1 and Part 2 NOT COMPLETED	9	8	9	0
Part 3 STARTED	0	0	0	5
Part 3 Received at Least 1 Dose of Study Drug	0	0	0	5
Part 3 Safety Analysis Set	0	0	0	5
Part 3 COMPLETED	0	0	0	3
Part 3 NOT COMPLETED	0	0	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1: Tamibarotene/Venetoclax/Azacitidine Participants received 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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 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 was administered to participants who have been confirmed as retinoic acid receptor alpha (RARA)-positive.	Part 2: Tamibarotene/Venetoclax/Azacitidine Participants received tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle.	Part 2: Venetoclax/Azacitidine Participants received venetoclax/azacitidine combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond.	Part 3: Tamibarotene/Venetoclax/Azacitidine Part 2 participants treated with venetoclax/azacitidine combination (Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond) who experienced progressive disease, relapse after initial Complete Remission (CR) or Complete Remission With Incomplete Hematologic Recovery (CRi) response, or treatment failure received subsequent treatment in Part 3, where tamibarotene (6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle) was added to their regimen.
Part 1 and Part 2 Withdrawal by Subject	2	1	1	0
Part 1 and Part 2 Death	7	7	7	0
Part 1 and Part 2 Other than specified	0	0	1	0
Part 3 Death	0	0	0	2

Baseline Characteristics

The baseline characteristics data of Part 3 participants are reported separately.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1: Tamibarotene/Venetoclax/Azacitidine n=10 Participants Participants received tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle. Tamibarotene was administered to participants who have been confirmed as RARA-positive.	Part 2: Tamibarotene/Venetoclax/Azacitidine n=25 Participants Participants received tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle.	Part 2: Venetoclax/Azacitidine n=26 Participants Participants received venetoclax/azacitidine combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond.	Part 3: Tamibarotene/Venetoclax/Azacitidine n=5 Participants Part 2 participants treated with venetoclax/azacitidine combination (Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond) who experienced progressive disease, relapse after initial CR or CRi response, or treatment failure received subsequent treatment in Part 3, where tamibarotene (6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle) was added to their regimen.	Total n=66 Participants Total of all reporting groups
Age, Categorical Part 1 and Part 2 · <=18 years	0 Participants n=10 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=25 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=26 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=61 Participants • The baseline characteristics data of Part 3 participants are reported separately.
Age, Categorical Part 1 and Part 2 · Between 18 and 65 years	4 Participants n=10 Participants • The baseline characteristics data of Part 3 participants are reported separately.	2 Participants n=25 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=26 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	6 Participants n=61 Participants • The baseline characteristics data of Part 3 participants are reported separately.
Age, Categorical Part 1 and Part 2 · >=65 years	6 Participants n=10 Participants • The baseline characteristics data of Part 3 participants are reported separately.	23 Participants n=25 Participants • The baseline characteristics data of Part 3 participants are reported separately.	26 Participants n=26 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	55 Participants n=61 Participants • The baseline characteristics data of Part 3 participants are reported separately.
Age, Categorical Part 3 · <=18 years	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=5 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=5 Participants • The baseline characteristics data of Part 3 participants are reported separately.
Age, Categorical Part 3 · Between 18 and 65 years	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=5 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=5 Participants • The baseline characteristics data of Part 3 participants are reported separately.
Age, Categorical Part 3 · >=65 years	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	5 Participants n=5 Participants • The baseline characteristics data of Part 3 participants are reported separately.	5 Participants n=5 Participants • The baseline characteristics data of Part 3 participants are reported separately.
Sex: Female, Male Part 1 and Part 2 · Female	6 Participants n=10 Participants • The baseline characteristics data of Part 3 participants are reported separately.	13 Participants n=25 Participants • The baseline characteristics data of Part 3 participants are reported separately.	12 Participants n=26 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	31 Participants n=61 Participants • The baseline characteristics data of Part 3 participants are reported separately.
Sex: Female, Male Part 1 and Part 2 · Male	4 Participants n=10 Participants • The baseline characteristics data of Part 3 participants are reported separately.	12 Participants n=25 Participants • The baseline characteristics data of Part 3 participants are reported separately.	14 Participants n=26 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	30 Participants n=61 Participants • The baseline characteristics data of Part 3 participants are reported separately.
Sex: Female, Male Part 3 · Female	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	1 Participants n=5 Participants • The baseline characteristics data of Part 3 participants are reported separately.	1 Participants n=5 Participants • The baseline characteristics data of Part 3 participants are reported separately.
Sex: Female, Male Part 3 · Male	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	4 Participants n=5 Participants • The baseline characteristics data of Part 3 participants are reported separately.	4 Participants n=5 Participants • The baseline characteristics data of Part 3 participants are reported separately.
Ethnicity (NIH/OMB) Part 1 and Part 2 · Hispanic or Latino	0 Participants n=10 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=25 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=26 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=61 Participants • The baseline characteristics data of Part 3 participants are reported separately.
Ethnicity (NIH/OMB) Part 1 and Part 2 · Not Hispanic or Latino	6 Participants n=10 Participants • The baseline characteristics data of Part 3 participants are reported separately.	11 Participants n=25 Participants • The baseline characteristics data of Part 3 participants are reported separately.	7 Participants n=26 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	24 Participants n=61 Participants • The baseline characteristics data of Part 3 participants are reported separately.
Ethnicity (NIH/OMB) Part 1 and Part 2 · Unknown or Not Reported	4 Participants n=10 Participants • The baseline characteristics data of Part 3 participants are reported separately.	14 Participants n=25 Participants • The baseline characteristics data of Part 3 participants are reported separately.	19 Participants n=26 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	37 Participants n=61 Participants • The baseline characteristics data of Part 3 participants are reported separately.
Ethnicity (NIH/OMB) Part 3 · Hispanic or Latino	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=5 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=5 Participants • The baseline characteristics data of Part 3 participants are reported separately.
Ethnicity (NIH/OMB) Part 3 · Not Hispanic or Latino	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=5 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=5 Participants • The baseline characteristics data of Part 3 participants are reported separately.
Ethnicity (NIH/OMB) Part 3 · Unknown or Not Reported	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	5 Participants n=5 Participants • The baseline characteristics data of Part 3 participants are reported separately.	5 Participants n=5 Participants • The baseline characteristics data of Part 3 participants are reported separately.
Race (NIH/OMB) Part 1 and Part 2 · American Indian or Alaska Native	1 Participants n=10 Participants • The baseline characteristics data of Part 3 participants are reported separately.	1 Participants n=25 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=26 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	2 Participants n=61 Participants • The baseline characteristics data of Part 3 participants are reported separately.
Race (NIH/OMB) Part 1 and Part 2 · Asian	0 Participants n=10 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=25 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=26 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=61 Participants • The baseline characteristics data of Part 3 participants are reported separately.
Race (NIH/OMB) Part 1 and Part 2 · Native Hawaiian or Other Pacific Islander	0 Participants n=10 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=25 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=26 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=61 Participants • The baseline characteristics data of Part 3 participants are reported separately.
Race (NIH/OMB) Part 1 and Part 2 · Black or African American	2 Participants n=10 Participants • The baseline characteristics data of Part 3 participants are reported separately.	2 Participants n=25 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=26 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	4 Participants n=61 Participants • The baseline characteristics data of Part 3 participants are reported separately.
Race (NIH/OMB) Part 1 and Part 2 · White	4 Participants n=10 Participants • The baseline characteristics data of Part 3 participants are reported separately.	8 Participants n=25 Participants • The baseline characteristics data of Part 3 participants are reported separately.	7 Participants n=26 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	19 Participants n=61 Participants • The baseline characteristics data of Part 3 participants are reported separately.
Race (NIH/OMB) Part 1 and Part 2 · More than one race	0 Participants n=10 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=25 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=26 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=61 Participants • The baseline characteristics data of Part 3 participants are reported separately.
Race (NIH/OMB) Part 1 and Part 2 · Unknown or Not Reported	3 Participants n=10 Participants • The baseline characteristics data of Part 3 participants are reported separately.	14 Participants n=25 Participants • The baseline characteristics data of Part 3 participants are reported separately.	19 Participants n=26 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	36 Participants n=61 Participants • The baseline characteristics data of Part 3 participants are reported separately.
Race (NIH/OMB) Part 3 · American Indian or Alaska Native	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=5 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=5 Participants • The baseline characteristics data of Part 3 participants are reported separately.
Race (NIH/OMB) Part 3 · Asian	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=5 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=5 Participants • The baseline characteristics data of Part 3 participants are reported separately.
Race (NIH/OMB) Part 3 · Native Hawaiian or Other Pacific Islander	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=5 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=5 Participants • The baseline characteristics data of Part 3 participants are reported separately.
Race (NIH/OMB) Part 3 · Black or African American	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=5 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=5 Participants • The baseline characteristics data of Part 3 participants are reported separately.
Race (NIH/OMB) Part 3 · White	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=5 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=5 Participants • The baseline characteristics data of Part 3 participants are reported separately.
Race (NIH/OMB) Part 3 · More than one race	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=5 Participants • The baseline characteristics data of Part 3 participants are reported separately.	0 Participants n=5 Participants • The baseline characteristics data of Part 3 participants are reported separately.
Race (NIH/OMB) Part 3 · Unknown or Not Reported	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	0 Participants The baseline characteristics data of Part 3 participants are reported separately.	5 Participants n=5 Participants • The baseline characteristics data of Part 3 participants are reported separately.	5 Participants n=5 Participants • The baseline characteristics data of Part 3 participants are reported separately.

PRIMARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Part 2: Tamibarotene/Venetoclax/Azacitidine n=10 Participants Participants received tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle.	Part 2: Venetoclax/Azacitidine Participants received tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle.
Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)	10 Participants	—

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part 2: Tamibarotene/Venetoclax/Azacitidine n=25 Participants Participants received tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle.	Part 2: Venetoclax/Azacitidine n=26 Participants Participants received tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle.
Part 2: Complete Remission/Complete Remission With Incomplete Hematologic Recovery (CR/CRi) Rate	60.00 Percentage of participants Interval 38.7 to 78.9	69.23 Percentage of participants Interval 48.2 to 85.7

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part 2: Tamibarotene/Venetoclax/Azacitidine n=9 Participants Participants received tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle.	Part 2: Venetoclax/Azacitidine Participants received tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle.
Part 1: Overall Response Rate (ORR)	77.78 Percentage of participants Interval 40.0 to 97.2	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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).

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'.

Outcome measures

Outcome measures
Measure	Part 2: Tamibarotene/Venetoclax/Azacitidine n=24 Participants Participants received tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle.	Part 2: Venetoclax/Azacitidine n=27 Participants Participants received tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle.
Part 2: Number of Participants With Treatment Emergent Adverse Events	24 Participants	24 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part 2: Tamibarotene/Venetoclax/Azacitidine n=25 Participants Participants received tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle.	Part 2: Venetoclax/Azacitidine n=26 Participants Participants received tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle.
Part 2: Complete Remission (CR) Rate	48.00 Percentage of participants Interval 27.8 to 68.7	57.69 Percentage of participants Interval 36.9 to 76.6

SECONDARY outcome

Timeframe: 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/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.

Outcome measures

Outcome measures
Measure	Part 2: Tamibarotene/Venetoclax/Azacitidine n=25 Participants Participants received tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle.	Part 2: Venetoclax/Azacitidine n=26 Participants Participants received tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle.
Part 2: Complete Remission/ Complete Remission With Partial Hematologic Recovery (CR/CRh) Rate	48.00 Percentage of participants Interval 32.2 to 75.6	57.69 Percentage of participants Interval 42.7 to 83.6

SECONDARY outcome

Timeframe: 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 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.

Outcome measures

Outcome measures
Measure	Part 2: Tamibarotene/Venetoclax/Azacitidine n=4 Participants Participants received tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle.	Part 2: Venetoclax/Azacitidine n=6 Participants Participants received tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle.
Part 2: Duration of Complete Remission	293.0 days Interval 66.0 to The upper limit of 95% confidence interval (CI) could not be calculated due to smaller number of participants with an event.	256.5 days Interval 56.0 to The upper limit of 95% CI could not be calculated due to smaller number of participants with an event.

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part 2: Tamibarotene/Venetoclax/Azacitidine n=5 Participants Participants received tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle.	Part 2: Venetoclax/Azacitidine n=8 Participants Participants received tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle.
Part 2: Duration of CR/CRi	293.0 days Interval 66.0 to The upper limit of 95% CI could not be calculated due to smaller number of participants with an event.	253.0 days Interval 56.0 to 263.0

SECONDARY outcome

Timeframe: Up to 3 years

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.

Outcome measures

Outcome measures
Measure	Part 2: Tamibarotene/Venetoclax/Azacitidine n=4 Participants Participants received tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle.	Part 2: Venetoclax/Azacitidine n=6 Participants Participants received tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle.
Part 2: Duration of CR/CRh	293.0 days Interval 66.0 to The upper limit of 95% CI could not be calculated due to smaller number of participants with an event.	256.5 days Interval 56.0 to The upper limit of 95% CI could not be calculated due to smaller number of participants with an event.

SECONDARY outcome

Timeframe: Up to 3 years

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.

Outcome measures

Outcome measures
Measure	Part 2: Tamibarotene/Venetoclax/Azacitidine n=12 Participants Participants received tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle.	Part 2: Venetoclax/Azacitidine n=15 Participants Participants received tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle.
Part 2: Time to Complete Response	21.0 days Interval 16.0 to 25.0	25.0 days Interval 19.0 to 43.0

SECONDARY outcome

Timeframe: Up to 3 years

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.

Outcome measures

Outcome measures
Measure	Part 2: Tamibarotene/Venetoclax/Azacitidine n=15 Participants Participants received tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle.	Part 2: Venetoclax/Azacitidine n=18 Participants Participants received tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle.
Part 2: Time to CR/CRi	21.0 days Interval 16.0 to 28.0	24.5 days Interval 19.0 to 36.0

SECONDARY outcome

Timeframe: Up to 3 years

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.

Outcome measures

Outcome measures
Measure	Part 2: Tamibarotene/Venetoclax/Azacitidine n=12 Participants Participants received tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle.	Part 2: Venetoclax/Azacitidine n=15 Participants Participants received tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle.
Part 2: Time to CR/CRh	21.0 days Interval 16.0 to 25.0	25.0 days Interval 19.0 to 43.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part 2: Tamibarotene/Venetoclax/Azacitidine n=25 Participants Participants received tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle.	Part 2: Venetoclax/Azacitidine n=26 Participants Participants received tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 mg/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) was permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing was 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg BID orally, on Days 8 through 28 of each 28-day therapy cycle.
Part 2: Overall Response Rate	80.00 Percentage of participants Interval 59.3 to 93.2	73.08 Percentage of participants Interval 52.2 to 88.4

Adverse Events

Part 1: Tamibarotene/Venetoclax/Azacitidine

Serious events: 10 serious events

Other events: 10 other events

Deaths: 7 deaths

Part 2: Tamibarotene/Venetoclax/Azacitidine

Serious events: 15 serious events

Other events: 24 other events

Deaths: 7 deaths

Part 2: Venetoclax/Azacitidine

Serious events: 13 serious events

Other events: 24 other events

Deaths: 7 deaths

Part 3: Tamibarotene/Venetoclax/Azacitidine

Serious events: 4 serious events

Other events: 5 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Tiffany Crowell

Syros Pharmaceuticals

Phone: 617-674-9069

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Note that the agreements are between the clinical sites and the Sponsor (or its agents), which restrict the clinical trial sites' rights to discuss or publish trial results after the trial is completed.
Publication restrictions are in place

Restriction type: OTHER