Advanced Solid TumorPhase 1NCT01877382

A Multiple Ascending Dose Study of Milademetan in Subjects With Advanced Solid Tumors or Lymphomas

A Phase 1 study testing Milademetan in people with Advanced Solid Tumor and Lymphoma, run by Daiichi Sankyo at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Advanced Solid Tumor, Lymphoma
What is being tested?: Milademetan
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 107 participants
Where: 5 sitesUnited States
Study dates: 11 Jul 2013to 3 Dec 2020
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Show all 26Show fewer

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)

Who cannot join

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.

Show all 17Show fewer

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.

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

United States5 sites

Karmanos Cancer Institute
Detroit, Michigan, 48201
UT MD Anderson Cancer Center
Houston, Texas, 77030
Tennessee Oncology
Nashville, Tennessee, 37203
Columbia University College of Physicians and Surgeons
New York, New York, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, 10065

Other trials in United States

About this study

Official title: A Phase 1 Multiple Ascending Dose Study of Milademetan in Subjects 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.

Conditions: Advanced Solid Tumor, Lymphoma
Being tested: Milademetan
Medical subject headings: Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MilademetanDrug
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.
MilademetanDrug
Milademetan will be administered as a single oral capsule or as a combination of multiple oral capsules containing 5, 20, 80, and/or 200 mg. An alternate combination of 30 and/or 100 mg capsules of milademetan may be utilized.

Study groups in NCT01877382
Study group	Role	What they receive
Part 1, Milademetan Alone	Experimental	Participants receive milademetan alone with different dose schedules. Receives: Drug: Milademetan
Part 2, Milademetan Alone	Experimental	Participants with advanced melanoma and diffuse large B cell lymphoma (DLBCL) receive milademetan alone with different dose schedules. Receives: Drug: Milademetan

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Screening until end of treatment visit, up to approximately 7 years 2 months
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.
Measured: Cycle 1, Day 1 to Day 28 (each cycle, 28 days)
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.
Measured: Screening up to Cycle 3 and beyond, Day 1 (each cycle, 28 days)

Secondary outcomes (6)

Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of Milademetan In Participants Receiving Milademetan
Plasma pharmacokinetic parameters of DS-3032a were calculated using noncompartmental methods.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
Pharmacokinetic Parameter Apparent Clearance (CL/F) of Milademetan In Participants Receiving Milademetan
Plasma pharmacokinetic parameters of DS-3032a were calculated using noncompartmental methods.
Measured: 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)
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.
Measured: 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)
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.
Measured: Cycle 1, Day 15 and Cycle 1, Days 18 to 21 (each cycle is 28 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

11 Jul 20133 Dec 2020

First posted13 Jun 2013 (estimated)
Study start11 Jul 2013
Primary completion8 Oct 2020
Study completion3 Dec 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
More trials run by Daiichi SankyoThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 107 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01877382
Sponsor's protocol ID: DS3032-A-U101
Status last verified: Mar 2025
First submitted: 11 Jun 2013
Last updated: 27 Mar 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Publications

Gounder MM, Bauer TM, Schwartz GK, Weise AM, LoRusso P, Kumar P, Tao B, Hong Y, Patel P, Lu Y, Lesegretain A, Tirunagaru VG, Xu F, Doebele RC, Hong DS. A First-in-Human Phase I Study of Milademetan, an MDM2 Inhibitor, in Patients With Advanced Liposarcoma, Solid Tumors, or Lymphomas. J Clin Oncol. 2023 Mar 20;41(9):1714-1724. doi: 10.1200/JCO.22.01285. Epub 2023 Jan 20.
PubMed 36669146

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 27 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1 Multiple Ascending Dose Study of Milademetan in Subjects With Advanced Solid Tumors or Lymphomas
ClinicalTrials.gov ID: NCT01877382
Acronym / sponsor ID: DS3032-A-U101
Conditions: Advanced Solid Tumor, Lymphoma
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 107 participants (actual)
Lead sponsor: Daiichi SankyoIndustry (pharma, biotech, devices)
Study start: 11 Jul 2013 (actual)
Primary completion: 8 Oct 2020 (actual)
Study completion: 3 Dec 2020 (actual)
First posted: 13 Jun 2013 (estimated)
Results: Posted 18 Jul 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Part 1, Milademetan Alone	Experimental	Drug: MilademetanParticipants receive milademetan alone with different dose schedules.
Part 2, Milademetan Alone	Experimental	Drug: MilademetanParticipants with advanced melanoma and diffuse large B cell lymphoma (DLBCL) receive milademetan alone with different dose schedules.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (26 listed)

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.
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.
Man or woman ≥ 18 years old.

Key exclusion criteria (17 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MilademetanDS-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.	Drug	Part 1, Milademetan Alone
MilademetanMilademetan will be administered as a single oral capsule or as a combination of multiple oral capsules containing 5, 20, 80, and/or 200 mg. An alternate combination of 30 and/or 100 mg capsules of milademetan may be utilized.	Drug	Part 2, Milademetan Alone

Primary outcome

Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan
Time frame: 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
Time frame: 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
Time frame: 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.

6 secondary outcomes

Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of Milademetan In Participants Receiving Milademetan
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)
Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan
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)
Pharmacokinetic Parameter Time to Reach Maximum Plasma Concentration (Tmax) of Milademetan In Participants Receiving Milademetan
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)
Pharmacokinetic Parameter Apparent Clearance (CL/F) of Milademetan In Participants Receiving Milademetan
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)
Pharmacokinetic Parameter Elimination Terminal Half Life Half-Life (T1/2) of Milademetan In Participants Receiving Milademetan
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)
Mean Fold Change From Baseline in Serum MIC-1 Levels in Participants Receiving Milademetan
Time frame: Cycle 1, Day 15 and Cycle 1, Days 18 to 21 (each cycle is 28 days)

Results and safety

Results posted to the registry on 18 Jul 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1: 15 mg/Day Milademetan	3	0
Cohort 2: 30 mg/Day Milademetan	1	0
Cohort 3: 60 mg/Day Milademetan	1	0
Cohort 4: 120 mg/Day Milademetan	13	0
Cohort 5: 240 mg/Day Milademetan	2	0
Cohort 6: 160 mg/Day Milademetan	5	0
Cohort 7b: 90 mg/Day Milademetan	9	0
Cohort 8c: 90 mg/Day Milademetan	15	0
Cohort 9d: 120 mg/Day Milademetan	6	0
Cohort 10e: 120 mg/Day Milademetan	3	0
Cohort 11e: 200 mg/Day Milademetan	3	0
Cohort 12d: 200 mg/Day Milademetan	3	0
Cohort 13e: 260 mg/Day Milademetan	20	0
Cohort 14e: 340 mg/Day Milademetan	3	0
Expansion Cohort: 120 mg/Day Milademetan	0	0

Primary outcome: Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan

Time frame: Screening until end of treatment visit, up to approximately 7 years 2 months. Count of participants. Unit: Participants

Measure	Cohort 1: 15 mg/Day Milademetan n = 3	Cohort 2: 30 mg/Day Milademetan n = 1	Cohort 3: 60 mg/Day Milademetan n = 1	Cohort 4: 120 mg/Day Milademetan + Expansion Cohort n = 33	Cohort 5: 240 mg/Day Milademetan n = 2	Cohort 6: 160 mg/Day Milademetan n = 5	Cohort 7b: 90 mg/Day Milademetan n = 9	Cohort 8c: 90 mg/Day Milademetan n = 15	Cohort 9d: 120 mg/Day Milademetan n = 6	Cohort 10e: 120 mg/Day Milademetan n = 3	Cohort 11e: 200 mg/Day Milademetan n = 3	Cohort 12d: 200 mg/Day Milademetan n = 3	Cohort 13e: 260 mg/Day Milademetan n = 20	Cohort 14e: 340 mg/Day Milademetan n = 3
Any TEAE	3	1	1	33	2	5	9	15	6	3	3	3	20	3
Nausea	1	0	0	22	2	5	7	13	4	1	2	3	16	2
Diarrhea	0	0	0	16	1	3	4	7	0	1	1	1	9	2
Vomiting	1	0	0	10	2	3	2	4	2	1	1	1	11	2
Constipation	1	0	0	7	1	0	4	5	2	1	1	0	5	0
Abdominal pain	1	0	0	5	0	2	1	4	0	1	0	0	3	1
Thrombocytopenia	0	0	0	25	1	4	5	13	2	1	1	2	11	2
Anemia	1	0	1	16	1	3	4	9	2	0	2	2	5	0

Population analysed: Treatment-emergent adverse events (TEAEs) were assessed in the Safety Analysis Set.

Primary outcome: Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE

Time frame: Cycle 1, Day 1 to Day 28 (each cycle, 28 days). Count of participants. Unit: Participants

Measure	Cohort 4: 120 mg/Day Milademetan + Expansion Cohort n = 13	Cohort 5: 240 mg/Day Milademetan n = 1	Cohort 6: 160 mg/Day Milademetan n = 5	Cohort 7b: 90 mg/Day Milademetan n = 8	Cohort 9d: 120 mg/Day Milademetan n = 6	Cohort 14e: 340 mg/Day Milademetan n = 3
Any TEAE classified as DLT	2	1	2	1	1	1
Grade 4 DLT	1	1	1	0	0	0
Grade 3 DLT	0	0	1	1	0	1
Grade 2 DLT	1	0	0	0	1	0

Primary outcome: Number of Participants With Melanoma and Diffuse Large B Cell Lymphoma Who Achieved Objective Response

Time frame: Screening up to Cycle 3 and beyond, Day 1 (each cycle, 28 days). Count of participants. Unit: Participants

Measure	Expansion Cohort: 120 mg/Day Milademetan n = 20
Complete response	0
Partial response	1
Stable disease	8
Progressive disease	5
Inevaluable	6
Objective response rate (CR + PR)	1

Population analysed: Objective response was assessed in the Dose Expansion cohort of the Full Analysis Set.

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were collected from screening until end of study, up to approximately 7 years 4 months.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1: 15 mg/Day Milademetan	0 of 3 (0%)	3 of 3 (100%)	0 of 3
Cohort 2: 30 mg/Day Milademetan	0 of 1 (0%)	1 of 1 (100%)	0 of 1
Cohort 3: 60 mg/Day Milademetan	0 of 1 (0%)	1 of 1 (100%)	0 of 1
Cohort 4: 120 mg/Day Milademetan + Expansion Cohort	11 of 33 (33.3%)	33 of 33 (100%)	3 of 33
Cohort 5: 240 mg/Day Milademetan	1 of 2 (50%)	2 of 2 (100%)	0 of 2
Cohort 6: 160 mg/Day Milademetan	2 of 5 (40%)	5 of 5 (100%)	0 of 5
Cohort 7b: 90 mg/Day Milademetan	3 of 9 (33.3%)	9 of 9 (100%)	0 of 9
Cohort 8c: 90 mg/Day Milademetan	2 of 15 (13.3%)	15 of 15 (100%)	1 of 15
Cohort 9d: 120 mg/Day Milademetan	0 of 6 (0%)	6 of 6 (100%)	0 of 6
Cohort 10e: 120 mg/Day Milademetan	2 of 3 (66.7%)	3 of 3 (100%)	0 of 3
Cohort 11e: 200 mg/Day Milademetan	0 of 3 (0%)	3 of 3 (100%)	0 of 3
Cohort 12d: 200 mg/Day Milademetan	0 of 3 (0%)	3 of 3 (100%)	0 of 3
Cohort 13e: 260 mg/Day Milademetan	4 of 20 (20%)	20 of 20 (100%)	3 of 20
Cohort 14e: 340 mg/Day Milademetan	1 of 3 (33.3%)	3 of 3 (100%)	1 of 3

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 36669146Gounder MM, Bauer TM, Schwartz GK, Weise AM, LoRusso P, Kumar P, Tao B, Hong Y, Patel P, Lu Y, Lesegretain A, Tirunagaru VG, Xu F, Doebele RC, Hong DS. A First-in-Human Phase I Study of Milademetan, an MDM2 Inhibitor, in Patients With Advanced Liposarcoma, Solid Tumors, or Lymphomas. J Clin Oncol. 2023 Mar 20;41(9):1714-1724. doi: 10.1200/JCO.22.01285. Epub 2023 Jan 20.
Related InfoLink provided by the sponsor.
Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Global Clinical Leader study director

Daiichi Sankyo

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Milademetan in people with Advanced Solid Tumor and Lymphoma, run by Daiichi Sankyo at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan (time frame: Screening until end of treatment visit, up to approximately 7 years 2 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01877382, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2025.