TerminatedNCT02319369Updated Oct 11, 2021Results posted

Safety, Tolerability and Pharmacokinetics of Milademetan Alone and With 5-Azacitidine (AZA) in Acute Myelogenous Leukemia (AML) or High-Risk Myelodysplastic Syndrome (MDS)

A Phase 1 interventional study of Milademetan and AZA in Acute Myelogenous Leukemia and Myelodysplastic Syndrome, sponsored by Daiichi Sankyo. Terminated at 5 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-10-11.

Sponsored by Daiichi Sankyo · Phase 1, Interventional, and Treatment

Why this study was terminated

This study was terminated based on a business decision by the Sponsor.

Phase: Phase 1
Study type: Interventional
Enrollment: 74
Allocation: Non-randomized
Ages: 18 Years and older
Sex: All

Study 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.

Read the 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

Conditions studied

Acute Myelogenous Leukemia
Myelodysplastic Syndrome

Browse trials for

Keywords

High Risk Myelodysplastic Syndrome
Relapsed/Refractory
Newly Diagnosed
Unfit for Chemotherapy

In context

Leukemia

5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.

This study's enrollment of 74 is above the median of 38 across 4,247 interventional studies indexed under Leukemia.

Browse Leukemia studies →

Lead sponsor

Daiichi Sankyo is the lead sponsor of 316 studies on the registry; 35 are open to participants now.

Of its 51 completed or terminated interventional studies of FDA-regulated products, 38 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

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.
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.
Has protocol-defined adequate renal, hepatic and blood clotting functions.
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.
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.
Is fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects).
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.
Is able and willing to provide bone marrow biopsies/aspirates as requested by the protocol.
Is willing to undergo malignancy genotyping for TP53 mutation, insertion, or deletion at screening.

Exclusion criteria

Exclusion Criteria

Has a diagnosis of acute promyelocytic leukemia.
Has a malignancy that is known to contain a non-synonymous mutation, insertion, or deletion in the TP53 gene determined previously or at screening.
Has presence of central nervous system (CNS) involvement of leukemia or a history of primary CNS leukemia.
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.
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.
Has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals, known human immunodeficiency virus infection, or active hepatitis B or C infection.
Has a concomitant medical condition that would increase the risk of toxicity.
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).
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.
Is receiving concomitant treatment with a strong inhibitor or inducer of cytochrome P450 3A4/5.
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].
Had major surgery within 4 weeks prior to study drug treatment.
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.
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).
Is pregnant or breastfeeding.
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.
Prior treatment with an MDM2 inhibitor.

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Sequential assignment
Masking: None (open label)
Enrollment: 74 participants (actual)

Study arms

Experimental
Part 1, Milademetan Alone
Participants receive milademetan alone with different dose schedules
Drug: Milademetan
Experimental
Part 1A, Milademetan with 5-azacytidine (AZA)
Participants receive milademetan in combination with 5-azacytidine (AZA), with different dose schedules
Drug: Milademetan · Drug: AZA
Experimental
Part 2, Cohort 1
Participants with refractory or relapsed acute myelogenous leukemia (AML) receive the recommended dose for Part 2 of milademetan or milademetan with5-azacytidine (AZA)
Drug: AZA · Drug: Milademetan
Experimental
Part 2, Cohort 2
Participants with newly diagnosed acute myelogenous leukemia (AML) unfit for intensive chemotherapy receive the recommended dose for Part 2 of milademetan or milademetan with 5-azacytidine (AZA)
Drug: AZA · Drug: Milademetan
Experimental
Part 2, Cohort 3
Participants with high-risk myelodysplastic syndrome (MDS) receive the recommended dose for Part 2 of milademetan or milademetan with 5-azacytidine (AZA)
Drug: AZA · Drug: Milademetan

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
Also known as: Oral MDM2 Inhibitor
DrugAZA
AZA will be administered at 75 mg/m\^2 subcutaneously or intravenously
Also known as: 5-Azacitidine
DrugMilademetan
Milademetan will be administered daily as oral capsules or as a combination of multiple oral capsules containing 5, 20, 80, and/or 200 mg. An alternate combination of 30 mg, 80 mg, and/or 100 mg milademetan may be utilized.
Also known as: Oral MDM2 Inhibitor

What researchers measure

Primary outcomes

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
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

Secondary outcomes

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)
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)
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)
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)
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)
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)
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)
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
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

Results

Posted Oct 11, 2021

Participant flow

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.

Participant flow — Overall Study
Milestone	Cohort 1: Milademetan 60 mg	Cohort 2: Milademetan 90 mg	Cohort 3: Milademetan 120 mg	Cohort 4: Milademetan 160 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 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 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2
Started	7	6	11	8	5	7	3	6	4	9	3	4	1
Completed	7	6	11	8	5	7	3	6	4	9	3	4	1
Not completed	0	0	0	0	0	0	0	0	0	0	0	0	0

Outcome measures

PrimaryNumber 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
Reported as:: Count of participants · Participants

Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA)
Participants	Cohort 1: Milademetan 60 mg	Cohort 4: Milademetan 160 mg	Cohort 5: Milademetan 210 mg	Cohort 9d: Milademetan 220 mg	Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2
Participants with TEAEs classified as DLTs	1	2	3	2	2
Nausea	0	0	1	2	0
Fatigue	0	0	1	0	2
Cellulitis	0	0	1	0	0
Diarrhoea	0	1	0	0	0
Hypokalaemia	0	1	0	0	0
Renal failure	0	0	1	0	0
Vomiting	1	0	0	0	0
Syncope	0	0	0	0	1

PrimaryNumber 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
Reported as:: Count of participants · Participants

Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA)
Participants	Cohort 1: Milademetan 60 mg	Cohort 2: Milademetan 90 mg	Cohort 3: Milademetan 120 mg	Cohort 4: Milademetan 160 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 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 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2
Any TEAEs	7	6	11	8	5	7	3	6	4	9	3	4	1
Nausea	5	4	8	6	4	3	2	4	3	5	2	2	1
Diarrhoea	2	2	8	5	3	4	2	3	3	1	2	1	0
Vomiting	2	1	4	4	3	2	2	3	3	3	2	0	0
Fatigue	2	1	5	5	3	2	0	1	1	3	2	2	0
Thrombocytopenia	2	1	4	5	1	1	0	0	1	0	0	3	0
Oedema peripheral	1	0	4	2	1	3	1	1	1	1	1	1	0
Anaemia	2	3	3	3	1	1	0	0	0	0	0	0	0
Decreased appetite	2	0	2	3	3	2	0	1	0	3	2	0	0
Hypokalaemia	0	1	1	4	3	2	0	0	1	1	0	1	0
Lung infection	0	1	2	2	0	2	1	1	2	3	3	0	0
Neutropenia	1	2	2	3	1	0	0	0	1	1	0	1	0
Hypomagnesaemia	0	1	3	1	2	2	0	0	0	0	0	0	0
Hypotension	2	2	2	1	1	0	0	0	1	3	1	1	0
Pneumonia	3	1	1	3	0	0	0	1	0	3	1	1	0
Dyspnoea	0	1	2	1	3	1	0	0	0	3	3	0	0
Sepsis	2	0	1	1	0	1	1	1	1	2	0	0	0
Abdominal pain	2	1	0	0	0	2	0	2	0	3	1	1	0
Asthenia	1	0	1	1	2	1	0	0	1	0	0	0	0
Dehydration	1	0	1	1	1	1	0	0	1	2	0	0	0
Dizziness	1	1	0	2	2	0	0	0	0	2	1	1	0
Febrile neutropenia	1	0	3	1	1	0	0	0	0	0	0	0	0
Hyperuricaemia	2	1	0	1	2	0	0	0	0	0	0	0	0
Malaise	1	0	1	0	1	1	1	1	0	0	0	0	0
Cough	0	0	0	0	0	0	0	0	0	4	3	0	0
Constipation	0	0	0	0	0	0	0	0	0	2	2	1	1
Contusion	0	0	0	0	0	0	0	0	0	2	2	0	0
Myalgia	0	0	0	0	0	0	0	0	0	3	1	0	0
Epistaxis	0	0	0	0	0	0	0	0	0	2	0	1	0
Headache	0	0	0	0	0	0	0	0	0	2	1	0	0
Hypophosphataemia	0	0	0	0	0	0	0	0	0	2	1	0	0
Muscular weakness	0	0	0	0	0	0	0	0	0	2	1	0	0
Rash maculo-papular	0	0	0	0	0	0	0	0	0	0	0	3	0
Rhinorrhoea	0	0	0	0	0	0	0	0	0	1	2	0	0
Alanine aminotransferase increased	0	0	0	0	0	0	0	0	0	1	1	0	0
Athralgia	0	0	0	0	0	0	0	0	0	1	1	0	0
Death	0	0	0	0	0	0	0	0	0	0	2	0	0
Depression	0	0	0	0	0	0	0	0	0	1	0	1	0
Device-related infection	0	0	0	0	0	0	0	0	0	2	0	0	0
Escherichia infection	0	0	0	0	0	0	0	0	0	2	0	0	0
Fluid overload	0	0	0	0	0	0	0	0	0	1	1	0	0
Hemorrhoids	0	0	0	0	0	0	0	0	0	2	0	0	0
Hyponatraemia	0	0	0	0	0	0	0	0	0	0	1	1	0
Insomnia	0	0	0	0	0	0	0	0	0	1	1	0	0
Oropharyngeal pain	0	0	0	0	0	0	0	0	0	2	0	0	0
Pancytopenia	0	0	0	0	0	0	0	0	0	2	0	0	0
Pneumonia fungal	0	0	0	0	0	0	0	0	0	0	1	1	0
Pyrexia	0	0	0	0	0	0	0	0	0	1	1	0	0

SecondaryMaximum 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)
Reported as:: Geometric mean · ng/mL

Maximum Plasma Concentration (Cmax) Following Administration of Milademetan Alone
ng/mL	Cohort 1: Milademetan 60 mg	Cohort 2: Milademetan 90 mg	Cohort 3: Milademetan 120 mg	Cohort 4: Milademetan 160 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
Cycle 1, Day 1	386.0 ± 42.2	342.5 ± 23.4	505.9 ± 56.8	622.3 ± 94.5	747.9 ± 48.1	440.0 ± 74.7	758.1 ± 44.8	657.0 ± 27.2	1607.4 ± 34.4
Cycle 1, Day 15	498.5 ± 40.3	562.6 ± 58.6	614.3 ± 55.3	753.8 ± 79.8	1329.2 ± 21.9	NA ± NA	669.2 ± 46.0	NA ± NA	NA ± NA

SecondaryMaximum 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)
Reported as:: Geometric mean · ng/mL

Maximum Plasma Concentration (Cmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA)
ng/mL	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 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2
Cycle 1, Day 1	527.0 ± 61.9	NA ± NA	707.0 ± 37.7	NA ± NA
Cycle 1, Day 5	704.8 ± 57.6	NA ± NA	1019.6 ± 72.2	NA ± NA
Cycle 1, Day 7	702.5 ± 46.4	NA ± NA	769.8 ± 46.7	NA ± NA
Cycle 1, Day 8	NA ± NA	327.5 ± 51.2	NA ± NA	266.0 ± NA
Cycle 1, Day 14	1488.6 ± 55.2	1057.9 ± 20.4	1448.2 ± 57.2	1190.0 ± NA

SecondaryTime 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)
Reported as:: Median · hours

Time to Maximum Concentration (Tmax) Following Administration of Milademetan Alone
hours	Cohort 1: Milademetan 60 mg	Cohort 2: Milademetan 90 mg	Cohort 3: Milademetan 120 mg	Cohort 4: Milademetan 160 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
Cycle 1, Day 1	3.00 (2.00 to 6.25)	4.39 (1.98 to 6.08)	3.00 (2.00 to 6.25)	4.50 (1.90 to 6.07)	3.00 (3.00 to 8.07)	3.00 (2.05 to 10.00)	3.08 (2.00 to 6.00)	4.50 (3.00 to 6.00)	4.56 (3.00 to 6.17)
Cycle 1, Day 15	3.00 (2.00 to 3.28)	2.99 (2.00 to 6.00)	3.00 (2.00 to 6.00)	2.96 (1.08 to 6.00)	4.50 (2.92 to 6.00)	NA (NA to NA)	3.04 (3.00 to 3.08)	NA (NA to NA)	NA (NA to NA)

SecondaryTime 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)
Reported as:: Median · hours

Time to Maximum Concentration (Tmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA)
hours	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 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2
Cycle 1, Day 1	0.77 (0.48 to 2.00)	NA (NA to NA)	0.51 (0.48 to 0.58)	NA (NA to NA)
Cycle 1, Day 5	3.02 (2.05 to 6.07)	NA (NA to NA)	4.41 (2.10 to 8.00)	NA (NA to NA)
Cycle 1, Day 7	0.56 (0.48 to 0.98)	NA (NA to NA)	0.58 (0.50 to 1.00)	NA (NA to NA)
Cycle 1, Day 8	NA (NA to NA)	6.33 (6.07 to 8.97)	NA (NA to NA)	3.08 (3.08 to 3.08)
Cycle 1, Day 14	3.00 (2.05 to 10.00)	6.05 (3.17 to 8.00)	5.54 (3.08 to 8.00)	6.15 (6.15 to 6.15)

SecondaryTrough 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)
Reported as:: Geometric mean · ng/mL

Trough Plasma Concentration (Ctrough) Following Administration of Milademetan Alone
ng/mL	Cohort 1: Milademetan 60 mg	Cohort 2: Milademetan 90 mg	Cohort 3: Milademetan 120 mg	Cohort 4: Milademetan 160 mg	Cohort 5: Milademetan 210 mg	Cohort 7c: Milademetan 160 mg
Trough Plasma Concentration (Ctrough) Following Administration of Milademetan Alone	197.13 ± 23.2	229.28 ± 82.0	292.60 ± 59.7	184.60 ± 279.1	507.07 ± 24.0	NA ± NA

SecondaryArea 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)
Reported as:: Geometric mean · ng*h/mL

Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan Alone
ng*h/mL	Cohort 1: Milademetan 60 mg	Cohort 2: Milademetan 90 mg	Cohort 3: Milademetan 120 mg	Cohort 4: Milademetan 160 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
Cycle 1, Day 1	4646.7 ± 47.7	4478.1 ± 31.2	6585.4 ± 54.8	8315.1 ± 101.2	9794.0 ± 39.4	7222.5 ± 43.1	10165.6 ± 64.6	8973.9 ± 28.1	20893.9 ± 23.2
Cycle 1, Day 15	7244.6 ± 28.9	8392.9 ± 56.5	9854.9 ± 54.6	10710.8 ± 54.2	20330.2 ± 15.9	NA ± NA	7714.3 ± 30.5	NA ± NA	NA ± NA

SecondaryArea 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)
Reported as:: Geometric mean · ng*h/mL

Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA)
ng*h/mL	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
Cycle 1, Day 5	8238.7 ± 43.0	NA ± NA	21299.3 ± 16.3
Cycle 1, Day 14	22563.8 ± 52.9	15755.5 ± 29.4	19967.5 ± 18.5

SecondarySerum 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
Reported as:: Mean · fold change

Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone
fold change	Cohort 1: Milademetan 60 mg	Cohort 2: Milademetan 90 mg	Cohort 3: Milademetan 120 mg	Cohort 4: Milademetan 160 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
Day 1 (6 hours postdose)	3.14 ± 1.23	2.78 ± 0.95	3.36 ± 1.38	3.00 ± 0.88	4.25 ± 1.41	2.64 ± 0.91	3.36 ± 1.49	2.64 ± 0.87	4.94 ± 2.22
Day 2 (predose)	2.53 ± 0.83	3.31 ± 1.25	3.97 ± 2.71	3.44 ± 1.63	5.06 ± 2.62	2.57 ± 0.81	3.84 ± 1.74	3.68 ± 2.13	8.09 ± 3.27
Day 8 (predose)	4.13 ± 2.46	6.35 ± 4.61	7.41 ± 7.17	5.13 ± 2.64	9.70 ± 7.96	4.93 ± 3.32	1.44 ± 0.36	5.63 ± 3.99	13.68 ± 10.72
Day 15 (predose)	2.88 ± 0.64	5.64 ± 4.94	6.04 ± 3.49	5.54 ± 3.49	9.28 ± 7.26	1.33 ± 0.98	1.13 ± 0.41	5.02 ± 2.20	6.61 ± 4.64
Day 21-22 (predose)	3.49 ± 1.88	4.61 ± 2.66	4.57 ± 3.53	6.57 ± 4.22	5.88 ± 2.75	0.48 ± NA	1.24 ± NA	0.83 ± 0.45	1.18 ± 0.60

SecondarySerum 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
Reported as:: Mean · fold change

Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan In Combination With 5-Azacitidine (AZA)
fold change	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 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2
Day 5 (predose)	1.65 ± 0.72	—	1.39 ± 0.36	—
Day 5 (6 hours postdose)	3.12 ± 2.38	—	6.07 ± 2.99	—
Day 14 (predose)	10.82 ± 8.26	4.06 ± 0.54	8.34 ± 6.14	—
Day 22 (predose)	2.05 ± 2.34	1.38 ± 0.29	1.81 ± 1.20	1.83 ± NA

Adverse events

Collected over Treatment-emergent adverse events (TEAEs) were collected from the date the participant signed the informed consent form up to 30 days after the last dose of study drug, up to approximately 6 years of first participant enrolled.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Cohort 1: Milademetan 60 mg	1/7 (14.3%)	4/7 (57.1%)	7/7 (100%)
Cohort 2: Milademetan 90 mg	0/6 (0%)	5/6 (83.3%)	6/6 (100%)
Cohort 3: Milademetan 120 mg	1/11 (9.1%)	9/11 (81.8%)	11/11 (100%)
Cohort 4: Milademetan 160 mg	1/8 (12.5%)	5/8 (62.5%)	8/8 (100%)
Cohort 5: Milademetan 210 mg	1/5 (20%)	5/5 (100%)	5/5 (100%)
Cohort 6b: Milademetan 160 mg	1/7 (14.3%)	4/7 (57.1%)	7/7 (100%)
Cohort 7c: Milademetan 160 mg	1/3 (33.3%)	2/3 (66.7%)	3/3 (100%)
Cohort 8d: Milademetan 160 mg	1/6 (16.7%)	3/6 (50%)	6/6 (100%)
Cohort 9d: Milademetan 220 mg	2/4 (50%)	2/4 (50%)	4/4 (100%)
Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2	2/9 (22.2%)	9/9 (100%)	9/9 (100%)
Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2	2/3 (66.7%)	3/3 (100%)	3/3 (100%)
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	1/4 (25%)	4/4 (100%)	4/4 (100%)
Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2	0/1 (0%)	0/1 (0%)	1/1 (100%)

Most frequent serious events

Showing 10 of 53

Most frequent serious events
Event	Cohort 1: Milademetan 60 mg	Cohort 2: Milademetan 90 mg	Cohort 3: Milademetan 120 mg	Cohort 4: Milademetan 160 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 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 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2
Lung infectionInfections and infestations	0/7	0/6	2/11	1/8	0/5	2/7	1/3	1/6	2/4	3/9	3/3	0/4	0/1
DeathGeneral disorders	0/7	0/6	0/11	0/8	0/5	0/7	0/3	0/6	0/4	0/9	2/3	0/4	0/1
PneumoniaInfections and infestations	2/7	1/6	0/11	3/8	0/5	0/7	0/3	1/6	0/4	2/9	1/3	1/4	0/1
SepsisInfections and infestations	2/7	0/6	1/11	1/8	0/5	0/7	1/3	1/6	1/4	2/9	0/3	0/4	0/1
BacteraemiaInfections and infestations	0/7	0/6	1/11	0/8	1/5	0/7	1/3	0/6	0/4	0/9	0/3	0/4	0/1
Pneumonia fungalInfections and infestations	0/7	1/6	0/11	0/8	0/5	0/7	0/3	1/6	0/4	0/9	1/3	1/4	0/1
DiarrhoeaGastrointestinal disorders	0/7	0/6	0/11	1/8	0/5	0/7	1/3	0/6	0/4	0/9	0/3	0/4	0/1
Parainfluenzae virus infectionInfections and infestations	0/7	0/6	0/11	0/8	0/5	0/7	0/3	0/6	0/4	0/9	1/3	0/4	0/1
Staphylococcal sepsisInfections and infestations	0/7	0/6	0/11	0/8	0/5	0/7	0/3	0/6	0/4	0/9	1/3	0/4	0/1
Swelling faceSkin and subcutaneous tissue disorders	0/7	0/6	0/11	0/8	0/5	0/7	0/3	0/6	0/4	0/9	1/3	0/4	0/1

Most frequent other events

Showing 10 of 226

Most frequent other events
Event	Cohort 1: Milademetan 60 mg	Cohort 2: Milademetan 90 mg	Cohort 3: Milademetan 120 mg	Cohort 4: Milademetan 160 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 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 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2
NauseaGastrointestinal disorders	5/7	4/6	8/11	6/8	4/5	3/7	2/3	4/6	3/4	5/9	2/3	2/4	1/1
ConstipationGastrointestinal disorders	0/7	0/6	1/11	1/8	0/5	1/7	0/3	0/6	0/4	2/9	2/3	1/4	1/1
Lung infectionInfections and infestations	0/7	1/6	2/11	2/8	0/5	2/7	1/3	1/6	2/4	3/9	3/3	0/4	0/1
DyspnoeaRespiratory, thoracic and mediastinal disorders	0/7	1/6	2/11	1/8	3/5	1/7	0/3	0/6	0/4	3/9	3/3	0/4	0/1
CoughRespiratory, thoracic and mediastinal disorders	1/7	0/6	1/11	0/8	0/5	0/7	1/3	0/6	0/4	4/9	3/3	0/4	0/1
FallInjury, poisoning and procedural complications	0/7	0/6	1/11	1/8	1/5	0/7	0/3	0/6	0/4	0/9	0/3	0/4	1/1
DiarrhoeaGastrointestinal disorders	2/7	2/6	8/11	5/8	3/5	4/7	2/3	3/6	3/4	1/9	2/3	1/4	0/1
VomitingGastrointestinal disorders	2/7	1/6	4/11	4/8	3/5	2/7	2/3	3/6	3/4	3/9	2/3	0/4	0/1
ThrombocytopeniaBlood and lymphatic system disorders	2/7	1/6	4/11	5/8	1/5	1/7	0/3	0/6	1/4	0/9	0/3	3/4	0/1
Rash maculo-papularSkin and subcutaneous tissue disorders	0/7	0/6	0/11	0/8	1/5	1/7	0/3	0/6	0/4	0/9	0/3	3/4	0/1

Baseline characteristics

Baseline demographics were assessed in the Enrolled Analysis Set.

Age, Continuous
Age, Continuous(years)	Cohort 1: Milademetan 60 mg	Cohort 2: Milademetan 90 mg	Cohort 3: Milademetan 120 mg	Cohort 4: Milademetan 160 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 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 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2	Total
Mean	67.0 ± 14.7	63.8 ± 10.6	61.8 ± 15.6	70.4 ± 6.1	69.2 ± 7.2	71.3 ± 6.4	66.7 ± 7.6	61.8 ± 20.1	72.0 ± 8.2	60.3 ± 19.8	49.3 ± 25.4	70.8 ± 7.1	60.0 ± NA	66.6 ± 12.1

Age, Customized
Age, Customized(Participants)	Cohort 1: Milademetan 60 mg	Cohort 2: Milademetan 90 mg	Cohort 3: Milademetan 120 mg	Cohort 4: Milademetan 160 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 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 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2	Total
≤65 years	4	4	5	2	1	1	1	3	1	5	2	1	1	31
>65 years	3	2	6	6	4	6	2	3	3	4	1	3	0	43

Sex: Female, Male
Sex: Female, Male(Participants)	Cohort 1: Milademetan 60 mg	Cohort 2: Milademetan 90 mg	Cohort 3: Milademetan 120 mg	Cohort 4: Milademetan 160 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 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 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2	Total
Female	4	2	3	3	1	2	1	1	3	6	1	1	1	29
Male	3	4	8	5	4	5	2	5	1	3	2	3	0	45

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Cohort 1: Milademetan 60 mg	Cohort 2: Milademetan 90 mg	Cohort 3: Milademetan 120 mg	Cohort 4: Milademetan 160 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 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 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2	Total
American Indian or Alaska Native	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Asian	1	0	1	0	0	0	1	1	0	0	0	0	0	4
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Black or African American	0	0	0	0	1	1	1	0	0	0	2	0	0	5
White	6	6	9	6	4	6	1	4	4	8	1	4	1	60
More than one race	0	0	1	2	0	0	0	1	0	1	0	0	0	5
Unknown or Not Reported	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Region of Enrollment
Region of Enrollment(participants)	Cohort 1: Milademetan 60 mg	Cohort 2: Milademetan 90 mg	Cohort 3: Milademetan 120 mg	Cohort 4: Milademetan 160 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 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 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2	Total
United States	7	6	11	8	5	7	3	6	4	9	3	4	1	74

Study locations

5 sites

City of Hope National Medical Center
Duarte, California 91010, United States
University of California San Francisco Medical Center
San Francisco, California 94143, United States
University of Kansas Cancer Center
Fairway, Kansas 66205, United States
Roswell Park Comprehensive Cancer Center
Buffalo, New York 14263, United States
M D Anderson Cancer Center
Houston, Texas 77031, United States

References and documents

Study documents

Protocol and statistical analysis plan · Mar 6, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Supporting information: Study protocol, Sap, Csr

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Oct 11, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02319369
Lead sponsor: Daiichi Sankyo
Responsible party: Sponsor
First posted: Dec 18, 2014
Start date: Nov 25, 2014
Primary completion: Aug 21, 2020
Completion: Aug 21, 2020
Results posted: Oct 11, 2021
Last update: Oct 11, 2021

Study contacts

Global Clinical Leader

study director · Daiichi Sankyo

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is terminated, as verified in Sep 2021. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Leukemia→

Other studies from this sponsor

Daiichi Sankyo

Start the discussion