Safety, Tolerability, Pharmacokinetics, and Efficacy of AZD2811 Nanoparticles as Monotherapy or in Combination in Acute Myeloid Leukemia Participants.

Inclusion criteria 1. AML participants who have either: (a) relapsed or are refractory to standard therapies (the participant may have been treated with standard therapy prior to the diagnosis of AML e.g. for MDS), OR (b) diagnosis of AML (bone marrow blasts ≥ 20%), who are previously untreated for AML, and are not suitable for intensive induction therapy, as defined below (for AZD2811 monotherapy and HMA combination participants only i.e. inclusion criteria 1(b) may only be used to enrol a participant into Groups 1 and 2; previously untreated AML participants may not enrol into Group 3 unless they fulfil inclusion criteria 1(a) above). Participants are unsuitable for intensive induction therapy if they are: * 75 years or * 75 years of age with clinically significant cardiac or pulmonary dysfunction unrelated to leukaemia, as reflected by at least 1 of the following criteria: Left ventricular ejection fraction (LVEF) ≤50% Diffusing capacity of the lungs for carbon monoxide (DLCO) ≤65% of expected Forced expiratory volume 1(FEV1) ≤65% of expected Chronic stable angina any significant co-morbidities which in the opinion of the treating physician makes the participant unsuitable for intensive induction therapy. This must be documented by the study monitor. 2. AML participants who are unlikely to demonstrate rapid progression such that they would be unable to complete the first cycle of therapy. 3. Provision of signed and dated, written informed consent prior to any study-specific procedures, sampling and analyses. 4. Aged at least 18 years 5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2. 6. Prior treatment with hydroxyurea (up to 24 hours before study treatment) is allowed 7. Adequate organ system function as outlined below: Prothrombin time (PT)/partial thromboplastin time (PTT) ≤1.5 x upper limit of normal (ULN) Total bilirubin ≤1.5 x ULN. Participants with documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) who have serum bilirubin ≤3 x the ULN may be enrolled, unless there is evidence of hemolytic anemia Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ˂2.5 x ULN if no liver involvement or ≤5 times the ULN with liver involvement Creatinine ≤1.5 x ULN, OR calculated or measured creatinine clearance ≥50 mL/min as calculated by the Cockcroft-Gault method, OR 24-hour measured urine creatinine clearance ≥50 mL/min. Participants enrolled in the venetoclax combination part with a creatinine clearance (CLcr) \<80 mL/min (and ≥ 45 mL/min) as calculated by Cockcroft-Gault should be able to have more intensive prophylaxis and monitoring (according to institutional standard) to reduce the risk of tumour lysis syndrome (TLS) when initiating treatment with venetoclax. 8. Females should be using adequate contraception, should not be breast feeding and must have a negative serum pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening: a) Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments, b) have documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation. 9 Sexually active male participants should be willing to use barrier contraception i.e., condoms. Female partners of male participants should also use a highly effective form of contraception if they are of childbearing potential, unless the male participant is abstaining from sexual intercourse. Exclusion criteria 1. Treatment with any of the following: Any investigational agents, experimental antibody or antibody drug conjugates, or study drugs from a previous clinical study within 3-4 weeks of said prior investigational agent(s) with regard to the first dose of study treatment on this clinical study protocol. Any other chemotherapy (except hydroxyurea), immunotherapy or anticancer agents within 2 weeks of the first dose of study treatment Any haematopoietic growth factors (e.g., filgrastim \[G-CSF\] or sargramostim \[GM-CSF\]) within 7 days of the first dose of AZD2811 monotherapy or with combination agent(s) or pegylated G-CSF (pegfilgrastim) or darbepoetin within 14 days of the first dose of study treatment Prescription or non-prescription drugs or other products known to be strong inhibitors/inducers of CYP3A that cannot be discontinued prior to Day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study drug. Washout periods should be a minimum of 5 half-lives depending on the medication. Participants who have undergone allogeneic stem cell transplant within 12 months are excluded. If allogeneic transplant was \>12 months ago, then they are not excluded as long as they are off all immunosuppression and have no signs or symptoms of active graft versus host disease. Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study treatment 2. With the exception of alopecia, any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment . 3. Presence of, or history of leptomeningeal disease. 4. As judged by the Investigator, any evidence of: severe or uncontrolled systemic diseases (e.g., severe hepatic impairment, interstitial lung disease \[bilateral, diffuse, parenchymal lung disease\]) or other malignancy (like advanced malignant hepatic tumours); current unstable or uncompensated respiratory or cardiac conditions; or uncontrolled hypertension; history of, or active, bleeding diatheses (e.g., haemophilia or von Willebrand disease); participants with inflammatory bowel disease (e.g., Crohn or colitis ulcerosa); uncontrolled active systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment); or IV anti-infective treatment within 2 weeks before first dose of study treatment unless either clear evidence would indicate that despite the clinical symptoms no infection took place, or just a single dose of IV antibiotics was administered followed by oral treatment thereafter. 5. Any of the following cardiac criteria: a) Congestive heart failure (CHF) per New York Heart Association (NYHA) classification \> Class II, b) Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy, c) Unstable angina or new-onset angina, d) QTcF interval \>450 ms (for male participants) or \>470 ms (for female participants) on screening electrocardiogram (ECG). 6. Active non-infectious skin disease (including rash, dermatitis, or psoriasis, but excluding stable plaque psoriasis from the definition of active disease). Participants with a rash that is biopsy-proven leukaemia or with pressure ulcers are not excluded. Participants with petechiae from thrombocytopenia or participants with drug related rashes that are improving are not excluded.. 7. Participants with a known hypersensitivity to azacitidine or mannitol (HMA combination participants only). 8. History of hypersensitivity to active or inactive excipients (e.g., PEG) of any drug in the study or drugs with a similar chemical structure or class to those investigated in the study. 9. Known history of infection with human immunodeficiency virus (HIV) 10. Serologic status reflecting active hepatitis B or C infection: 1. Participants who are anti-HBc positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR) result before enrolment. Those who are hepatitis B surface antigen positive or hepatitis B PCR positive will be excluded. 2. Participants who are hepatitis C antibody positive will need to have a negative PCR result before enrolment. Those who are hepatitis C PCR positive will be excluded. Additional exclusion criteria - venetoclax combination 1. Adults with previously untreated diagnosis of AML (bone marrow blasts ≥ 20%), unless they fulfil inclusion criterion 1(a) above. 2. White blood cell (WBC) count \> 25,000 cells/mm\^3 (25 x 10\^9/L); use of leukapheresis or hydroxyurea before venetoclax initiation is allowed to achieve this entry criterion (leukapheresis or hydroxyurea must be stopped at least 48 hours before the initiation of venetoclax). 3. AML with known active central nervous system involvement. 4. Chronic respiratory disease that requires continuous oxygen use. 5. Previous venetoclax exposure that ended due to venetoclax toxicity. 6. Use of moderate CYP3A inhibitor/inducers and P-gP inhibitors, with the exception of fluconazole and isavuconazole, that cannot be discontinued prior to Day 1 of dosing. Washout periods should be a minimum of 5 half-lives depending on the medication unless agreed upon with the Sponsor. 7. Participant consumed grapefruit, grapefruit products, Seville oranges (including marmalades containing Seville oranges) or star fruit within 3 days before the initiation of venetoclax.