Acute Myelogenous Leukemia, Myelodysplastic Syndrome
Conditions
Keywords
High Risk Myelodysplastic Syndrome, Relapsed/Refractory, Newly Diagnosed, Unfit for Chemotherapy
Brief summary
This study will take place in parts: * Dose Escalation (Part 1): Participants receive milademetan alone with different dose schedules * Dose Escalation (Part 1A): Participants receive milademetan in combination with 5-azacytidine (AZA), with different dose schedules The recommended dose for Part 2 will be selected. * Dose Expansion (Part 2): After Part 1A, participants will receive the recommended Part 2 dose schedule. There will be three groups - those with: 1. refractory or relapsed acute myelogenous leukemia (AML) 2. newly diagnosed AML unfit for intensive chemotherapy 3. high-risk myelodysplastic syndrome (MDS) * End-of-Study Follow-Up: Safety information will be collected until 30 days after the last treatment. This is the end of the study. The recommended dose for the next study will be selected.
Detailed description
The primary analysis will occur after all participants have either discontinued the study or completed at least 6 months of treatment. After the primary analysis, the main study will be closed. Participants who are still on study at least 6 months after enrollment of the last participant in the study may be eligible to continue receiving study drug in a separate extension phase of the protocol
Interventions
DRUGMilademetan
Milademetan will be administered daily as oral capsules or as a combination of multiple oral capsules containing 5 mg, 20 mg, 80 mg, and/or 200 mg
DRUGAZA
AZA will be administered at 75 mg/m\^2 subcutaneously or intravenously
Sponsors
Daiichi Sankyo
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Parts 1 and 1A are sequential, then Part 2 is parallel
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Has a diagnosis of refractory or relapsed (R/R) AML or high-risk MDS: * Part 1 and 1A (Dose Escalation) * Participants with R/R AML, OR * Participants with untreated, high-risk MDS or participants who have received prior MDS treatment regimens. * Participants ≥18 years old. * Part 2 (Dose Expansion) * Cohort 1: R/R AML * Participants who have treatment failure to prior AML therapy or have relapsed after prior AML therapy. * Participants ≥18 years old. * Cohort 2: Newly diagnosed AML * Participants with newly diagnosed AML who are ineligible for intensive induction chemotherapy. Participants must have had no prior AML treatment, with the exceptions of therapy for antecedent hematologic malignancies or hydroxyurea. * Participants ≥75 years old, OR Participants between 18 and 74 years old (inclusive) with at least one of the specific protocol-defined comorbidities. * Cohort 3: High-risk MDS * Participants with untreated, high-risk MDS or who received up to 2 prior MDS treatment regimens. 2. Has an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. * As an exception, participants with newly diagnosed AML between 18 and 74 years old (inclusive) in Part 2 Cohort 2 with ECOG Performance Status of 3 will be eligible. 3. Has protocol-defined adequate renal, hepatic and blood clotting functions. 4. Is able to provide written informed consent (or authorized representative), comply with protocol visits and procedures, and take oral medication, and does not have any active infection or comorbidity that would interfere with therapy. 5. If female, is either postmenopausal (no menstrual period for a minimum of 12 months), surgically sterile, or, if of childbearing potential, has a negative serum pregnancy test upon entry into this study and is willing to use maximally effective birth control during the period of therapy and for 6 months following the last investigational drug dose. * If male, is surgically sterile or willing to use a maximally effective double-barrier contraception method upon enrollment, during the course of the study, and for 6 months following the last investigational drug dose. 6. Is fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects). 7. Signs and dates an Institutional Review Board-approved informed consent form (including Health Insurance Portability and Accountability Act authorization, if applicable) before performance of any study-specific procedures or tests. 8. Is able and willing to provide bone marrow biopsies/aspirates as requested by the protocol. 9. Is willing to undergo malignancy genotyping for TP53 mutation, insertion, or deletion at screening.
Exclusion criteria
1. Has a diagnosis of acute promyelocytic leukemia. 2. Has a malignancy that is known to contain a non-synonymous mutation, insertion, or deletion in the TP53 gene determined previously or at screening. 3. Has presence of central nervous system (CNS) involvement of leukemia or a history of primary CNS leukemia. 4. Has a second concurrent primary malignancy that required active treatment within the previous 2 years, except for localized cancers that have apparently been cured, such as non-melanoma skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast. 5. Has any condition that would preclude adequate absorption of DS-3032b, including refractory nausea and vomiting, malabsorption, biliary shunt, significant bowel resection, and/or graft-versus-host disease (GVHD) affecting the gut. 6. Has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals, known human immunodeficiency virus infection, or active hepatitis B or C infection. 7. Has a concomitant medical condition that would increase the risk of toxicity. 8. Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE Grade ≤ 1, or baseline. Subjects with chronic Grade 2 toxicities may be eligible at the discretion of the Investigator and Sponsor (eg, Grade 2 chemotherapy-induced neuropathy). 9. Has received Hematopoietic Stem Cell Transplantation (HSCT) within 60 days of the first dose of study drugs or has clinically significant GVHD or GVHD requiring initiation of systemic treatment or systemic treatment escalation within 21 days prior to Screening and/or \>Grade 1 persistent or clinically significant GVHD or other non-hematologic toxicity related to HCT. 10. Is receiving concomitant treatment with a strong inhibitor or inducer of cytochrome P450 3A4/5. 11. Has received any therapies intended to treat malignancy within 7 days (small molecules) or 21 days (anti-body/immune based biologics) of first receipt of study drugs \[except for hydroxyurea, which must be discontinued at least 48 hours (Day -2) prior to study treatment\]. 12. Had major surgery within 4 weeks prior to study drug treatment. 13. Participated in a therapeutic clinical study within a washout time of 2 weeks or 5 half-lives of the drug/biologic (whichever is longer) before starting study drug treatment under this protocol, or current participation in other therapeutic investigational procedures. 14. Has prolongation of corrected QT interval using Fridericia's method (QTcF) at rest, where the mean QTcF interval is \> 480 ms based on triplicate electrocardiograms (ECGs). 15. Is pregnant or breastfeeding. 16. Has substance abuse or medical, psychological, or social conditions that, in the opinion of the Investigator, may interfere with the subject's participation in the clinical study or evaluation of the clinical study results. 17. Prior treatment with an MDM2 inhibitor.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | From the date the participant signed the informed consent form up to 5 years of first participant enrolled | A DLT was defined as any treatment-emergent adverse event not attributable to disease or disease-related processes occurring during the observation period (Cycle 1) in each dose-level cohort and is Grade (Gr) 3 or higher according to NCI CTCAE Version 5.0 (Version 4.03 before 01 Apr 2018), with these exceptions: for elevations in hepatic function enzymes, a DLT is defined as: Gr ≥3 aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels lasting \>3 days; AST/ALT \>5 × ULN if accompanied by ≥Gr 2 elevation in bilirubin. Potential DLTs include: Participants who are unable to complete at least 75% of milademetan or AZA in Cycle 1 as a result of non-disease-related Gr ≥2 events; Persistent bone marrow aplasia in the absence of malignant cell infiltration, and failure to recover a peripheral absolute neutrophil count ≥0.5 × 10\^9/L and platelets ≥20 × 10\^9/L while withholding study drug, resulting in \>2-week delay in initiating Cycle 2. |
| Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | From the date the participant signed the informed consent form up to 30 days after the last dose in the last participant, up to approximately 6 years of first participant enrolled | A treatment-emergent adverse event (TEAE) is defined as an adverse event that emerges during the treatment period (up to 30 days after last dose), having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pre-treatment state, when the adverse event is continuous. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Maximum Concentration (Tmax) Following Administration of Milademetan Alone | Predose, 1 hour (hr), 2 hr, 3 hr, 6 hr, 8 hr, 10 hr of Cycle 1, Day 1 (Cohorts 1-9d) and Cycle 1, Day 15 (Cohorts 1-5 and 7c) (each cycle is 28 days) | Pharmacokinetic parameter time to maximum concentration (Tmax) of milademetan was assessed at select time points. |
| Time to Maximum Concentration (Tmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Predose, 0.5 hour (hr), 1 hr, 2 hr, 3 hr, 6 hr of Cycle 1, Day 1 (AZA); Predose, 0.5 hr, 1 hr, 2 hr, 3 hr, 4 hr, 6-10 hr of Day 5, Day 7 (predose) (Cohorts 10e and 12e), Day 8 (Cohorts 11f and 13f), and Day 14 (Cohorts 10e-13f) (each cycle is 28 days) | Pharmacokinetic parameter time to maximum concentration (Tmax) was assessed at select time points. |
| Trough Plasma Concentration (Ctrough) Following Administration of Milademetan Alone | Predose, 1 hour (hr), 2 hr, 3 hr, 6 hr, 8 hr, 10 hr of Cycle 1, Day 15 (Cohorts 1-5 and 7c) (each cycle is 28 days) | Pharmacokinetic parameter plasma concentration before next dose (Ctrough) of milademetan was assessed at Cycle 1, Day 15 and the geometric means (coefficient of variation %) are presented. |
| Maximum Plasma Concentration (Cmax) Following Administration of Milademetan Alone | Predose, 1 hour (hr), 2 hr, 3 hr, 6 hr, 8 hr, 10 hr of Cycle 1, Day 1 (Cohorts 1-9d) and Cycle 1, Day 15 (Cohorts 1-5 and 7c) (each cycle is 28 days) | Pharmacokinetic parameter maximum plasma concentration (Cmax) of milademetan was assessed at select time points and the geometric means (coefficient of variation %) are presented. |
| Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Predose, 0.5 hr, 1 hr, 2 hr, 3 hr, 4 hr, 6-10 hr of Cycle 1, Day 5 (Cohorts 10e and 12e) and Predose of Cycle 1, Day 14 (Cohorts 10e, 11f, and 12e) (each cycle is 28 days) | Pharmacokinetic parameter area under the plasma concentration curve up to 24 hours (AUC0-24) was assessed at select time points and the geometric means (coefficient of variation %) are presented. |
| Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 1 (6 hours postdose) up to Day 21-22 (predose), up to approximately 6 years of first participant enrolled | Pharmacodynamic biomarker serum macrophage inhibitory cytokine-1 (MIC-1) concentrations of milademetan were assessed for Cohorts 1 though 9d. Fold change is the ratio of post-baseline MIC-1 values with respect to the baseline values and is the measure of change of MIC-1 from baseline. |
| Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Day 5 (predose) up to Day 22 (predose), up to approximately 6 years of first participant enrolled | Pharmacodynamic biomarker serum macrophage inhibitory cytokine-1 (MIC-1) concentrations were assessed for Cohorts 10e though 13f. Fold change is the ratio of post-baseline MIC-1 values with respect to the baseline values and is the measure of change of MIC-1 from baseline. |
| Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan Alone | Predose, 1 hour (hr), 2 hr, 3 hr, 6 hr, 8 hr, 10 hr of Cycle 1, Day 1 (Cohorts 1-9d) and Cycle 1, Day 15 (Cohorts 1-5 and 7c) (each cycle is 28 days) | Pharmacokinetic parameter area under the plasma concentration curve up to 24 hours (AUC0-24) of milademetan was assessed at select time points and the geometric means (coefficient of variation %) are presented. |
| Maximum Plasma Concentration (Cmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Predose, 0.5 hour (hr), 1 hr, 2 hr, 3 hr, 6 hr of Cycle 1, Day 1 (AZA); Predose, 0.5 hr, 1 hr, 2 hr, 3 hr, 4 hr, 6-10 hr of Day 5, Day 7 (predose) (Cohorts 10e and 12e), Day 8 (Cohorts 11f and 13f), and Day 14 (Cohorts 10e-13f) (each cycle is 28 days) | Pharmacokinetic parameter maximum plasma concentration (Cmax) was assessed at select time points and the geometric means (coefficient of variation %) are presented. |
Countries
United States
Participant flow
Recruitment details
A total of 74 participants who met all inclusion criteria and no exclusion criteria were enrolled and treated at 5 clinic sites in the United States.
Pre-assignment details
Dose escalation of milademetan was used to determine the maximum tolerated dose. A starting dose of 60 mg milademetan was based on safety and tolerability data obtained in the solid tumor or lymphoma first-in-human study of milademetan (Study DS3032-A-U101; NCT01877382).
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Milademetan 60 mg Participants were administered 60 mg milademetan daily as oral capsules on Days 1 to 21 of a 28-day cycle. | 7 |
| Cohort 2: Milademetan 90 mg Participants were administered 90 mg milademetan daily as oral capsules on Days 1 to 21 of a 28-day cycle. | 6 |
| Cohort 3: Milademetan 120 mg Participants were administered 120 mg milademetan daily as oral capsules on Days 1 to 21 of a 28-day cycle. | 11 |
| Cohort 4: Milademetan 160 mg Participants were administered 160 mg milademetan daily as oral capsules on Days 1 to 21 of a 28-day cycle. | 8 |
| Cohort 5: Milademetan 210 mg Participants were administered 210 mg milademetan daily as oral capsules on Days 1 to 21 of a 28-day cycle | 5 |
| Cohort 6b: Milademetan 160 mg Participants were administered 160 mg milademetan daily as oral capsules on Days 1 to 7 of a 28-day cycle. | 7 |
| Cohort 7c: Milademetan 160 mg Participants were administered 160 mg milademetan daily as oral capsules for 3 of 14 days repeated twice in a 28-day cycle. | 3 |
| Cohort 8d: Milademetan 160 mg Participants were administered 160 mg milademetan daily as oral capsules on Days 1 to 14 of a 28-day cycle. | 6 |
| Cohort 9d: Milademetan 220 mg Participants were administered 220 mg milademetan daily as oral capsules on Days 1 to 14 of a 28-day cycle. | 4 |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 Participants were administered 160 mg milademetan daily as oral capsules on Days 5 to 14 of a 28-day cycle and azacitidine was administered on Days 1 to 7. | 9 |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 Participants were administered 160 mg milademetan daily as oral capsules on Days 8 to 14 of a 28-day cycle and azacitidine was administered on Days 1 to 7. | 3 |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 Participants were administered 200 mg milademetan daily as oral capsules on Days 5 to 14 of a 28-day cycle and azacitidine was administered on Days 1 to 7. | 4 |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 Participants were administered 200 mg milademetan daily as oral capsules on Days 8 to 14 of a 28-day cycle and azacitidine was administered on Days 1 to 7. | 1 |
| Total | 74 |
Baseline characteristics
| Characteristic | Cohort 2: Milademetan 90 mg | Cohort 3: Milademetan 120 mg | Cohort 5: Milademetan 210 mg | Cohort 6b: Milademetan 160 mg | Cohort 7c: Milademetan 160 mg | Cohort 8d: Milademetan 160 mg | Cohort 9d: Milademetan 220 mg | Cohort 4: Milademetan 160 mg | Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Cohort 1: Milademetan 60 mg | Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 63.8 years STANDARD_DEVIATION 10.6 | 61.8 years STANDARD_DEVIATION 15.6 | 69.2 years STANDARD_DEVIATION 7.2 | 71.3 years STANDARD_DEVIATION 6.4 | 66.7 years STANDARD_DEVIATION 7.6 | 61.8 years STANDARD_DEVIATION 20.1 | 72.0 years STANDARD_DEVIATION 8.2 | 70.4 years STANDARD_DEVIATION 6.1 | 60.3 years STANDARD_DEVIATION 19.8 | 49.3 years STANDARD_DEVIATION 25.4 | 70.8 years STANDARD_DEVIATION 7.1 | 67.0 years STANDARD_DEVIATION 14.7 | 60.0 years | 66.6 years STANDARD_DEVIATION 12.1 |
| Age, Customized ≤65 years | 4 Participants | 5 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 2 Participants | 5 Participants | 2 Participants | 1 Participants | 4 Participants | 1 Participants | 31 Participants |
| Age, Customized >65 years | 2 Participants | 6 Participants | 4 Participants | 6 Participants | 2 Participants | 3 Participants | 3 Participants | 6 Participants | 4 Participants | 1 Participants | 3 Participants | 3 Participants | 0 Participants | 43 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 9 Participants | 4 Participants | 6 Participants | 1 Participants | 4 Participants | 4 Participants | 6 Participants | 8 Participants | 1 Participants | 4 Participants | 6 Participants | 1 Participants | 60 Participants |
| Region of Enrollment United States | 6 participants | 11 participants | 5 participants | 7 participants | 3 participants | 6 participants | 4 participants | 8 participants | 9 participants | 3 participants | 4 participants | 7 participants | 1 participants | 74 participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 3 Participants | 3 Participants | 6 Participants | 1 Participants | 1 Participants | 4 Participants | 1 Participants | 29 Participants |
| Sex: Female, Male Male | 4 Participants | 8 Participants | 4 Participants | 5 Participants | 2 Participants | 5 Participants | 1 Participants | 5 Participants | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 0 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 7 | 0 / 6 | 1 / 11 | 1 / 8 | 1 / 5 | 1 / 7 | 1 / 3 | 1 / 6 | 2 / 4 | 2 / 9 | 2 / 3 | 1 / 4 | 0 / 1 |
| other Total, other adverse events | 7 / 7 | 6 / 6 | 11 / 11 | 8 / 8 | 5 / 5 | 7 / 7 | 3 / 3 | 6 / 6 | 4 / 4 | 9 / 9 | 3 / 3 | 4 / 4 | 1 / 1 |
| serious Total, serious adverse events | 4 / 7 | 5 / 6 | 9 / 11 | 5 / 8 | 5 / 5 | 4 / 7 | 2 / 3 | 3 / 6 | 2 / 4 | 9 / 9 | 3 / 3 | 4 / 4 | 0 / 1 |
Outcome results
Primary
Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA)
A treatment-emergent adverse event (TEAE) is defined as an adverse event that emerges during the treatment period (up to 30 days after last dose), having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pre-treatment state, when the adverse event is continuous.
Time frame: From the date the participant signed the informed consent form up to 30 days after the last dose in the last participant, up to approximately 6 years of first participant enrolled
Population: Safety events were assessed in the Safety Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypokalaemia | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Device-related infection | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Athralgia | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Any TEAEs | 7 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypotension | 2 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Escherichia infection | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Depression | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dyspnoea | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pancytopenia | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Nausea | 5 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Muscular weakness | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Asthenia | 1 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Constipation | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypophosphataemia | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hemorrhoids | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pneumonia fungal | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Alanine aminotransferase increased | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Oedema peripheral | 1 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pneumonia | 3 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Headache | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Diarrhoea | 2 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Oropharyngeal pain | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Abdominal pain | 2 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Malaise | 1 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Febrile neutropenia | 1 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Contusion | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dehydration | 1 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fluid overload | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Rhinorrhoea | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Vomiting | 2 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dizziness | 1 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Insomnia | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Anaemia | 2 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypomagnesaemia | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hyponatraemia | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fatigue | 2 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Death | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pyrexia | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Myalgia | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Lung infection | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hyperuricaemia | 2 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Sepsis | 2 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Rash maculo-papular | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Epistaxis | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Neutropenia | 1 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Thrombocytopenia | 2 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Decreased appetite | 2 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Cough | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dehydration | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Muscular weakness | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Epistaxis | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hyponatraemia | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Oedema peripheral | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypokalaemia | 1 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypophosphataemia | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hyperuricaemia | 1 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Headache | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Anaemia | 3 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Febrile neutropenia | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Decreased appetite | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Depression | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Asthenia | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pancytopenia | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Insomnia | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Abdominal pain | 1 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Malaise | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pneumonia fungal | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Death | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Device-related infection | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Sepsis | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pyrexia | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Athralgia | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Cough | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dyspnoea | 1 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Any TEAEs | 6 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hemorrhoids | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pneumonia | 1 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Constipation | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Alanine aminotransferase increased | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dizziness | 1 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Nausea | 4 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypotension | 2 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Diarrhoea | 2 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Rhinorrhoea | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Contusion | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fluid overload | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypomagnesaemia | 1 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Vomiting | 1 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Escherichia infection | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Neutropenia | 2 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Myalgia | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Oropharyngeal pain | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Rash maculo-papular | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fatigue | 1 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Thrombocytopenia | 1 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Lung infection | 1 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hyponatraemia | 0 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Escherichia infection | 0 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hemorrhoids | 0 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fluid overload | 0 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Asthenia | 1 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hyperuricaemia | 0 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Abdominal pain | 0 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Malaise | 1 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dizziness | 0 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Sepsis | 1 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Cough | 0 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dyspnoea | 2 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pneumonia | 1 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Constipation | 0 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypotension | 2 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Contusion | 0 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypomagnesaemia | 3 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Neutropenia | 2 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Myalgia | 0 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Lung infection | 2 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Epistaxis | 0 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypokalaemia | 1 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Decreased appetite | 2 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Headache | 0 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Anaemia | 3 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypophosphataemia | 0 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Febrile neutropenia | 3 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Oedema peripheral | 4 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Muscular weakness | 0 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Thrombocytopenia | 4 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fatigue | 5 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Rash maculo-papular | 0 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Vomiting | 4 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Rhinorrhoea | 0 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Diarrhoea | 8 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Nausea | 8 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Alanine aminotransferase increased | 0 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Any TEAEs | 11 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Athralgia | 0 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pyrexia | 0 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pneumonia fungal | 0 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Death | 0 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dehydration | 1 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pancytopenia | 0 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Depression | 0 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Oropharyngeal pain | 0 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Device-related infection | 0 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Insomnia | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Asthenia | 1 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Lung infection | 2 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fatigue | 5 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Myalgia | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Oropharyngeal pain | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Rash maculo-papular | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Neutropenia | 3 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Vomiting | 4 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Escherichia infection | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Diarrhoea | 5 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Contusion | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypomagnesaemia | 1 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fluid overload | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Rhinorrhoea | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypotension | 1 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Nausea | 6 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Constipation | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Insomnia | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Alanine aminotransferase increased | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pneumonia | 3 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Any TEAEs | 8 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hemorrhoids | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Cough | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dyspnoea | 1 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Athralgia | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dehydration | 1 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pyrexia | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Sepsis | 1 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pneumonia fungal | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Device-related infection | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Death | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Malaise | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Abdominal pain | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pancytopenia | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hyponatraemia | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dizziness | 2 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Anaemia | 3 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Headache | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Decreased appetite | 3 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hyperuricaemia | 1 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypophosphataemia | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Oedema peripheral | 2 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Depression | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypokalaemia | 4 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Thrombocytopenia | 5 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Epistaxis | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Muscular weakness | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Febrile neutropenia | 1 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hemorrhoids | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Anaemia | 1 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Lung infection | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fatigue | 3 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Athralgia | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Oropharyngeal pain | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dehydration | 1 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Myalgia | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Depression | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hyperuricaemia | 2 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hyponatraemia | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Rash maculo-papular | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dyspnoea | 3 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Vomiting | 3 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Headache | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pneumonia fungal | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Neutropenia | 1 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Contusion | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Diarrhoea | 3 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Muscular weakness | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypokalaemia | 3 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Sepsis | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Malaise | 1 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Device-related infection | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Rhinorrhoea | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Febrile neutropenia | 1 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fluid overload | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypomagnesaemia | 2 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Decreased appetite | 3 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Nausea | 4 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Death | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Insomnia | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypotension | 1 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Constipation | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Asthenia | 2 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Epistaxis | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Thrombocytopenia | 1 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Alanine aminotransferase increased | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dizziness | 2 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pancytopenia | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Any TEAEs | 5 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypophosphataemia | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Escherichia infection | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pneumonia | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Cough | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pyrexia | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Abdominal pain | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Oedema peripheral | 1 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Rash maculo-papular | 0 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Febrile neutropenia | 0 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hyperuricaemia | 0 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Malaise | 1 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Cough | 0 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Constipation | 0 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Contusion | 0 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Myalgia | 0 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Epistaxis | 0 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Headache | 0 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypophosphataemia | 0 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Muscular weakness | 0 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Rhinorrhoea | 0 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Alanine aminotransferase increased | 0 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Athralgia | 0 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Death | 0 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Depression | 0 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Device-related infection | 0 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Escherichia infection | 0 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fluid overload | 0 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hemorrhoids | 0 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hyponatraemia | 0 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Insomnia | 0 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Oropharyngeal pain | 0 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pancytopenia | 0 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pneumonia fungal | 0 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pyrexia | 0 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Any TEAEs | 7 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Nausea | 3 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Diarrhoea | 4 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Vomiting | 2 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fatigue | 2 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Thrombocytopenia | 1 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Oedema peripheral | 3 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Anaemia | 1 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Decreased appetite | 2 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypokalaemia | 2 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Lung infection | 2 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Neutropenia | 0 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypomagnesaemia | 2 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypotension | 0 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pneumonia | 0 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dyspnoea | 1 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Sepsis | 1 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Abdominal pain | 2 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Asthenia | 1 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dehydration | 1 Participants |
| Cohort 6b: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dizziness | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Nausea | 2 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Febrile neutropenia | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Alanine aminotransferase increased | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pneumonia fungal | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hyponatraemia | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Any TEAEs | 3 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pyrexia | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Athralgia | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Device-related infection | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Abdominal pain | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dizziness | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Sepsis | 1 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Insomnia | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Escherichia infection | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Malaise | 1 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dyspnoea | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Cough | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pneumonia | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Constipation | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypotension | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypomagnesaemia | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Contusion | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hemorrhoids | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Depression | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Neutropenia | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Oropharyngeal pain | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fluid overload | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Myalgia | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Lung infection | 1 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypokalaemia | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Epistaxis | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Decreased appetite | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Headache | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Anaemia | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Oedema peripheral | 1 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypophosphataemia | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Thrombocytopenia | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Muscular weakness | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pancytopenia | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Asthenia | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fatigue | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dehydration | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Vomiting | 2 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Rash maculo-papular | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Diarrhoea | 2 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hyperuricaemia | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Death | 0 Participants |
| Cohort 7c: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Rhinorrhoea | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hyponatraemia | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Device-related infection | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Insomnia | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Depression | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Oropharyngeal pain | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pancytopenia | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Death | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pneumonia fungal | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Athralgia | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pyrexia | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Alanine aminotransferase increased | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Febrile neutropenia | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Any TEAEs | 6 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Nausea | 4 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Rhinorrhoea | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Diarrhoea | 3 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Rash maculo-papular | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Vomiting | 3 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fatigue | 1 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Muscular weakness | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dehydration | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Thrombocytopenia | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypophosphataemia | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Oedema peripheral | 1 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Anaemia | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Headache | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Decreased appetite | 1 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Epistaxis | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypokalaemia | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Myalgia | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Lung infection | 1 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Neutropenia | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Contusion | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypomagnesaemia | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Constipation | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypotension | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pneumonia | 1 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Cough | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dyspnoea | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Malaise | 1 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Sepsis | 1 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Abdominal pain | 2 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hyperuricaemia | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dizziness | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Asthenia | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fluid overload | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Escherichia infection | 0 Participants |
| Cohort 8d: Milademetan 160 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hemorrhoids | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Asthenia | 1 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Depression | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypokalaemia | 1 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dizziness | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Contusion | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Device-related infection | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Myalgia | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Neutropenia | 1 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Lung infection | 2 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Vomiting | 3 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Escherichia infection | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Oropharyngeal pain | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pyrexia | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Febrile neutropenia | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Athralgia | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pancytopenia | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fatigue | 1 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Abdominal pain | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Muscular weakness | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hyperuricaemia | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Sepsis | 1 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Death | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Thrombocytopenia | 1 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Any TEAEs | 4 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Insomnia | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Malaise | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Diarrhoea | 3 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypophosphataemia | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dehydration | 1 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fluid overload | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Oedema peripheral | 1 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Rhinorrhoea | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dyspnoea | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pneumonia fungal | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Headache | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Anaemia | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Alanine aminotransferase increased | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Cough | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pneumonia | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hemorrhoids | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Rash maculo-papular | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypotension | 1 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Decreased appetite | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Nausea | 3 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hyponatraemia | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Constipation | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Epistaxis | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypomagnesaemia | 0 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Cough | 4 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Depression | 1 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Alanine aminotransferase increased | 1 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Thrombocytopenia | 0 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dehydration | 2 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypokalaemia | 1 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hemorrhoids | 2 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Asthenia | 0 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fluid overload | 1 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Neutropenia | 1 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Rash maculo-papular | 0 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Myalgia | 3 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypophosphataemia | 2 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pyrexia | 1 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Anaemia | 0 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Oropharyngeal pain | 2 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Escherichia infection | 2 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Device-related infection | 2 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Lung infection | 3 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Death | 0 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Decreased appetite | 3 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Contusion | 2 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Diarrhoea | 1 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Vomiting | 3 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Rhinorrhoea | 1 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypotension | 3 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pneumonia fungal | 0 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypomagnesaemia | 0 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pneumonia | 3 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Abdominal pain | 3 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Oedema peripheral | 1 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Muscular weakness | 2 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pancytopenia | 2 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Nausea | 5 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Athralgia | 1 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Malaise | 0 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fatigue | 3 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Febrile neutropenia | 0 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dyspnoea | 3 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hyponatraemia | 0 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Constipation | 2 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Insomnia | 1 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hyperuricaemia | 0 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Sepsis | 2 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Epistaxis | 2 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Any TEAEs | 9 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Headache | 2 Participants |
| Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dizziness | 2 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Muscular weakness | 1 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Diarrhoea | 2 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Rash maculo-papular | 0 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Febrile neutropenia | 0 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pancytopenia | 0 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Vomiting | 2 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fatigue | 2 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Device-related infection | 0 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Thrombocytopenia | 0 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypophosphataemia | 1 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Death | 2 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Oedema peripheral | 1 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Headache | 1 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Anaemia | 0 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fluid overload | 1 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Epistaxis | 0 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dehydration | 0 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Decreased appetite | 2 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Oropharyngeal pain | 0 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypokalaemia | 0 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Myalgia | 1 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Escherichia infection | 0 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Lung infection | 3 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Contusion | 2 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Neutropenia | 0 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dizziness | 1 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Constipation | 2 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hyponatraemia | 1 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Depression | 0 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypotension | 1 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Cough | 3 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pneumonia | 1 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Insomnia | 1 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypomagnesaemia | 0 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hemorrhoids | 0 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dyspnoea | 3 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Malaise | 0 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Asthenia | 0 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Sepsis | 0 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hyperuricaemia | 0 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pneumonia fungal | 1 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Abdominal pain | 1 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pyrexia | 1 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Alanine aminotransferase increased | 1 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Any TEAEs | 3 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Rhinorrhoea | 2 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Athralgia | 1 Participants |
| Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Nausea | 2 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hyperuricaemia | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Malaise | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypomagnesaemia | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Headache | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Depression | 1 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Any TEAEs | 4 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Insomnia | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fatigue | 2 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pneumonia fungal | 1 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fluid overload | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Decreased appetite | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dyspnoea | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Muscular weakness | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Rash maculo-papular | 3 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Diarrhoea | 1 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Febrile neutropenia | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Oedema peripheral | 1 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Nausea | 2 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Vomiting | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Device-related infection | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Athralgia | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pyrexia | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pneumonia | 1 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hemorrhoids | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Contusion | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Alanine aminotransferase increased | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Thrombocytopenia | 3 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dizziness | 1 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Asthenia | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Lung infection | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hyponatraemia | 1 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Myalgia | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Cough | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Neutropenia | 1 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Anaemia | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypophosphataemia | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypokalaemia | 1 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Escherichia infection | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Death | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Constipation | 1 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pancytopenia | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dehydration | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Rhinorrhoea | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Oropharyngeal pain | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Sepsis | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypotension | 1 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Epistaxis | 1 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Abdominal pain | 1 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypokalaemia | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Abdominal pain | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Oropharyngeal pain | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypotension | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Insomnia | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Cough | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Device-related infection | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Epistaxis | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Death | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Anaemia | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pneumonia | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pancytopenia | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Malaise | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Athralgia | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Headache | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Oedema peripheral | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Any TEAEs | 1 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dyspnoea | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dizziness | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Thrombocytopenia | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Rhinorrhoea | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hemorrhoids | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypophosphataemia | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Sepsis | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hyperuricaemia | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Febrile neutropenia | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Asthenia | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Escherichia infection | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Depression | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fatigue | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pneumonia fungal | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hyponatraemia | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Nausea | 1 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Alanine aminotransferase increased | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Muscular weakness | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Vomiting | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Pyrexia | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Contusion | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Lung infection | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Dehydration | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Rash maculo-papular | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Neutropenia | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypomagnesaemia | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Constipation | 1 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Myalgia | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Diarrhoea | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fluid overload | 0 Participants |
| Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Decreased appetite | 0 Participants |
Primary
Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA)
A DLT was defined as any treatment-emergent adverse event not attributable to disease or disease-related processes occurring during the observation period (Cycle 1) in each dose-level cohort and is Grade (Gr) 3 or higher according to NCI CTCAE Version 5.0 (Version 4.03 before 01 Apr 2018), with these exceptions: for elevations in hepatic function enzymes, a DLT is defined as: Gr ≥3 aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels lasting \>3 days; AST/ALT \>5 × ULN if accompanied by ≥Gr 2 elevation in bilirubin. Potential DLTs include: Participants who are unable to complete at least 75% of milademetan or AZA in Cycle 1 as a result of non-disease-related Gr ≥2 events; Persistent bone marrow aplasia in the absence of malignant cell infiltration, and failure to recover a peripheral absolute neutrophil count ≥0.5 × 10\^9/L and platelets ≥20 × 10\^9/L while withholding study drug, resulting in \>2-week delay in initiating Cycle 2.
Time frame: From the date the participant signed the informed consent form up to 5 years of first participant enrolled
Population: Dose-limiting toxicities were reported in the DLT evaluable set for Cohorts 1, 4, 5, and 9d of Part 1 and Cohort 12e of Part 1a.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Milademetan 60 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Cellulitis | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Renal failure | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fatigue | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Nausea | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Syncope | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Vomiting | 1 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypokalaemia | 0 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Participants with TEAEs classified as DLTs | 1 Participants |
| Cohort 1: Milademetan 60 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Diarrhoea | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Vomiting | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Syncope | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Participants with TEAEs classified as DLTs | 2 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fatigue | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Cellulitis | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Diarrhoea | 1 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypokalaemia | 1 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Renal failure | 0 Participants |
| Cohort 4: Milademetan 160 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Nausea | 0 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Cellulitis | 1 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Renal failure | 1 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Diarrhoea | 0 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Syncope | 0 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypokalaemia | 0 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Nausea | 1 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fatigue | 1 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Participants with TEAEs classified as DLTs | 3 Participants |
| Cohort 5: Milademetan 210 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Vomiting | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Nausea | 2 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Participants with TEAEs classified as DLTs | 2 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fatigue | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypokalaemia | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Cellulitis | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Diarrhoea | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Syncope | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Vomiting | 0 Participants |
| Cohort 9d: Milademetan 220 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Renal failure | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Syncope | 1 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Participants with TEAEs classified as DLTs | 2 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Nausea | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Fatigue | 2 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Cellulitis | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Diarrhoea | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Hypokalaemia | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Renal failure | 0 Participants |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) | Vomiting | 0 Participants |
Secondary
Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan Alone
Pharmacokinetic parameter area under the plasma concentration curve up to 24 hours (AUC0-24) of milademetan was assessed at select time points and the geometric means (coefficient of variation %) are presented.
Time frame: Predose, 1 hour (hr), 2 hr, 3 hr, 6 hr, 8 hr, 10 hr of Cycle 1, Day 1 (Cohorts 1-9d) and Cycle 1, Day 15 (Cohorts 1-5 and 7c) (each cycle is 28 days)
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Milademetan 60 mg | Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan Alone | Cycle 1, Day 1 | 4646.7 ng*h/mL | Geometric Coefficient of Variation 47.7 |
| Cohort 1: Milademetan 60 mg | Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan Alone | Cycle 1, Day 15 | 7244.6 ng*h/mL | Geometric Coefficient of Variation 28.9 |
| Cohort 4: Milademetan 160 mg | Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan Alone | Cycle 1, Day 1 | 4478.1 ng*h/mL | Geometric Coefficient of Variation 31.2 |
| Cohort 4: Milademetan 160 mg | Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan Alone | Cycle 1, Day 15 | 8392.9 ng*h/mL | Geometric Coefficient of Variation 56.5 |
| Cohort 5: Milademetan 210 mg | Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan Alone | Cycle 1, Day 1 | 6585.4 ng*h/mL | Geometric Coefficient of Variation 54.8 |
| Cohort 5: Milademetan 210 mg | Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan Alone | Cycle 1, Day 15 | 9854.9 ng*h/mL | Geometric Coefficient of Variation 54.6 |
| Cohort 9d: Milademetan 220 mg | Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan Alone | Cycle 1, Day 1 | 8315.1 ng*h/mL | Geometric Coefficient of Variation 101.2 |
| Cohort 9d: Milademetan 220 mg | Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan Alone | Cycle 1, Day 15 | 10710.8 ng*h/mL | Geometric Coefficient of Variation 54.2 |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan Alone | Cycle 1, Day 1 | 9794.0 ng*h/mL | Geometric Coefficient of Variation 39.4 |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan Alone | Cycle 1, Day 15 | 20330.2 ng*h/mL | Geometric Coefficient of Variation 15.9 |
| Cohort 6b: Milademetan 160 mg | Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan Alone | Cycle 1, Day 15 | NA ng*h/mL | — |
| Cohort 6b: Milademetan 160 mg | Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan Alone | Cycle 1, Day 1 | 7222.5 ng*h/mL | Geometric Coefficient of Variation 43.1 |
| Cohort 7c: Milademetan 160 mg | Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan Alone | Cycle 1, Day 15 | 7714.3 ng*h/mL | Geometric Coefficient of Variation 30.5 |
| Cohort 7c: Milademetan 160 mg | Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan Alone | Cycle 1, Day 1 | 10165.6 ng*h/mL | Geometric Coefficient of Variation 64.6 |
| Cohort 8d: Milademetan 160 mg | Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan Alone | Cycle 1, Day 1 | 8973.9 ng*h/mL | Geometric Coefficient of Variation 28.1 |
| Cohort 8d: Milademetan 160 mg | Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan Alone | Cycle 1, Day 15 | NA ng*h/mL | — |
| Cohort 9d: Milademetan 220 mg | Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan Alone | Cycle 1, Day 1 | 20893.9 ng*h/mL | Geometric Coefficient of Variation 23.2 |
| Cohort 9d: Milademetan 220 mg | Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan Alone | Cycle 1, Day 15 | NA ng*h/mL | — |
Secondary
Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA)
Pharmacokinetic parameter area under the plasma concentration curve up to 24 hours (AUC0-24) was assessed at select time points and the geometric means (coefficient of variation %) are presented.
Time frame: Predose, 0.5 hr, 1 hr, 2 hr, 3 hr, 4 hr, 6-10 hr of Cycle 1, Day 5 (Cohorts 10e and 12e) and Predose of Cycle 1, Day 14 (Cohorts 10e, 11f, and 12e) (each cycle is 28 days)
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Milademetan 60 mg | Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 5 | 8238.7 ng*h/mL | Geometric Coefficient of Variation 43 |
| Cohort 1: Milademetan 60 mg | Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 14 | 22563.8 ng*h/mL | Geometric Coefficient of Variation 52.9 |
| Cohort 4: Milademetan 160 mg | Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 5 | NA ng*h/mL | — |
| Cohort 4: Milademetan 160 mg | Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 14 | 15755.5 ng*h/mL | Geometric Coefficient of Variation 29.4 |
| Cohort 5: Milademetan 210 mg | Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 5 | 21299.3 ng*h/mL | Geometric Coefficient of Variation 16.3 |
| Cohort 5: Milademetan 210 mg | Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 14 | 19967.5 ng*h/mL | Geometric Coefficient of Variation 18.5 |
Secondary
Maximum Plasma Concentration (Cmax) Following Administration of Milademetan Alone
Pharmacokinetic parameter maximum plasma concentration (Cmax) of milademetan was assessed at select time points and the geometric means (coefficient of variation %) are presented.
Time frame: Predose, 1 hour (hr), 2 hr, 3 hr, 6 hr, 8 hr, 10 hr of Cycle 1, Day 1 (Cohorts 1-9d) and Cycle 1, Day 15 (Cohorts 1-5 and 7c) (each cycle is 28 days)
Population: Pharmacokinetics were assessed in the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Milademetan 60 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan Alone | Cycle 1, Day 1 | 386.0 ng/mL | Geometric Coefficient of Variation 42.2 |
| Cohort 1: Milademetan 60 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan Alone | Cycle 1, Day 15 | 498.5 ng/mL | Geometric Coefficient of Variation 40.3 |
| Cohort 4: Milademetan 160 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan Alone | Cycle 1, Day 15 | 562.6 ng/mL | Geometric Coefficient of Variation 58.6 |
| Cohort 4: Milademetan 160 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan Alone | Cycle 1, Day 1 | 342.5 ng/mL | Geometric Coefficient of Variation 23.4 |
| Cohort 5: Milademetan 210 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan Alone | Cycle 1, Day 15 | 614.3 ng/mL | Geometric Coefficient of Variation 55.3 |
| Cohort 5: Milademetan 210 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan Alone | Cycle 1, Day 1 | 505.9 ng/mL | Geometric Coefficient of Variation 56.8 |
| Cohort 9d: Milademetan 220 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan Alone | Cycle 1, Day 1 | 622.3 ng/mL | Geometric Coefficient of Variation 94.5 |
| Cohort 9d: Milademetan 220 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan Alone | Cycle 1, Day 15 | 753.8 ng/mL | Geometric Coefficient of Variation 79.8 |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan Alone | Cycle 1, Day 1 | 747.9 ng/mL | Geometric Coefficient of Variation 48.1 |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan Alone | Cycle 1, Day 15 | 1329.2 ng/mL | Geometric Coefficient of Variation 21.9 |
| Cohort 6b: Milademetan 160 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan Alone | Cycle 1, Day 15 | NA ng/mL | — |
| Cohort 6b: Milademetan 160 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan Alone | Cycle 1, Day 1 | 440.0 ng/mL | Geometric Coefficient of Variation 74.7 |
| Cohort 7c: Milademetan 160 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan Alone | Cycle 1, Day 1 | 758.1 ng/mL | Geometric Coefficient of Variation 44.8 |
| Cohort 7c: Milademetan 160 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan Alone | Cycle 1, Day 15 | 669.2 ng/mL | Geometric Coefficient of Variation 46 |
| Cohort 8d: Milademetan 160 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan Alone | Cycle 1, Day 1 | 657.0 ng/mL | Geometric Coefficient of Variation 27.2 |
| Cohort 8d: Milademetan 160 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan Alone | Cycle 1, Day 15 | NA ng/mL | — |
| Cohort 9d: Milademetan 220 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan Alone | Cycle 1, Day 15 | NA ng/mL | — |
| Cohort 9d: Milademetan 220 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan Alone | Cycle 1, Day 1 | 1607.4 ng/mL | Geometric Coefficient of Variation 34.4 |
Secondary
Maximum Plasma Concentration (Cmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA)
Pharmacokinetic parameter maximum plasma concentration (Cmax) was assessed at select time points and the geometric means (coefficient of variation %) are presented.
Time frame: Predose, 0.5 hour (hr), 1 hr, 2 hr, 3 hr, 6 hr of Cycle 1, Day 1 (AZA); Predose, 0.5 hr, 1 hr, 2 hr, 3 hr, 4 hr, 6-10 hr of Day 5, Day 7 (predose) (Cohorts 10e and 12e), Day 8 (Cohorts 11f and 13f), and Day 14 (Cohorts 10e-13f) (each cycle is 28 days)
Population: Pharmacokinetics were assessed in the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Milademetan 60 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 7 | 702.5 ng/mL | Geometric Coefficient of Variation 46.4 |
| Cohort 1: Milademetan 60 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 8 | NA ng/mL | — |
| Cohort 1: Milademetan 60 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 1 | 527.0 ng/mL | Geometric Coefficient of Variation 61.9 |
| Cohort 1: Milademetan 60 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 5 | 704.8 ng/mL | Geometric Coefficient of Variation 57.6 |
| Cohort 1: Milademetan 60 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 14 | 1488.6 ng/mL | Geometric Coefficient of Variation 55.2 |
| Cohort 4: Milademetan 160 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 7 | NA ng/mL | — |
| Cohort 4: Milademetan 160 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 8 | 327.5 ng/mL | Geometric Coefficient of Variation 51.2 |
| Cohort 4: Milademetan 160 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 5 | NA ng/mL | — |
| Cohort 4: Milademetan 160 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 1 | NA ng/mL | — |
| Cohort 4: Milademetan 160 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 14 | 1057.9 ng/mL | Geometric Coefficient of Variation 20.4 |
| Cohort 5: Milademetan 210 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 7 | 769.8 ng/mL | Geometric Coefficient of Variation 46.7 |
| Cohort 5: Milademetan 210 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 1 | 707.0 ng/mL | Geometric Coefficient of Variation 37.7 |
| Cohort 5: Milademetan 210 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 5 | 1019.6 ng/mL | Geometric Coefficient of Variation 72.2 |
| Cohort 5: Milademetan 210 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 8 | NA ng/mL | — |
| Cohort 5: Milademetan 210 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 14 | 1448.2 ng/mL | Geometric Coefficient of Variation 57.2 |
| Cohort 9d: Milademetan 220 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 8 | 266.0 ng/mL | — |
| Cohort 9d: Milademetan 220 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 5 | NA ng/mL | — |
| Cohort 9d: Milademetan 220 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 1 | NA ng/mL | — |
| Cohort 9d: Milademetan 220 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 7 | NA ng/mL | — |
| Cohort 9d: Milademetan 220 mg | Maximum Plasma Concentration (Cmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 14 | 1190.0 ng/mL | — |
Secondary
Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone
Pharmacodynamic biomarker serum macrophage inhibitory cytokine-1 (MIC-1) concentrations of milademetan were assessed for Cohorts 1 though 9d. Fold change is the ratio of post-baseline MIC-1 values with respect to the baseline values and is the measure of change of MIC-1 from baseline.
Time frame: Day 1 (6 hours postdose) up to Day 21-22 (predose), up to approximately 6 years of first participant enrolled
Population: Pharmacodynamic biomarker, MIC-1, was assessed in the Safety Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Milademetan 60 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 2 (predose) | 2.53 fold change | Standard Deviation 0.83 |
| Cohort 1: Milademetan 60 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 21-22 (predose) | 3.49 fold change | Standard Deviation 1.88 |
| Cohort 1: Milademetan 60 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 1 (6 hours postdose) | 3.14 fold change | Standard Deviation 1.23 |
| Cohort 1: Milademetan 60 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 15 (predose) | 2.88 fold change | Standard Deviation 0.64 |
| Cohort 1: Milademetan 60 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 8 (predose) | 4.13 fold change | Standard Deviation 2.46 |
| Cohort 4: Milademetan 160 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 8 (predose) | 6.35 fold change | Standard Deviation 4.61 |
| Cohort 4: Milademetan 160 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 1 (6 hours postdose) | 2.78 fold change | Standard Deviation 0.95 |
| Cohort 4: Milademetan 160 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 21-22 (predose) | 4.61 fold change | Standard Deviation 2.66 |
| Cohort 4: Milademetan 160 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 2 (predose) | 3.31 fold change | Standard Deviation 1.25 |
| Cohort 4: Milademetan 160 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 15 (predose) | 5.64 fold change | Standard Deviation 4.94 |
| Cohort 5: Milademetan 210 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 15 (predose) | 6.04 fold change | Standard Deviation 3.49 |
| Cohort 5: Milademetan 210 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 8 (predose) | 7.41 fold change | Standard Deviation 7.17 |
| Cohort 5: Milademetan 210 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 1 (6 hours postdose) | 3.36 fold change | Standard Deviation 1.38 |
| Cohort 5: Milademetan 210 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 21-22 (predose) | 4.57 fold change | Standard Deviation 3.53 |
| Cohort 5: Milademetan 210 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 2 (predose) | 3.97 fold change | Standard Deviation 2.71 |
| Cohort 9d: Milademetan 220 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 21-22 (predose) | 6.57 fold change | Standard Deviation 4.22 |
| Cohort 9d: Milademetan 220 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 2 (predose) | 3.44 fold change | Standard Deviation 1.63 |
| Cohort 9d: Milademetan 220 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 15 (predose) | 5.54 fold change | Standard Deviation 3.49 |
| Cohort 9d: Milademetan 220 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 1 (6 hours postdose) | 3.00 fold change | Standard Deviation 0.88 |
| Cohort 9d: Milademetan 220 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 8 (predose) | 5.13 fold change | Standard Deviation 2.64 |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 8 (predose) | 9.70 fold change | Standard Deviation 7.96 |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 1 (6 hours postdose) | 4.25 fold change | Standard Deviation 1.41 |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 2 (predose) | 5.06 fold change | Standard Deviation 2.62 |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 15 (predose) | 9.28 fold change | Standard Deviation 7.26 |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 21-22 (predose) | 5.88 fold change | Standard Deviation 2.75 |
| Cohort 6b: Milademetan 160 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 2 (predose) | 2.57 fold change | Standard Deviation 0.81 |
| Cohort 6b: Milademetan 160 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 8 (predose) | 4.93 fold change | Standard Deviation 3.32 |
| Cohort 6b: Milademetan 160 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 15 (predose) | 1.33 fold change | Standard Deviation 0.98 |
| Cohort 6b: Milademetan 160 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 21-22 (predose) | 0.48 fold change | — |
| Cohort 6b: Milademetan 160 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 1 (6 hours postdose) | 2.64 fold change | Standard Deviation 0.91 |
| Cohort 7c: Milademetan 160 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 8 (predose) | 1.44 fold change | Standard Deviation 0.36 |
| Cohort 7c: Milademetan 160 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 2 (predose) | 3.84 fold change | Standard Deviation 1.74 |
| Cohort 7c: Milademetan 160 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 1 (6 hours postdose) | 3.36 fold change | Standard Deviation 1.49 |
| Cohort 7c: Milademetan 160 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 15 (predose) | 1.13 fold change | Standard Deviation 0.41 |
| Cohort 7c: Milademetan 160 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 21-22 (predose) | 1.24 fold change | — |
| Cohort 8d: Milademetan 160 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 8 (predose) | 5.63 fold change | Standard Deviation 3.99 |
| Cohort 8d: Milademetan 160 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 2 (predose) | 3.68 fold change | Standard Deviation 2.13 |
| Cohort 8d: Milademetan 160 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 21-22 (predose) | 0.83 fold change | Standard Deviation 0.45 |
| Cohort 8d: Milademetan 160 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 15 (predose) | 5.02 fold change | Standard Deviation 2.2 |
| Cohort 8d: Milademetan 160 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 1 (6 hours postdose) | 2.64 fold change | Standard Deviation 0.87 |
| Cohort 9d: Milademetan 220 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 21-22 (predose) | 1.18 fold change | Standard Deviation 0.6 |
| Cohort 9d: Milademetan 220 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 1 (6 hours postdose) | 4.94 fold change | Standard Deviation 2.22 |
| Cohort 9d: Milademetan 220 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 15 (predose) | 6.61 fold change | Standard Deviation 4.64 |
| Cohort 9d: Milademetan 220 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 2 (predose) | 8.09 fold change | Standard Deviation 3.27 |
| Cohort 9d: Milademetan 220 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone | Day 8 (predose) | 13.68 fold change | Standard Deviation 10.72 |
Secondary
Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan In Combination With 5-Azacitidine (AZA)
Pharmacodynamic biomarker serum macrophage inhibitory cytokine-1 (MIC-1) concentrations were assessed for Cohorts 10e though 13f. Fold change is the ratio of post-baseline MIC-1 values with respect to the baseline values and is the measure of change of MIC-1 from baseline.
Time frame: Day 5 (predose) up to Day 22 (predose), up to approximately 6 years of first participant enrolled
Population: Pharmacodynamic biomarker, MIC-1, was assessed in the Safety Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Milademetan 60 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Day 14 (predose) | 10.82 fold change | Standard Deviation 8.26 |
| Cohort 1: Milademetan 60 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Day 22 (predose) | 2.05 fold change | Standard Deviation 2.34 |
| Cohort 1: Milademetan 60 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Day 5 (6 hours postdose) | 3.12 fold change | Standard Deviation 2.38 |
| Cohort 1: Milademetan 60 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Day 5 (predose) | 1.65 fold change | Standard Deviation 0.72 |
| Cohort 4: Milademetan 160 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Day 14 (predose) | 4.06 fold change | Standard Deviation 0.54 |
| Cohort 4: Milademetan 160 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Day 22 (predose) | 1.38 fold change | Standard Deviation 0.29 |
| Cohort 5: Milademetan 210 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Day 14 (predose) | 8.34 fold change | Standard Deviation 6.14 |
| Cohort 5: Milademetan 210 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Day 5 (predose) | 1.39 fold change | Standard Deviation 0.36 |
| Cohort 5: Milademetan 210 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Day 22 (predose) | 1.81 fold change | Standard Deviation 1.2 |
| Cohort 5: Milademetan 210 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Day 5 (6 hours postdose) | 6.07 fold change | Standard Deviation 2.99 |
| Cohort 9d: Milademetan 220 mg | Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Day 22 (predose) | 1.83 fold change | — |
Secondary
Time to Maximum Concentration (Tmax) Following Administration of Milademetan Alone
Pharmacokinetic parameter time to maximum concentration (Tmax) of milademetan was assessed at select time points.
Time frame: Predose, 1 hour (hr), 2 hr, 3 hr, 6 hr, 8 hr, 10 hr of Cycle 1, Day 1 (Cohorts 1-9d) and Cycle 1, Day 15 (Cohorts 1-5 and 7c) (each cycle is 28 days)
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: Milademetan 60 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan Alone | Cycle 1, Day 1 | 3.00 hours |
| Cohort 1: Milademetan 60 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan Alone | Cycle 1, Day 15 | 3.00 hours |
| Cohort 4: Milademetan 160 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan Alone | Cycle 1, Day 15 | 2.99 hours |
| Cohort 4: Milademetan 160 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan Alone | Cycle 1, Day 1 | 4.39 hours |
| Cohort 5: Milademetan 210 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan Alone | Cycle 1, Day 15 | 3.00 hours |
| Cohort 5: Milademetan 210 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan Alone | Cycle 1, Day 1 | 3.00 hours |
| Cohort 9d: Milademetan 220 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan Alone | Cycle 1, Day 1 | 4.50 hours |
| Cohort 9d: Milademetan 220 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan Alone | Cycle 1, Day 15 | 2.96 hours |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Time to Maximum Concentration (Tmax) Following Administration of Milademetan Alone | Cycle 1, Day 15 | 4.50 hours |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Time to Maximum Concentration (Tmax) Following Administration of Milademetan Alone | Cycle 1, Day 1 | 3.00 hours |
| Cohort 6b: Milademetan 160 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan Alone | Cycle 1, Day 1 | 3.00 hours |
| Cohort 6b: Milademetan 160 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan Alone | Cycle 1, Day 15 | NA hours |
| Cohort 7c: Milademetan 160 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan Alone | Cycle 1, Day 15 | 3.04 hours |
| Cohort 7c: Milademetan 160 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan Alone | Cycle 1, Day 1 | 3.08 hours |
| Cohort 8d: Milademetan 160 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan Alone | Cycle 1, Day 1 | 4.50 hours |
| Cohort 8d: Milademetan 160 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan Alone | Cycle 1, Day 15 | NA hours |
| Cohort 9d: Milademetan 220 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan Alone | Cycle 1, Day 15 | NA hours |
| Cohort 9d: Milademetan 220 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan Alone | Cycle 1, Day 1 | 4.56 hours |
Secondary
Time to Maximum Concentration (Tmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA)
Pharmacokinetic parameter time to maximum concentration (Tmax) was assessed at select time points.
Time frame: Predose, 0.5 hour (hr), 1 hr, 2 hr, 3 hr, 6 hr of Cycle 1, Day 1 (AZA); Predose, 0.5 hr, 1 hr, 2 hr, 3 hr, 4 hr, 6-10 hr of Day 5, Day 7 (predose) (Cohorts 10e and 12e), Day 8 (Cohorts 11f and 13f), and Day 14 (Cohorts 10e-13f) (each cycle is 28 days)
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: Milademetan 60 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 8 | NA hours |
| Cohort 1: Milademetan 60 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 5 | 3.02 hours |
| Cohort 1: Milademetan 60 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 14 | 3.00 hours |
| Cohort 1: Milademetan 60 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 7 | 0.56 hours |
| Cohort 1: Milademetan 60 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 1 | 0.77 hours |
| Cohort 4: Milademetan 160 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 7 | NA hours |
| Cohort 4: Milademetan 160 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 8 | 6.33 hours |
| Cohort 4: Milademetan 160 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 14 | 6.05 hours |
| Cohort 4: Milademetan 160 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 5 | NA hours |
| Cohort 4: Milademetan 160 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 1 | NA hours |
| Cohort 5: Milademetan 210 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 7 | 0.58 hours |
| Cohort 5: Milademetan 210 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 1 | 0.51 hours |
| Cohort 5: Milademetan 210 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 5 | 4.41 hours |
| Cohort 5: Milademetan 210 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 8 | NA hours |
| Cohort 5: Milademetan 210 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 14 | 5.54 hours |
| Cohort 9d: Milademetan 220 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 8 | 3.08 hours |
| Cohort 9d: Milademetan 220 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 5 | NA hours |
| Cohort 9d: Milademetan 220 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 1 | NA hours |
| Cohort 9d: Milademetan 220 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 7 | NA hours |
| Cohort 9d: Milademetan 220 mg | Time to Maximum Concentration (Tmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) | Cycle 1, Day 14 | 6.15 hours |
Secondary
Trough Plasma Concentration (Ctrough) Following Administration of Milademetan Alone
Pharmacokinetic parameter plasma concentration before next dose (Ctrough) of milademetan was assessed at Cycle 1, Day 15 and the geometric means (coefficient of variation %) are presented.
Time frame: Predose, 1 hour (hr), 2 hr, 3 hr, 6 hr, 8 hr, 10 hr of Cycle 1, Day 15 (Cohorts 1-5 and 7c) (each cycle is 28 days)
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Milademetan 60 mg | Trough Plasma Concentration (Ctrough) Following Administration of Milademetan Alone | 197.13 ng/mL | Geometric Coefficient of Variation 23.2 |
| Cohort 4: Milademetan 160 mg | Trough Plasma Concentration (Ctrough) Following Administration of Milademetan Alone | 229.28 ng/mL | Geometric Coefficient of Variation 82 |
| Cohort 5: Milademetan 210 mg | Trough Plasma Concentration (Ctrough) Following Administration of Milademetan Alone | 292.60 ng/mL | Geometric Coefficient of Variation 59.7 |
| Cohort 9d: Milademetan 220 mg | Trough Plasma Concentration (Ctrough) Following Administration of Milademetan Alone | 184.60 ng/mL | Geometric Coefficient of Variation 279.1 |
| Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2 | Trough Plasma Concentration (Ctrough) Following Administration of Milademetan Alone | 507.07 ng/mL | Geometric Coefficient of Variation 24 |
| Cohort 6b: Milademetan 160 mg | Trough Plasma Concentration (Ctrough) Following Administration of Milademetan Alone | NA ng/mL | — |