Advanced Solid Tumor, Lymphoma
Conditions
Brief summary
This will be a Phase 1, open-label study of milademetan to assess its safety and tolerability, identify a maximum tolerated dose (MTD)/tentative recommended phase 2 dose (RP2D), and assess its pharmacokinetic (PK)/ pharmacodynamic (PDy) properties in participants with advanced solid tumors or lymphomas. Approximately 5 US sites are planned for Part 1 (Dose Escalation) and Part 2 (Dose Expansion). The same sites are planned to participate for both parts.
Interventions
DRUGMilademetan
DS-3032b will be administered as an oral capsule. It will be supplied in 5, 20, 80, and/or 200 mg capsules individually packaged in desiccant-embedded aluminum blisters.
Sponsors
Daiichi Sankyo
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Dose Escalation Cohorts (Part 1) * Has a histologically or cytologically documented advanced solid tumor or lymphoma that has relapsed from or is refractory to standard treatment, or for which no standard treatment is available. * Participants with melanoma who are ineligible to receive or have declined ipilimumab treatment or who are refractory or intolerant to ipilimumab may enroll. * Participants with certain tumor types such as those with high prevalence of MDM2 amplification or overexpression (eg, well-differentiated \[WD\]/dedifferentiated \[DD\] liposarcoma) may be preferentially enrolled in Part 1. Dose Expansion Cohort (Part 2) * Has a histologically or cytologically documented advanced melanoma or diffuse large B cell lymphoma (DLBCL), with measurable disease that is refractory to standard treatment or for which no standard treatment is available. * Participants with melanoma who are ineligible to receive or have declined ipilimumab treatment or who are refractory or intolerant to ipilimumab may enroll. * Participants with DLBCL who have failed, been deemed ineligible for, or refused autologous stem cell transplantation may enroll. * Man or woman ≥ 18 years old. * Has an Eastern Cooperative Oncology Group (ECOG) performance status 0-1. * Has adequate bone marrow function, defined as: * Platelet count ≥ 100 x 10\^9/L * Hemoglobin ≥ 9.0 g/dL * Absolute neutrophil count ≥ 1.5 x 10\^9/L. * Has adequate renal function, defined as creatinine clearance ≥ 60 mL/min, as calculated using the modified Cockcroft Gault equation, (\[{140 - age in years} × {actual weight in kg}\] divided by \[{72 × serum creatinine in mg/dL} multiply by 0.85 if female\]), OR creatinine ≤ 1.5 x ULN. * Has adequate hepatic function, defined as: * AST/ALT levels ≤ 3 x ULN (if liver metastases are present, ≤ 5 x ULN) * Bilirubin ≤ 1.5 x ULN. * Has adequate blood clotting function, defined as International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN. * Participant should be able to provide written informed consent, comply with protocol visits and procedures, be able to take oral medication, and not have any active infection or comorbidity that would interfere with therapy. * Participant (male and female) of childbearing/reproductive potential must agree to use double-barrier contraceptive measures or avoid intercourse during the study and for 90 days after the last dose of study drug. * Participant must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects) and must sign and date an IRB \[Institutional Review Board\]-approved Informed consent Form \[ICF\] (including Health Insurance Portability and Accountability Act authorization, if applicable) before performance of any study specific procedures or tests. * Is willing to provide and there is confirmed availability of pre-existing diagnostic or resected tumor samples, such as paraffin-embedded sections. Providing fresh tumor biopsy is optional for participants in Dose Escalation cohorts. * Is willing to undergo tumor genotyping for TP53 mutation, insertion, or deletion at screening. Confirmation of TP53 nonmutant status is encouraged, but not required prior to milademetan dosing. * Is willing to provide additional archived samples for comprehensive genomic and/or proteomic analyses if the participant has a partial response/complete response to milademetan treatment. * Is willing to undergo pre-treatment tumor biopsies (Part 2 only)
Exclusion criteria
* Has a tumor that contains an inactivating mutation, insertion, or deletion in the TP53 gene determined previously or at screening. * Has a history of primary central nervous system malignancy. * Has gastrointestinal conditions that could affect the absorption of milademetan in the opinion of the Investigator. * Has an uncontrolled infection requiring intravenous antibiotics, antivirals, or antifungals, known human immunodeficiency virus infection, or active hepatitis B or C infection. * Has received an allogeneic bone marrow or allogeneic stem cell transplant. * Has a concomitant medical condition that would increase the risk of toxicity, in the opinion of the Investigator or Sponsor. * Has clinically active brain metastases, defined as untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. Participants with treated brain metastases that are no longer symptomatic and who require no treatment with steroids may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 4 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment (2 weeks for stereotactic radiotherapy). * Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE v4, grade ≤ 1 or baseline. Participants with chronic grade 2 toxicities may be eligible per the discretion of the Investigator and Sponsor (eg, grade 2 chemotherapy-induced neuropathy). * Had an autologous transplant within 3 months of starting study drug treatment. * Is receiving concomitant treatment with a strong inducer of CYP3A. * Had systemic treatment with anticancer therapy, antibody-based therapy, retinoid therapy, or hormonal therapy within 3 weeks before study drug treatment; or treatment with nitrosoureas or mitomycin C within 6 weeks before study drug treatment; or treatment with small-molecule targeted agents within 2 weeks before study drug treatment. Previous and concurrent use of hormone replacement therapy, the use of gonadotropin releasing hormone modulators for prostate cancer, and the use of somatostatin analogs for neuroendocrine tumors are permitted if such therapy has not been changed within 8 weeks before study drug treatment. * Had therapeutic radiation therapy or major surgery within 4 weeks before study drug treatment or palliative radiation therapy within 2 weeks before study drug treatment. * Participated in a therapeutic clinical study within 3 weeks before study drug treatment, or current participation in other therapeutic investigational procedures. * Prolongation of corrected QT interval by Fridericia's method (QTcF) at rest, where the mean QTcF interval is \> 450 milliseconds (ms) for males and \> 470 ms for females based on triplicate ECG. * Pregnant or breastfeeding. * Substance abuse or medical, psychological, or social conditions that, in the opinion of the Investigator, may interfere with the participant's participation in the clinical study or evaluation of the clinical study results. * Prior treatment with an MDM2 inhibitor.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Screening until end of treatment visit, up to approximately 7 years 2 months | A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that emerged during the treatment period (from first dose date until 30 days after the last dosing date), having been absent at pretreatment; or reemerged during treatment, having been present at baseline, but stopped prior to treatment; or worsened in severity after starting treatment relative to the pretreatment state, when the AE was continuous. |
| Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Cycle 1, Day 1 to Day 28 (each cycle, 28 days) | A dose-limiting toxicity (DLT) was defined as any treatment-emergent AE (TEAE) not attributable to the participant's disease or a disease-related processes that occurred during the observation period (Cycle 1) in each dose-level cohort and was Grade 3 or higher according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0, with a few exceptions. |
| Number of Participants With Melanoma and Diffuse Large B Cell Lymphoma Who Achieved Objective Response | Screening up to Cycle 3 and beyond, Day 1 (each cycle, 28 days) | Tumor response was assessed using RECIST Version 1.1 (in solid tumor participants with measurable disease) or treatment response using the revised International Working Group criteria 7 (in participants with lymphoma). For RECIST, complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. Objective response rate (ORR) was the sum of CR and PR rates. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Parameter Apparent Clearance (CL/F) of Milademetan In Participants Receiving Milademetan | Escalation:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,6-8 hours(h);Cycle 2,Day 1 Predose,1,3,6-8h,30 days after last dose; Expansion:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,4,6,8h;Cycle 2,Day 1 Predose,1,2,3,4,6,8h and Day 2 (each cycle, 28 days) | Plasma pharmacokinetic parameters of DS-3032a were calculated using noncompartmental methods. |
| Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of Milademetan In Participants Receiving Milademetan | Escalation:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,6-8 hours(h);Cycle 2,Day 1 Predose,1,3,6-8h,30 days after last dose; Expansion:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,4,6,8h;Cycle 2,Day 1 Predose,1,2,3,4,6,8h and Day 2 (each cycle, 28 days) | Plasma pharmacokinetic parameters of DS-3032a were calculated using noncompartmental methods. |
| Mean Fold Change From Baseline in Serum MIC-1 Levels in Participants Receiving Milademetan | Cycle 1, Day 15 and Cycle 1, Days 18 to 21 (each cycle is 28 days) | Mean fold change in macrophage inhibitory cytokine-1 (MIC-1) levels in serum from baseline are summarized using descriptive statistics by cohort. |
| Pharmacokinetic Parameter Elimination Terminal Half Life Half-Life (T1/2) of Milademetan In Participants Receiving Milademetan | Escalation:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,6-8 hours(h);Cycle 2,Day 1 Predose,1,3,6-8h,30 days after last dose; Expansion:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,4,6,8h;Cycle 2,Day 1 Predose,1,2,3,4,6,8h and Day 2 (each cycle, 28 days) | Plasma pharmacokinetic parameters of DS-3032a were calculated using noncompartmental methods. |
| Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | Escalation:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,6-8 hours(h);Cycle 2,Day 1 Predose,1,3,6-8h,30 days after last dose; Expansion:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,4,6,8h;Cycle 2,Day 1 Predose,1,2,3,4,6,8h and Day 2 (each cycle, 28 days) | Area under the curve from time 0 to 24 hours (AUC0-24), time 0 to infinity (AUCinf), and to the last measurable concentration (AUClast). Plasma pharmacokinetic parameters of DS-3032a were calculated using noncompartmental methods. |
| Pharmacokinetic Parameter Time to Reach Maximum Plasma Concentration (Tmax) of Milademetan In Participants Receiving Milademetan | Escalation:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,6-8 hours(h);Cycle 2,Day 1 Predose,1,3,6-8h,30 days after last dose; Expansion:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,4,6,8h;Cycle 2,Day 1 Predose,1,2,3,4,6,8h and Day 2 (each cycle, 28 days) | Plasma pharmacokinetic parameters of DS-3032a were calculated using noncompartmental methods. |
Countries
United States
Participant flow
Recruitment details
A total of 107 participants who met all inclusion criteria and no exclusion criteria were enrolled and received treatment.
Pre-assignment details
Dose escalation of milademetan to determine the maximum tolerated dose started with an initial accelerated titration design and then switched to a Bayesian logistic regression model with escalation with overdose control.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: 15 mg/Day Milademetan Participants who received 15 mg/day milademetan daily (QD) x 21/28 days. | 3 |
| Cohort 2: 30 mg/Day Milademetan Participants who received 30 mg/day milademetan daily (QD) x 21/28 days. | 1 |
| Cohort 3: 60 mg/Day Milademetan Participants who received 60 mg/day milademetan daily (QD) x 21/28 days. | 1 |
| Cohort 4: 120 mg/Day Milademetan Participants who received 120 mg/day milademetan daily (QD) x 21/28 days. | 13 |
| Cohort 5: 240 mg/Day Milademetan Participants who received 240 mg/day milademetan daily (QD) x 21/28 days. | 2 |
| Cohort 6: 160 mg/Day Milademetan Participants who received 160 mg/day milademetan daily (QD) x 21/28 days. | 5 |
| Cohort 7b: 90 mg/Day Milademetan Participants who received 90 mg/day milademetan daily (QD) x 28/28 days. | 9 |
| Cohort 8c: 90 mg/Day Milademetan Participants who received 90 mg/day milademetan daily (QD) x 21/28 days. | 15 |
| Cohort 9d: 120 mg/Day Milademetan Participants who received 120 mg/day milademetan daily (QD) x 7/28 days. | 6 |
| Cohort 10e: 120 mg/Day Milademetan Participants who received 120 mg/day milademetan daily (QD) x 3/14 days x 2 in a 28-day cycle. | 3 |
| Cohort 11e: 200 mg/Day Milademetan Participants who received 200 mg/day milademetan daily (QD) x 3/14 days x 2 in a 28-day cycle. | 3 |
| Cohort 12d: 200 mg/Day Milademetan Participants who received 200 mg/day milademetan daily (QD) x 7/28 days. | 3 |
| Cohort 13e: 260 mg/Day Milademetan Participants who received 260 mg/day milademetan daily (QD) x 3/14 days x 2 in a 28-day cycle. | 20 |
| Cohort 14e: 340 mg/Day Milademetan Participants who received 340 mg/day milademetan daily (QD) x 3/14 days x 2 in a 28-day cycle. | 3 |
| Expansion Cohort: 120 mg/Day Milademetan Participants who received 120 mg/day milademetan daily (QD) x 21/28 days. | 20 |
| Total | 107 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Dose Escalation | Adverse Event | 0 | 0 | 0 | 4 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Dose Escalation | Clinical progression | 0 | 1 | 0 | 2 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 2 | 1 | 0 |
| Dose Escalation | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 0 |
| Dose Escalation | Progressive disease | 2 | 0 | 1 | 6 | 1 | 0 | 3 | 10 | 4 | 2 | 3 | 3 | 13 | 1 | 0 |
| Dose Escalation | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Escalation | Study terminated by sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 3 | 0 | 0 |
| Dose Escalation | TP53 gene nonsynonymous mutation, insertion, or deletion detected | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Escalation | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 3 | 2 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Expansion | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Dose Expansion | Clinical progression | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 6 |
| Dose Expansion | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Dose Expansion | Progressive disease | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 11 |
| Dose Expansion | TP53 gene nonsynonymous mutation, insertion, or deletion detected | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Cohort 2: 30 mg/Day Milademetan | Cohort 3: 60 mg/Day Milademetan | Cohort 4: 120 mg/Day Milademetan | Cohort 5: 240 mg/Day Milademetan | Cohort 6: 160 mg/Day Milademetan | Cohort 7b: 90 mg/Day Milademetan | Cohort 8c: 90 mg/Day Milademetan | Cohort 9d: 120 mg/Day Milademetan | Cohort 1: 15 mg/Day Milademetan | Cohort 10e: 120 mg/Day Milademetan | Cohort 11e: 200 mg/Day Milademetan | Cohort 12d: 200 mg/Day Milademetan | Cohort 13e: 260 mg/Day Milademetan | Cohort 14e: 340 mg/Day Milademetan | Expansion Cohort: 120 mg/Day Milademetan |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 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 | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 36 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 3 Participants | 4 Participants | 7 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 5 Participants | 0 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 71 Participants | 0 Participants | 0 Participants | 11 Participants | 2 Participants | 2 Participants | 5 Participants | 8 Participants | 5 Participants | 3 Participants | 2 Participants | 2 Participants | 3 Participants | 15 Participants | 3 Participants | 10 Participants |
| Age, Continuous | 59.4 years STANDARD_DEVIATION 11.6 | 69.0 years | 67.0 years | 59.8 years STANDARD_DEVIATION 8.6 | 55.0 years STANDARD_DEVIATION 12.7 | 64.0 years STANDARD_DEVIATION 10.9 | 59.0 years STANDARD_DEVIATION 12 | 63.4 years STANDARD_DEVIATION 12 | 55.8 years STANDARD_DEVIATION 11.1 | 53.0 years STANDARD_DEVIATION 0 | 53.3 years STANDARD_DEVIATION 15.8 | 56.0 years STANDARD_DEVIATION 28.2 | 46.0 years STANDARD_DEVIATION 5.6 | 58.9 years STANDARD_DEVIATION 11.4 | 57.3 years STANDARD_DEVIATION 2.9 | 61.3 years STANDARD_DEVIATION 12.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 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 | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 9 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 90 Participants | 1 Participants | 1 Participants | 12 Participants | 0 Participants | 4 Participants | 9 Participants | 15 Participants | 4 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 16 Participants | 2 Participants | 17 Participants |
| Region of Enrollment United States | 107 participants | 1 participants | 1 participants | 13 participants | 2 participants | 5 participants | 9 participants | 15 participants | 6 participants | 3 participants | 3 participants | 3 participants | 3 participants | 20 participants | 3 participants | 20 participants |
| Sex: Female, Male Female | 53 Participants | 0 Participants | 0 Participants | 7 Participants | 2 Participants | 4 Participants | 4 Participants | 9 Participants | 3 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 8 Participants | 2 Participants | 8 Participants |
| Sex: Female, Male Male | 54 Participants | 1 Participants | 1 Participants | 6 Participants | 0 Participants | 1 Participants | 5 Participants | 6 Participants | 3 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 12 Participants | 1 Participants | 12 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 | EG013 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 1 | 0 / 1 | 3 / 33 | 0 / 2 | 0 / 5 | 0 / 9 | 1 / 15 | 0 / 6 | 0 / 3 | 0 / 3 | 0 / 3 | 3 / 20 | 1 / 3 |
| other Total, other adverse events | 3 / 3 | 1 / 1 | 1 / 1 | 33 / 33 | 2 / 2 | 5 / 5 | 9 / 9 | 15 / 15 | 6 / 6 | 3 / 3 | 3 / 3 | 3 / 3 | 20 / 20 | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 1 | 0 / 1 | 11 / 33 | 1 / 2 | 2 / 5 | 3 / 9 | 2 / 15 | 0 / 6 | 2 / 3 | 0 / 3 | 0 / 3 | 4 / 20 | 1 / 3 |
Outcome results
Primary
Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE
A dose-limiting toxicity (DLT) was defined as any treatment-emergent AE (TEAE) not attributable to the participant's disease or a disease-related processes that occurred during the observation period (Cycle 1) in each dose-level cohort and was Grade 3 or higher according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0, with a few exceptions.
Time frame: Cycle 1, Day 1 to Day 28 (each cycle, 28 days)
Population: Dose-limiting toxicities were assessed in the DLT Evaluable Set in cohorts with available patient data. DLTs were not evaluated in the Expansion Cohort.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Malaise | 0 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Leukopenia | 0 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Neutropenia | 0 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Nausea | 0 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Any TEAE classified as DLT | 0 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Thrombocytopenia | 0 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Vomiting | 0 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 Neutropenia | 0 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 Thrombocytopenia | 0 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Decreased appetite | 0 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 DLT | 0 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Nausea | 0 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Fatigue | 0 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Thrombocytopenia | 0 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Decreased appetite | 0 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Malaise | 0 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 DLT | 0 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Thrombocytopenia | 0 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 DLT | 0 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Leukopenia | 0 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Vomiting | 0 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Fatigue | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Vomiting | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 DLT | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 DLT | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Leukopenia | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Nausea | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Malaise | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Thrombocytopenia | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Leukopenia | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Malaise | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Neutropenia | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Thrombocytopenia | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 Thrombocytopenia | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Fatigue | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Decreased appetite | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Fatigue | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Any TEAE classified as DLT | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 Neutropenia | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Thrombocytopenia | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Vomiting | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 DLT | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Nausea | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Decreased appetite | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 Thrombocytopenia | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 DLT | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Any TEAE classified as DLT | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Leukopenia | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 DLT | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 Neutropenia | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Thrombocytopenia | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Vomiting | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Thrombocytopenia | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Vomiting | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Nausea | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Malaise | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Malaise | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Thrombocytopenia | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Nausea | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Decreased appetite | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Decreased appetite | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Neutropenia | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Fatigue | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Leukopenia | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Fatigue | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 DLT | 0 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Thrombocytopenia | 2 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Thrombocytopenia | 1 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Malaise | 0 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Malaise | 0 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 DLT | 1 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Fatigue | 0 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Decreased appetite | 0 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Fatigue | 0 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Any TEAE classified as DLT | 2 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Vomiting | 0 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Vomiting | 0 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 DLT | 0 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Nausea | 0 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 DLT | 1 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Decreased appetite | 0 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Nausea | 0 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 Neutropenia | 0 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Leukopenia | 0 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Neutropenia | 0 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 Thrombocytopenia | 1 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Leukopenia | 0 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Thrombocytopenia | 0 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Decreased appetite | 0 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Vomiting | 0 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Thrombocytopenia | 0 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 Thrombocytopenia | 1 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Thrombocytopenia | 1 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Malaise | 0 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Fatigue | 0 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 Neutropenia | 0 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Leukopenia | 0 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Thrombocytopenia | 0 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Any TEAE classified as DLT | 1 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Malaise | 0 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Fatigue | 0 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Nausea | 0 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Decreased appetite | 0 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Nausea | 0 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Neutropenia | 0 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 DLT | 0 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Vomiting | 0 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Leukopenia | 0 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 DLT | 0 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 DLT | 1 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 DLT | 0 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 DLT | 1 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 Neutropenia | 1 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Vomiting | 1 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Vomiting | 1 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Thrombocytopenia | 0 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Thrombocytopenia | 1 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Any TEAE classified as DLT | 2 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Neutropenia | 1 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Decreased appetite | 1 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Fatigue | 0 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Malaise | 0 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 Thrombocytopenia | 0 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Leukopenia | 1 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Leukopenia | 1 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Fatigue | 0 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Decreased appetite | 1 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Nausea | 1 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 DLT | 1 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Nausea | 1 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Malaise | 0 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Thrombocytopenia | 1 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Any TEAE classified as DLT | 1 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Thrombocytopenia | 1 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 Thrombocytopenia | 0 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Malaise | 0 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Malaise | 0 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Decreased appetite | 0 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 DLT | 0 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 DLT | 1 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 DLT | 0 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Thrombocytopenia | 1 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Thrombocytopenia | 0 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Leukopenia | 0 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Leukopenia | 0 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Neutropenia | 0 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 Neutropenia | 0 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Nausea | 0 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Nausea | 0 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Vomiting | 0 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Vomiting | 0 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Fatigue | 0 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Fatigue | 0 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Decreased appetite | 0 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Vomiting | 0 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Thrombocytopenia | 0 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 DLT | 0 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 DLT | 0 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Nausea | 0 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Fatigue | 0 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Decreased appetite | 0 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Leukopenia | 0 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Leukopenia | 0 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Malaise | 0 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 Thrombocytopenia | 0 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Malaise | 0 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Neutropenia | 0 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Fatigue | 0 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Thrombocytopenia | 0 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Decreased appetite | 0 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 Neutropenia | 0 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Vomiting | 0 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 DLT | 0 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Any TEAE classified as DLT | 0 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Nausea | 0 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Thrombocytopenia | 0 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Neutropenia | 0 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Nausea | 0 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Vomiting | 0 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 DLT | 0 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 Neutropenia | 0 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Malaise | 1 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 DLT | 0 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Thrombocytopenia | 0 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Nausea | 0 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 Thrombocytopenia | 0 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Vomiting | 0 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Fatigue | 1 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Fatigue | 1 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Any TEAE classified as DLT | 1 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Leukopenia | 0 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Thrombocytopenia | 0 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Thrombocytopenia | 0 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Decreased appetite | 0 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Leukopenia | 0 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Decreased appetite | 0 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 DLT | 1 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Malaise | 1 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Malaise | 0 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 DLT | 0 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Malaise | 0 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Any TEAE classified as DLT | 0 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Neutropenia | 0 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Leukopenia | 0 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Fatigue | 0 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Thrombocytopenia | 0 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Vomiting | 0 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Decreased appetite | 0 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Decreased appetite | 0 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 DLT | 0 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 Neutropenia | 0 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Nausea | 0 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 DLT | 0 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Fatigue | 0 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Thrombocytopenia | 0 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 Thrombocytopenia | 0 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Nausea | 0 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Vomiting | 0 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Leukopenia | 0 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Thrombocytopenia | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Thrombocytopenia | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Leukopenia | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 Thrombocytopenia | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Leukopenia | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Thrombocytopenia | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Neutropenia | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 Neutropenia | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 DLT | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Decreased appetite | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Nausea | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 DLT | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Nausea | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Vomiting | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Any TEAE classified as DLT | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Vomiting | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Decreased appetite | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 DLT | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Fatigue | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Malaise | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Fatigue | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Malaise | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Thrombocytopenia | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Vomiting | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Vomiting | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Any TEAE classified as DLT | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Leukopenia | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Nausea | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 Neutropenia | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Thrombocytopenia | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 DLT | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Neutropenia | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Fatigue | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Malaise | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Decreased appetite | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Malaise | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Thrombocytopenia | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Fatigue | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Leukopenia | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Thrombocytopenia | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 Thrombocytopenia | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 DLT | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Nausea | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Decreased appetite | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 DLT | 0 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Fatigue | 0 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Nausea | 0 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Leukopenia | 0 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Thrombocytopenia | 0 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Vomiting | 0 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Malaise | 0 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Any TEAE classified as DLT | 0 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Thrombocytopenia | 0 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Neutropenia | 0 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Leukopenia | 0 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 DLT | 0 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Fatigue | 0 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Decreased appetite | 0 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 Neutropenia | 0 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 DLT | 0 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Decreased appetite | 0 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Nausea | 0 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Vomiting | 0 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Thrombocytopenia | 0 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Malaise | 0 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 Thrombocytopenia | 0 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 DLT | 0 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Malaise | 0 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 DLT | 0 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Neutropenia | 0 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 DLT | 0 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Thrombocytopenia | 0 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Fatigue | 0 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Decreased appetite | 0 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 Thrombocytopenia | 0 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Malaise | 0 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Leukopenia | 0 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Thrombocytopenia | 1 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Thrombocytopenia | 1 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Fatigue | 0 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Nausea | 0 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Vomiting | 0 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 2 Leukopenia | 0 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 DLT | 1 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 4 Neutropenia | 0 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Nausea | 0 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Vomiting | 0 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Grade 3 Decreased appetite | 0 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Any TEAE classified as DLT | 1 Participants |
Primary
Number of Participants With Melanoma and Diffuse Large B Cell Lymphoma Who Achieved Objective Response
Tumor response was assessed using RECIST Version 1.1 (in solid tumor participants with measurable disease) or treatment response using the revised International Working Group criteria 7 (in participants with lymphoma). For RECIST, complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. Objective response rate (ORR) was the sum of CR and PR rates.
Time frame: Screening up to Cycle 3 and beyond, Day 1 (each cycle, 28 days)
Population: Objective response was assessed in the Dose Expansion cohort of the Full Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Melanoma and Diffuse Large B Cell Lymphoma Who Achieved Objective Response | Complete response | 0 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Melanoma and Diffuse Large B Cell Lymphoma Who Achieved Objective Response | Partial response | 1 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Melanoma and Diffuse Large B Cell Lymphoma Who Achieved Objective Response | Stable disease | 8 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Melanoma and Diffuse Large B Cell Lymphoma Who Achieved Objective Response | Progressive disease | 5 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Melanoma and Diffuse Large B Cell Lymphoma Who Achieved Objective Response | Inevaluable | 6 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Melanoma and Diffuse Large B Cell Lymphoma Who Achieved Objective Response | Objective response rate (CR + PR) | 1 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan
A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that emerged during the treatment period (from first dose date until 30 days after the last dosing date), having been absent at pretreatment; or reemerged during treatment, having been present at baseline, but stopped prior to treatment; or worsened in severity after starting treatment relative to the pretreatment state, when the AE was continuous.
Time frame: Screening until end of treatment visit, up to approximately 7 years 2 months
Population: Treatment-emergent adverse events (TEAEs) were assessed in the Safety Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Vomiting | 1 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Leukopenia | 0 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Headache | 0 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Neutropenia | 0 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Dyspnea | 1 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Anemia | 1 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Nausea | 1 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Aspartate aminotransferase increased | 2 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Diarrhea | 0 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Constipation | 1 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Any TEAE | 3 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Cough | 1 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Decreased appetite | 1 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Thrombocytopenia | 0 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Fatigue | 0 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Edema peripheral | 2 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Lymphopenia | 0 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Abdominal pain | 1 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Dysgeusia | 1 Participants |
| Cohort 1: 15 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Pyrexia | 1 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Decreased appetite | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Vomiting | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Constipation | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Any TEAE | 1 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Fatigue | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Aspartate aminotransferase increased | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Headache | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Lymphopenia | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Nausea | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Anemia | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Pyrexia | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Dysgeusia | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Neutropenia | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Edema peripheral | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Leukopenia | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Dyspnea | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Diarrhea | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Thrombocytopenia | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Cough | 0 Participants |
| Cohort 2: 30 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Abdominal pain | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Edema peripheral | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Lymphopenia | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Anemia | 1 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Fatigue | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Nausea | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Any TEAE | 1 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Neutropenia | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Leukopenia | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Abdominal pain | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Diarrhea | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Vomiting | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Aspartate aminotransferase increased | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Headache | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Constipation | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Dysgeusia | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Cough | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Dyspnea | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Decreased appetite | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Thrombocytopenia | 0 Participants |
| Cohort 3: 60 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Pyrexia | 0 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Cough | 4 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Nausea | 22 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Abdominal pain | 5 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Any TEAE | 33 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Diarrhea | 16 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Dyspnea | 5 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Pyrexia | 2 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Anemia | 16 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Leukopenia | 9 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Decreased appetite | 10 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Fatigue | 18 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Lymphopenia | 2 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Thrombocytopenia | 25 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Dysgeusia | 7 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Headache | 5 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Vomiting | 10 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Edema peripheral | 4 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Neutropenia | 9 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Aspartate aminotransferase increased | 2 Participants |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Constipation | 7 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Edema peripheral | 0 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Any TEAE | 2 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Nausea | 2 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Diarrhea | 1 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Vomiting | 2 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Abdominal pain | 0 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Thrombocytopenia | 1 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Lymphopenia | 0 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Headache | 1 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Pyrexia | 0 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Decreased appetite | 2 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Dyspnea | 1 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Cough | 0 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Dysgeusia | 1 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Aspartate aminotransferase increased | 0 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Constipation | 1 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Anemia | 1 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Leukopenia | 1 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Neutropenia | 1 Participants |
| Cohort 5: 240 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Fatigue | 2 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Dyspnea | 1 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Decreased appetite | 5 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Thrombocytopenia | 4 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Fatigue | 4 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Edema peripheral | 0 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Any TEAE | 5 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Leukopenia | 5 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Lymphopenia | 0 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Anemia | 3 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Dysgeusia | 1 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Headache | 1 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Diarrhea | 3 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Aspartate aminotransferase increased | 0 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Vomiting | 3 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Constipation | 0 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Cough | 2 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Nausea | 5 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Pyrexia | 0 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Neutropenia | 4 Participants |
| Cohort 6: 160 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Abdominal pain | 2 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Neutropenia | 4 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Abdominal pain | 1 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Decreased appetite | 5 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Headache | 2 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Thrombocytopenia | 5 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Cough | 3 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Any TEAE | 9 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Diarrhea | 4 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Lymphopenia | 1 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Nausea | 7 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Leukopenia | 5 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Constipation | 4 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Edema peripheral | 1 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Aspartate aminotransferase increased | 0 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Dyspnea | 2 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Anemia | 4 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Pyrexia | 2 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Vomiting | 2 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Dysgeusia | 3 Participants |
| Cohort 7b: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Fatigue | 4 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Neutropenia | 6 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Edema peripheral | 5 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Cough | 6 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Thrombocytopenia | 13 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Fatigue | 10 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Pyrexia | 2 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Decreased appetite | 7 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Abdominal pain | 4 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Dyspnea | 5 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Constipation | 5 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Dysgeusia | 3 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Headache | 4 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Vomiting | 4 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Aspartate aminotransferase increased | 3 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Diarrhea | 7 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Anemia | 9 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Any TEAE | 15 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Leukopenia | 9 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Nausea | 13 Participants |
| Cohort 8c: 90 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Lymphopenia | 3 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Headache | 2 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Abdominal pain | 0 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Decreased appetite | 1 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Leukopenia | 1 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Constipation | 2 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Pyrexia | 1 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Fatigue | 4 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Cough | 1 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Vomiting | 2 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Dyspnea | 3 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Dysgeusia | 0 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Neutropenia | 1 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Any TEAE | 6 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Edema peripheral | 0 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Lymphopenia | 1 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Nausea | 4 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Anemia | 2 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Thrombocytopenia | 2 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Diarrhea | 0 Participants |
| Cohort 9d: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Aspartate aminotransferase increased | 1 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Anemia | 0 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Diarrhea | 1 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Leukopenia | 1 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Thrombocytopenia | 1 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Fatigue | 2 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Constipation | 1 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Decreased appetite | 1 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Cough | 0 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Pyrexia | 0 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Neutropenia | 0 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Abdominal pain | 1 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Dysgeusia | 0 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Dyspnea | 0 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Any TEAE | 3 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Vomiting | 1 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Headache | 1 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Lymphopenia | 1 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Edema peripheral | 0 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Aspartate aminotransferase increased | 0 Participants |
| Cohort 10e: 120 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Nausea | 1 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Anemia | 2 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Lymphopenia | 2 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Cough | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Nausea | 2 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Headache | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Pyrexia | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Thrombocytopenia | 1 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Fatigue | 1 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Edema peripheral | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Aspartate aminotransferase increased | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Constipation | 1 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Abdominal pain | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Decreased appetite | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Dysgeusia | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Diarrhea | 1 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Neutropenia | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Any TEAE | 3 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Dyspnea | 0 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Vomiting | 1 Participants |
| Cohort 11e: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Leukopenia | 1 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Diarrhea | 1 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Dyspnea | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Constipation | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Cough | 1 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Anemia | 2 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Fatigue | 2 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Edema peripheral | 1 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Dysgeusia | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Vomiting | 1 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Headache | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Pyrexia | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Abdominal pain | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Aspartate aminotransferase increased | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Nausea | 3 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Leukopenia | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Thrombocytopenia | 2 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Neutropenia | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Lymphopenia | 0 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Any TEAE | 3 Participants |
| Cohort 12d: 200 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Decreased appetite | 0 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Decreased appetite | 8 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Lymphopenia | 4 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Any TEAE | 20 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Dyspnea | 4 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Thrombocytopenia | 11 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Dysgeusia | 4 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Anemia | 5 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Vomiting | 11 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Edema peripheral | 3 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Fatigue | 10 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Pyrexia | 3 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Diarrhea | 9 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Cough | 3 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Neutropenia | 4 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Headache | 2 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Leukopenia | 7 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Abdominal pain | 3 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Constipation | 5 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Nausea | 16 Participants |
| Cohort 13e: 260 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Aspartate aminotransferase increased | 3 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Edema peripheral | 0 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Constipation | 0 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Fatigue | 2 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Vomiting | 2 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Leukopenia | 0 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Lymphopenia | 0 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Thrombocytopenia | 2 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Neutropenia | 0 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Any TEAE | 3 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Aspartate aminotransferase increased | 1 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Diarrhea | 2 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Headache | 1 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Anemia | 0 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Decreased appetite | 2 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Dyspnea | 0 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Dysgeusia | 0 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Pyrexia | 0 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Cough | 0 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Nausea | 2 Participants |
| Cohort 14e: 340 mg/Day Milademetan | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Abdominal pain | 1 Participants |
Secondary
Mean Fold Change From Baseline in Serum MIC-1 Levels in Participants Receiving Milademetan
Mean fold change in macrophage inhibitory cytokine-1 (MIC-1) levels in serum from baseline are summarized using descriptive statistics by cohort.
Time frame: Cycle 1, Day 15 and Cycle 1, Days 18 to 21 (each cycle is 28 days)
Population: Serum MIC-1 levels were assessed in the Biomarker Analysis Set in participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 15 mg/Day Milademetan | Mean Fold Change From Baseline in Serum MIC-1 Levels in Participants Receiving Milademetan | Cycle 1, Day 15 | 1.65 fold change | Standard Deviation 0.5 |
| Cohort 1: 15 mg/Day Milademetan | Mean Fold Change From Baseline in Serum MIC-1 Levels in Participants Receiving Milademetan | Cycle 1, Days 18 to 21 | 1.98 fold change | Standard Deviation 1.1 |
| Cohort 2: 30 mg/Day Milademetan | Mean Fold Change From Baseline in Serum MIC-1 Levels in Participants Receiving Milademetan | Cycle 1, Days 18 to 21 | 1.69 fold change | — |
| Cohort 2: 30 mg/Day Milademetan | Mean Fold Change From Baseline in Serum MIC-1 Levels in Participants Receiving Milademetan | Cycle 1, Day 15 | 2.39 fold change | — |
| Cohort 3: 60 mg/Day Milademetan | Mean Fold Change From Baseline in Serum MIC-1 Levels in Participants Receiving Milademetan | Cycle 1, Days 18 to 21 | 2.00 fold change | — |
| Cohort 3: 60 mg/Day Milademetan | Mean Fold Change From Baseline in Serum MIC-1 Levels in Participants Receiving Milademetan | Cycle 1, Day 15 | 2.05 fold change | — |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Mean Fold Change From Baseline in Serum MIC-1 Levels in Participants Receiving Milademetan | Cycle 1, Day 15 | 6.13 fold change | Standard Deviation 3.6 |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Mean Fold Change From Baseline in Serum MIC-1 Levels in Participants Receiving Milademetan | Cycle 1, Days 18 to 21 | 6.17 fold change | Standard Deviation 3.3 |
| Cohort 5: 240 mg/Day Milademetan | Mean Fold Change From Baseline in Serum MIC-1 Levels in Participants Receiving Milademetan | Cycle 1, Day 15 | 31.03 fold change | — |
| Cohort 5: 240 mg/Day Milademetan | Mean Fold Change From Baseline in Serum MIC-1 Levels in Participants Receiving Milademetan | Cycle 1, Days 18 to 21 | 47.40 fold change | — |
| Cohort 6: 160 mg/Day Milademetan | Mean Fold Change From Baseline in Serum MIC-1 Levels in Participants Receiving Milademetan | Cycle 1, Day 15 | 18.59 fold change | Standard Deviation 9.5 |
| Cohort 6: 160 mg/Day Milademetan | Mean Fold Change From Baseline in Serum MIC-1 Levels in Participants Receiving Milademetan | Cycle 1, Days 18 to 21 | 15.49 fold change | Standard Deviation 10 |
| Cohort 7b: 90 mg/Day Milademetan | Mean Fold Change From Baseline in Serum MIC-1 Levels in Participants Receiving Milademetan | Cycle 1, Day 15 | 5.80 fold change | Standard Deviation 2.3 |
| Cohort 7b: 90 mg/Day Milademetan | Mean Fold Change From Baseline in Serum MIC-1 Levels in Participants Receiving Milademetan | Cycle 1, Days 18 to 21 | 4.99 fold change | Standard Deviation 1.6 |
| Cohort 8c: 90 mg/Day Milademetan | Mean Fold Change From Baseline in Serum MIC-1 Levels in Participants Receiving Milademetan | Cycle 1, Day 15 | 8.71 fold change | Standard Deviation 5.8 |
| Cohort 8c: 90 mg/Day Milademetan | Mean Fold Change From Baseline in Serum MIC-1 Levels in Participants Receiving Milademetan | Cycle 1, Days 18 to 21 | 8.32 fold change | Standard Deviation 4.9 |
| Cohort 9d: 120 mg/Day Milademetan | Mean Fold Change From Baseline in Serum MIC-1 Levels in Participants Receiving Milademetan | Cycle 1, Day 15 | 1.21 fold change | Standard Deviation 0.2 |
| Cohort 10e: 120 mg/Day Milademetan | Mean Fold Change From Baseline in Serum MIC-1 Levels in Participants Receiving Milademetan | Cycle 1, Day 15 | 1.01 fold change | Standard Deviation 0.2 |
| Cohort 11e: 200 mg/Day Milademetan | Mean Fold Change From Baseline in Serum MIC-1 Levels in Participants Receiving Milademetan | Cycle 1, Day 15 | 1.02 fold change | Standard Deviation 0.3 |
| Cohort 12d: 200 mg/Day Milademetan | Mean Fold Change From Baseline in Serum MIC-1 Levels in Participants Receiving Milademetan | Cycle 1, Day 15 | 1.35 fold change | Standard Deviation 0.1 |
| Cohort 13e: 260 mg/Day Milademetan | Mean Fold Change From Baseline in Serum MIC-1 Levels in Participants Receiving Milademetan | Cycle 1, Days 18 to 21 | 21.50 fold change | Standard Deviation 14.6 |
| Cohort 13e: 260 mg/Day Milademetan | Mean Fold Change From Baseline in Serum MIC-1 Levels in Participants Receiving Milademetan | Cycle 1, Day 15 | 2.85 fold change | Standard Deviation 6.4 |
| Cohort 14e: 340 mg/Day Milademetan | Mean Fold Change From Baseline in Serum MIC-1 Levels in Participants Receiving Milademetan | Cycle 1, Day 15 | 1.76 fold change | Standard Deviation 1.6 |
| Expansion Cohort: 120 mg/Day Milademetan | Mean Fold Change From Baseline in Serum MIC-1 Levels in Participants Receiving Milademetan | Cycle 1, Days 18 to 21 | 5.48 fold change | Standard Deviation 3.4 |
| Expansion Cohort: 120 mg/Day Milademetan | Mean Fold Change From Baseline in Serum MIC-1 Levels in Participants Receiving Milademetan | Cycle 1, Day 15 | 4.90 fold change | Standard Deviation 3.4 |
Secondary
Pharmacokinetic Parameter Apparent Clearance (CL/F) of Milademetan In Participants Receiving Milademetan
Plasma pharmacokinetic parameters of DS-3032a were calculated using noncompartmental methods.
Time frame: Escalation:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,6-8 hours(h);Cycle 2,Day 1 Predose,1,3,6-8h,30 days after last dose; Expansion:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,4,6,8h;Cycle 2,Day 1 Predose,1,2,3,4,6,8h and Day 2 (each cycle, 28 days)
Population: Pharmacokinetic parameters were assessed in participants with available data in the Pharmacokinetic Analysis Set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: 15 mg/Day Milademetan | Pharmacokinetic Parameter Apparent Clearance (CL/F) of Milademetan In Participants Receiving Milademetan | 12.7 L/h |
| Cohort 3: 60 mg/Day Milademetan | Pharmacokinetic Parameter Apparent Clearance (CL/F) of Milademetan In Participants Receiving Milademetan | 18.5 L/h |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Pharmacokinetic Parameter Apparent Clearance (CL/F) of Milademetan In Participants Receiving Milademetan | 31.6 L/h |
| Cohort 7b: 90 mg/Day Milademetan | Pharmacokinetic Parameter Apparent Clearance (CL/F) of Milademetan In Participants Receiving Milademetan | 7.2 L/h |
| Cohort 13e: 260 mg/Day Milademetan | Pharmacokinetic Parameter Apparent Clearance (CL/F) of Milademetan In Participants Receiving Milademetan | 17.8 L/h |
| Cohort 14e: 340 mg/Day Milademetan | Pharmacokinetic Parameter Apparent Clearance (CL/F) of Milademetan In Participants Receiving Milademetan | 12.1 L/h |
Secondary
Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan
Area under the curve from time 0 to 24 hours (AUC0-24), time 0 to infinity (AUCinf), and to the last measurable concentration (AUClast). Plasma pharmacokinetic parameters of DS-3032a were calculated using noncompartmental methods.
Time frame: Escalation:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,6-8 hours(h);Cycle 2,Day 1 Predose,1,3,6-8h,30 days after last dose; Expansion:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,4,6,8h;Cycle 2,Day 1 Predose,1,2,3,4,6,8h and Day 2 (each cycle, 28 days)
Population: Pharmacokinetic parameters were assessed in participants with available data in the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 15 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUClast | 927.1 ng*h/mL | Standard Deviation 73 |
| Cohort 1: 15 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUC0-24 | 934.0 ng*h/mL | Standard Deviation 58.9 |
| Cohort 1: 15 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUCinf | 1182.2 ng*h/mL | — |
| Cohort 2: 30 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUClast | 1907.2 ng*h/mL | — |
| Cohort 2: 30 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUC0-24 | 2211.0 ng*h/mL | — |
| Cohort 3: 60 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUC0-24 | 2930.4 ng*h/mL | — |
| Cohort 3: 60 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUCinf | 3248.4 ng*h/mL | — |
| Cohort 3: 60 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUClast | 2864.4 ng*h/mL | — |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUC0-24 | 7421.2 ng*h/mL | Standard Deviation 3183.6 |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUCinf | 3799.4 ng*h/mL | — |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUClast | 7375.7 ng*h/mL | Standard Deviation 2987.9 |
| Cohort 5: 240 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUClast | 20547.1 ng*h/mL | Standard Deviation 9807.2 |
| Cohort 5: 240 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUC0-24 | 21386.7 ng*h/mL | Standard Deviation 8068.1 |
| Cohort 6: 160 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUClast | 18190.2 ng*h/mL | Standard Deviation 6652.6 |
| Cohort 6: 160 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUC0-24 | 17747.4 ng*h/mL | Standard Deviation 7912.1 |
| Cohort 7b: 90 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUC0-24 | 7828.7 ng*h/mL | Standard Deviation 4229.9 |
| Cohort 7b: 90 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUClast | 7243.8 ng*h/mL | Standard Deviation 4546 |
| Cohort 7b: 90 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUCinf | 12586.1 ng*h/mL | — |
| Cohort 8c: 90 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUClast | 6798.5 ng*h/mL | Standard Deviation 2655.4 |
| Cohort 8c: 90 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUC0-24 | 7080.0 ng*h/mL | Standard Deviation 2891.7 |
| Cohort 9d: 120 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUC0-24 | 6943.6 ng*h/mL | Standard Deviation 1994.2 |
| Cohort 9d: 120 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUClast | 7334.6 ng*h/mL | Standard Deviation 2486.1 |
| Cohort 10e: 120 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUC0-24 | 9752.2 ng*h/mL | Standard Deviation 3532 |
| Cohort 10e: 120 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUClast | 9715.2 ng*h/mL | Standard Deviation 3532.3 |
| Cohort 11e: 200 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUClast | 12059.1 ng*h/mL | Standard Deviation 6183.5 |
| Cohort 11e: 200 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUC0-24 | 15928.8 ng*h/mL | Standard Deviation 1235.9 |
| Cohort 12d: 200 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUC0-24 | 12602.8 ng*h/mL | Standard Deviation 8527.7 |
| Cohort 12d: 200 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUClast | 11928.4 ng*h/mL | Standard Deviation 5518.5 |
| Cohort 13e: 260 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUClast | 19619.9 ng*h/mL | Standard Deviation 6897.2 |
| Cohort 13e: 260 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUCinf | 18925.3 ng*h/mL | Standard Deviation 12784.2 |
| Cohort 13e: 260 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUC0-24 | 20006.9 ng*h/mL | Standard Deviation 7204.6 |
| Cohort 14e: 340 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUCinf | 28031.5 ng*h/mL | — |
| Cohort 14e: 340 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUC0-24 | 39118.2 ng*h/mL | Standard Deviation 16317.6 |
| Cohort 14e: 340 mg/Day Milademetan | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | AUClast | 24701.2 ng*h/mL | Standard Deviation 21198 |
Secondary
Pharmacokinetic Parameter Elimination Terminal Half Life Half-Life (T1/2) of Milademetan In Participants Receiving Milademetan
Plasma pharmacokinetic parameters of DS-3032a were calculated using noncompartmental methods.
Time frame: Escalation:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,6-8 hours(h);Cycle 2,Day 1 Predose,1,3,6-8h,30 days after last dose; Expansion:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,4,6,8h;Cycle 2,Day 1 Predose,1,2,3,4,6,8h and Day 2 (each cycle, 28 days)
Population: Pharmacokinetic parameters were assessed in participants with available data in the Pharmacokinetic Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 15 mg/Day Milademetan | Pharmacokinetic Parameter Elimination Terminal Half Life Half-Life (T1/2) of Milademetan In Participants Receiving Milademetan | 13.4 hours | Standard Deviation 3.7 |
| Cohort 2: 30 mg/Day Milademetan | Pharmacokinetic Parameter Elimination Terminal Half Life Half-Life (T1/2) of Milademetan In Participants Receiving Milademetan | 9.3 hours | — |
| Cohort 3: 60 mg/Day Milademetan | Pharmacokinetic Parameter Elimination Terminal Half Life Half-Life (T1/2) of Milademetan In Participants Receiving Milademetan | 6.7 hours | — |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Pharmacokinetic Parameter Elimination Terminal Half Life Half-Life (T1/2) of Milademetan In Participants Receiving Milademetan | 12.8 hours | Standard Deviation 2.9 |
| Cohort 5: 240 mg/Day Milademetan | Pharmacokinetic Parameter Elimination Terminal Half Life Half-Life (T1/2) of Milademetan In Participants Receiving Milademetan | 14.5 hours | Standard Deviation 0.5 |
| Cohort 6: 160 mg/Day Milademetan | Pharmacokinetic Parameter Elimination Terminal Half Life Half-Life (T1/2) of Milademetan In Participants Receiving Milademetan | 13.1 hours | Standard Deviation 3.8 |
| Cohort 7b: 90 mg/Day Milademetan | Pharmacokinetic Parameter Elimination Terminal Half Life Half-Life (T1/2) of Milademetan In Participants Receiving Milademetan | 17.6 hours | Standard Deviation 13.6 |
| Cohort 8c: 90 mg/Day Milademetan | Pharmacokinetic Parameter Elimination Terminal Half Life Half-Life (T1/2) of Milademetan In Participants Receiving Milademetan | 12.4 hours | Standard Deviation 2.3 |
| Cohort 9d: 120 mg/Day Milademetan | Pharmacokinetic Parameter Elimination Terminal Half Life Half-Life (T1/2) of Milademetan In Participants Receiving Milademetan | 13.6 hours | Standard Deviation 1.6 |
| Cohort 10e: 120 mg/Day Milademetan | Pharmacokinetic Parameter Elimination Terminal Half Life Half-Life (T1/2) of Milademetan In Participants Receiving Milademetan | 13.9 hours | Standard Deviation 0.6 |
| Cohort 11e: 200 mg/Day Milademetan | Pharmacokinetic Parameter Elimination Terminal Half Life Half-Life (T1/2) of Milademetan In Participants Receiving Milademetan | 13.4 hours | Standard Deviation 4.7 |
| Cohort 12d: 200 mg/Day Milademetan | Pharmacokinetic Parameter Elimination Terminal Half Life Half-Life (T1/2) of Milademetan In Participants Receiving Milademetan | 13.1 hours | Standard Deviation 4.2 |
| Cohort 13e: 260 mg/Day Milademetan | Pharmacokinetic Parameter Elimination Terminal Half Life Half-Life (T1/2) of Milademetan In Participants Receiving Milademetan | 10.9 hours | Standard Deviation 3.9 |
| Cohort 14e: 340 mg/Day Milademetan | Pharmacokinetic Parameter Elimination Terminal Half Life Half-Life (T1/2) of Milademetan In Participants Receiving Milademetan | 7.2 hours | Standard Deviation 4.9 |
Secondary
Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of Milademetan In Participants Receiving Milademetan
Plasma pharmacokinetic parameters of DS-3032a were calculated using noncompartmental methods.
Time frame: Escalation:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,6-8 hours(h);Cycle 2,Day 1 Predose,1,3,6-8h,30 days after last dose; Expansion:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,4,6,8h;Cycle 2,Day 1 Predose,1,2,3,4,6,8h and Day 2 (each cycle, 28 days)
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 15 mg/Day Milademetan | Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of Milademetan In Participants Receiving Milademetan | 83.1 ng/mL | Standard Deviation 23.8 |
| Cohort 2: 30 mg/Day Milademetan | Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of Milademetan In Participants Receiving Milademetan | 198.0 ng/mL | — |
| Cohort 3: 60 mg/Day Milademetan | Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of Milademetan In Participants Receiving Milademetan | 310.0 ng/mL | — |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of Milademetan In Participants Receiving Milademetan | 551.7 ng/mL | Standard Deviation 199.5 |
| Cohort 5: 240 mg/Day Milademetan | Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of Milademetan In Participants Receiving Milademetan | 1525.0 ng/mL | Standard Deviation 700 |
| Cohort 6: 160 mg/Day Milademetan | Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of Milademetan In Participants Receiving Milademetan | 1301.8 ng/mL | Standard Deviation 534.6 |
| Cohort 7b: 90 mg/Day Milademetan | Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of Milademetan In Participants Receiving Milademetan | 567.7 ng/mL | Standard Deviation 341.8 |
| Cohort 8c: 90 mg/Day Milademetan | Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of Milademetan In Participants Receiving Milademetan | 527.7 ng/mL | Standard Deviation 211.7 |
| Cohort 9d: 120 mg/Day Milademetan | Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of Milademetan In Participants Receiving Milademetan | 622.0 ng/mL | Standard Deviation 182.8 |
| Cohort 10e: 120 mg/Day Milademetan | Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of Milademetan In Participants Receiving Milademetan | 757.3 ng/mL | Standard Deviation 298.6 |
| Cohort 11e: 200 mg/Day Milademetan | Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of Milademetan In Participants Receiving Milademetan | 899.3 ng/mL | Standard Deviation 466 |
| Cohort 12d: 200 mg/Day Milademetan | Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of Milademetan In Participants Receiving Milademetan | 978.0 ng/mL | Standard Deviation 572.6 |
| Cohort 13e: 260 mg/Day Milademetan | Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of Milademetan In Participants Receiving Milademetan | 1625.4 ng/mL | Standard Deviation 587.9 |
| Cohort 14e: 340 mg/Day Milademetan | Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of Milademetan In Participants Receiving Milademetan | 2649.7 ng/mL | Standard Deviation 2160.6 |
Secondary
Pharmacokinetic Parameter Time to Reach Maximum Plasma Concentration (Tmax) of Milademetan In Participants Receiving Milademetan
Plasma pharmacokinetic parameters of DS-3032a were calculated using noncompartmental methods.
Time frame: Escalation:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,6-8 hours(h);Cycle 2,Day 1 Predose,1,3,6-8h,30 days after last dose; Expansion:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,4,6,8h;Cycle 2,Day 1 Predose,1,2,3,4,6,8h and Day 2 (each cycle, 28 days)
Population: Pharmacokinetic parameters were assessed in participants with available data in the Pharmacokinetic Analysis Set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: 15 mg/Day Milademetan | Pharmacokinetic Parameter Time to Reach Maximum Plasma Concentration (Tmax) of Milademetan In Participants Receiving Milademetan | 13.8 hours |
| Cohort 2: 30 mg/Day Milademetan | Pharmacokinetic Parameter Time to Reach Maximum Plasma Concentration (Tmax) of Milademetan In Participants Receiving Milademetan | 9.3 hours |
| Cohort 3: 60 mg/Day Milademetan | Pharmacokinetic Parameter Time to Reach Maximum Plasma Concentration (Tmax) of Milademetan In Participants Receiving Milademetan | 6.7 hours |
| Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Pharmacokinetic Parameter Time to Reach Maximum Plasma Concentration (Tmax) of Milademetan In Participants Receiving Milademetan | 12.9 hours |
| Cohort 5: 240 mg/Day Milademetan | Pharmacokinetic Parameter Time to Reach Maximum Plasma Concentration (Tmax) of Milademetan In Participants Receiving Milademetan | 14.5 hours |
| Cohort 6: 160 mg/Day Milademetan | Pharmacokinetic Parameter Time to Reach Maximum Plasma Concentration (Tmax) of Milademetan In Participants Receiving Milademetan | 13.0 hours |
| Cohort 7b: 90 mg/Day Milademetan | Pharmacokinetic Parameter Time to Reach Maximum Plasma Concentration (Tmax) of Milademetan In Participants Receiving Milademetan | 12.8 hours |
| Cohort 8c: 90 mg/Day Milademetan | Pharmacokinetic Parameter Time to Reach Maximum Plasma Concentration (Tmax) of Milademetan In Participants Receiving Milademetan | 12.1 hours |
| Cohort 9d: 120 mg/Day Milademetan | Pharmacokinetic Parameter Time to Reach Maximum Plasma Concentration (Tmax) of Milademetan In Participants Receiving Milademetan | 13.0 hours |
| Cohort 10e: 120 mg/Day Milademetan | Pharmacokinetic Parameter Time to Reach Maximum Plasma Concentration (Tmax) of Milademetan In Participants Receiving Milademetan | 13.8 hours |
| Cohort 11e: 200 mg/Day Milademetan | Pharmacokinetic Parameter Time to Reach Maximum Plasma Concentration (Tmax) of Milademetan In Participants Receiving Milademetan | 13.4 hours |
| Cohort 12d: 200 mg/Day Milademetan | Pharmacokinetic Parameter Time to Reach Maximum Plasma Concentration (Tmax) of Milademetan In Participants Receiving Milademetan | 13.1 hours |
| Cohort 13e: 260 mg/Day Milademetan | Pharmacokinetic Parameter Time to Reach Maximum Plasma Concentration (Tmax) of Milademetan In Participants Receiving Milademetan | 11.7 hours |
| Cohort 14e: 340 mg/Day Milademetan | Pharmacokinetic Parameter Time to Reach Maximum Plasma Concentration (Tmax) of Milademetan In Participants Receiving Milademetan | 7.2 hours |