The purpose of this study is as follows:

1. Determine whether people receiving the combination treatment of olutasidenib, venetoclax, and azacitidine have the same, more, or fewer side effects compared to the usual chemotherapy treatment that people with this condition receive.
2. Determine how well the combination treatment of olutasidenib, venetoclax, and azacitidine works compared to the usual chemotherapy treatment that people with this condition receive.

Inclusion Criteria:

1. Participant is an adult male or female participant aged 18-75 years considered eligible to undergo intensive induction chemotherapy at the time of signing the informed consent form (ICF).

2. Eastern Cooperative Oncology Group (ECOG) performance status ≤2

3. Confirmed diagnosis of:

   1. Newly diagnosed AML Isocitrate dehydrogenase 1 (IDH1) R132 mutated disease as assessed locally. Note: historical results from within 30 days of informed consent will be accepted if the participant did not receive systemic treatment after collection.
   2. Secondary AML, including prior hypomethylating agents (HMA) exposure for myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPN), or MDS/MPN is allowed.

4. Participant must have adequate organ function, defined by the following:

   1. Aspartate transaminase (AST) and alanine aminotransferase (ALT) values ≤3 × upper limit of normal (ULN) or ≤5 × ULN for participants with leukemic involvement.
   2. Bilirubin ≤2 ULN (≤3 × ULN in participants with Gilbert Syndrome) or ≤3 × ULN for participants with leukemic involvement.
   3. Creatinine clearance ≥30 mL/min (using Cockcroft-Gault), or serum creatinine ≤1.5 × ULN.

5. The interval from prior treatment for an antecedent hematologic disorder to the first dose of study treatment (C1D1) will be at least 7 days for cytotoxic or non-cytotoxic (immunotherapy) agents. In addition, the following will be allowed:

   1. Intrathecal chemotherapy for prophylactic use or for controlled central nervous system (CNS) leukemia.
   2. Use of hydroxyurea for participants with rapidly proliferative disease is allowed before the start of study therapy and for the first 4 weeks on study treatment.

6. Recovery from non-hematologic toxic effects of prior treatment to Grade ≤1, or baseline value according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 classification (excluding infertility, alopecia, or Grade 1 neuropathy).

7. Baseline QT interval corrected using the Fridericia equation (QTcF) ≤ 480 msec. Note: This criterion does not apply to participants with a bundle branch block (BBB); for participants with BBB, a cardiology consult is recommended to ensure that QTcF is not prolonged.

8. Female participants who are women of childbearing potential (WOCBP) must have a negative serum or urine (beta-human chorionic gonadotropin (βhCG)) pregnancy test at screening and negative serum or urine test documented within the 24-hour period prior to the first dose of study drug. WOCBP are defined as sexually mature women without prior hysterectomy or who have had any evidence of menses in the past 12 months. However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anti-estrogens, or ovarian suppression (Section 4.8.1).

9. Sexually active female participants who are WOCBP and male participants who are sexually active partners of WOCBP must agree to use a highly effective method of contraception during the course of the study from the date of informed consent and for at least 3 months after their last dose of study drug. Effective birth control methods include the following:

   1. Intrauterine device (IUD) plus one barrier method.
   2. Stable doses of hormonal contraception for at least 3 months (eg, oral, injectable, implant, transdermal).
   3. 2 barrier methods; effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm).
   4. A vasectomized partner (where vasectomy was done at least 4 months prior to first dose of study treatment).
   5. True abstinence (ie, abstinence that is in line with the preferred and usual lifestyle of the participant).

10. Female and male participants must agree to refrain from egg/ova retrieval either for their own use or donation or from sperm donation, respectively, from the date of informed consent until 3 months after the last dose of study treatment.

11. Participant is willing and able to participate and comply with all study requirements and to provide signed and dated written informed consent prior to initiation of any study procedures.

Exclusion Criteria:

1. Relapsed/Refractory AML.
2. ELN (2022) favorable risk AML, except for nucleophosmin 1 (NPM1) mutated AML, which is allowed.
3. Acute promyelocytic leukemia (APL).
4. Positive Fms related receptor tyrosine kinase 3-Internal tandem duplication (FLT3-ITD) mutation.
5. Active CNS involvement by leukemia (other extramedullary disease is allowed).
6. Participants <18 years or >75 years of age.
7. Female participant who is pregnant or breastfeeding.
8. Participant plans to become pregnant or father a child (including ova or sperm donation) while enrolled in this study or within 3 months after last dose of study treatment (Section 4.8).
9. Participant has a known allergy or history of hypersensitivity to study drugs or their excipients.
10. Previous therapy with olutasidenib (or ivosidenib or other IDH1 inhibitor) or venetoclax (or another B cell lymphoma 2 (BCL-2) inhibitor).
11. Participant has active evidence of clinically significant unstable medical condition such as uncontrolled infection, severe metabolic abnormality, poorly controlled psychiatric illness, or symptomatic coronary artery disease (other than stable angina), which could place the participant at unacceptable risk of study treatment, per the Investigator's judgement.
12. Participants receiving treatment with strong Cytochrome P450, family 3, subfamily A (CYP3A) inhibitors within 7 to 14 days or 5 half-lives (whichever is longer) prior to the first dose of study medication. Azoles are allowed with appropriate venetoclax dose reductions. Please note that participants receiving these medications would qualify for this study after undergoing a washout period of 7 to 14 days or 5 half-lives, whatever is longer for the inhibitor/inducer.
13. Participants receiving treatment with strong CYP3A inducers within 7 to 14 days or 5 half-lives (whichever is longer) prior to the first dose of study medication. Please note that participants receiving these medications would qualify for this study after undergoing a washout period of 7 to 14 days or 5 half-lives, whatever is longer for the inhibitor/inducer.
14. History of allogeneic hematopoietic stem cell transplant (HSCT) for a diagnosis other than AML if there is clinically significant active graft-versus-host disease (GVHD) or ongoing immunosuppressive therapy is required beyond prednisone 10 mg daily or equivalent. Otherwise, prior allogeneic HSCT is allowed.
15. Participants with a concurrent active malignancy under treatment.
16. Known history of active hepatitis B (HBV) or hepatitis C (HCV) infection or human immunodeficiency virus (HIV) infection (clinically detectable viral load).
17. Major surgery within 28 days prior to the first dose. Participants must have recovered from surgery and be without current complications.
18. Participants with impaired decision-making capacity.