NCT05012397 · REGISTRY CONDITION SEARCH

Milademetan in Advanced/Metastatic Solid Tumors

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE2
Status at capture: TERMINATED
Registry last update: 2024-10-17

Phase 2, multicenter, single-arm, open-label basket study designed to evaluate the safety and efficacy of milademetan in patients with advanced or metastatic solid tumors refractory or intolerant to standard-of-care therapy that exhibit wild-type (WT) TP53 and MDM2 copy number (CN) ≥ 8 using prespecified biomarker criteria.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

To Determine the ORR of Treatment With Milademetan in Patients With Advanced/Metastatic Solid Tumors With MDM2 Gene Amplification.

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outcome · POSTED

Duration of Response (DOR)

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outcome · POSTED

Progression-free Survival (PFS)

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outcome · POSTED

Growth Modulation Index (GMI)

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outcome · POSTED

Disease Control Rate (DCR)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Histologically and/or cytologically confirmed diagnosis of a cancer that is a locally advanced or metastatic solid tumor * Measurable tumor lesion(s) in accordance with RECIST v1.1 * Received all standard therapy appropriate for their tumor type and stage of disease or, in the opinion of the Investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard-of-care therapy * Resolution of any clinically relevant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy * Presence of WT TP53 and MDM2 gene amplification by tumor tissue/blood testing, defined as ≥ 8 copies in tumor tissue by central laboratory or ≥ 8 copies or 4-fold increase in tumor tissue or blood by local testing * Prescreening for TP53 and MDM2 at a Central Laboratory: * MDM2 amplification: CN unknown and where CN cannot be derived for documentation by interpretation of reported results * MDM2 amplification: CN 6 to 7.9 * MDM2 amplification: 3-3.9-fold increase * MDM2 amplification with CN ≥ 8 and with equivocal TP53 mutation upon discussion with Sponsor's Medical Monitor * ECOG performance status of 0 or 1 * Adequate bone marrow function: * Platelet count ≥ 100 × 10\^9/L * Hemoglobin ≥ 9.0 g/dL * Absolute neutrophil count ≥ 1.5 × 10\^9/L * Adequate renal function * Creatinine clearance ≥ 30mL/min, as calculated using the modified Cockcroft-Gault equation * Adequate hepatic function * Alanine aminotransferase and aspartate aminotransferase ≤ 3 × upper limit of normal (ULN) if no liver metastases are present; ≤ 5 × ULN if liver metastases are present * Total bilirubin ≤ 1.5 × ULN, or ≤ 3 x ULN in the presence of liver metastases Exclusion Criteria: * Prior treatment with a murine double minute 2 (MDM2) inhibitor * Well-differentiated/dedifferentiated liposarcoma or intimal sarcoma/cardiac sarcoma * Primary malignancies that required systemic antineoplastic treatment within the previous 2 years, except for localized cancers that have apparently been cured * Has a primary malignant brain tumor of any grade or histology * Untreated brain metastases * Gastrointestinal conditions that could affect the absorption of milademetan, in the opinion of the Investigator * Known HIV infection or active hepatitis B or C infection * Major surgery ≤ 3 weeks of the first dose of milademetan * Curative-intent radiation therapy ≤ 4 weeks or palliative radiation therapy * Uncontrolled or significant cardiovascular disease 1. QTcF at rest, where the mean QTcF interval is \> 480 milliseconds 2. Myocardial infarction within 6 months 3. Uncontrolled angina pectoris within 6 months 4. New York Heart Association Class 3 or 4 congestive heart failure 5. Uncontrolled hypertension
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
260 mg once dailly orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle
intervention Names
Drug: RAIN-32
label
Milademetan (RAIN-32)
type
EXPERIMENTAL

interventions

arm Group Labels
Milademetan (RAIN-32)
description
260 mg once daily orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle
name
RAIN-32
other Names
Milademetan
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 40
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Overall Response Rate (ORR) of treatment with milademetan, as defined as the percentage of patients who have achieved confirmed complete response (CR) or Partial Response (PR) according to RECIST v1.1
measure
To Determine the ORR of Treatment With Milademetan in Patients With Advanced/Metastatic Solid Tumors With MDM2 Gene Amplification.
time Frame
From first dose date to first confirmed complete or partial response or study completion date; up to 23.5 months.

secondary Outcomes

description
DOR defined as the time from the date of first documentation of CR or PR according to RECIST v1.1 to the date of disease progression or death due to any cause according to Investigator assessment
measure
Duration of Response (DOR)
time Frame
From start date of response to first PD or study completion date; up to 23.5 months
description
PFS defined as the time from the date of the first dose of the study drug to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause according to Investigator assessment
measure
Progression-free Survival (PFS)
time Frame
From the first dose date to the earliest date of recurrence, progression, death, or study completion; up to 23.5 months
description
GMI defined as the ratio of Time to Progression (TTP) with the nth line of therapy (TTPn; here defined as milademetan) to the most recent prior line of therapy (TTPn-1)
measure
Growth Modulation Index (GMI)
time Frame
From the start date of the most recent prior line of therapy to the PD date on the study; up to 23.5 months
description
DCR defined as the percentage of patients with confirmed CR, PR, or stable disease (SD) for ≥ 16 weeks
measure
Disease Control Rate (DCR)
time Frame
From first dose date to first CR, PR, or stable disease (SD) >= 16 weeks, or study completion date; up to 23.5 months

Full study description

brief Summary: Phase 2, multicenter, single-arm, open-label basket study designed to evaluate the safety and efficacy of milademetan in patients with advanced or metastatic solid tumors refractory or intolerant to standard-of-care therapy that exhibit wild-type (WT) TP53 and MDM2 copy number (CN) ≥ 8 using prespecified biomarker criteria.
detailed Description: Approximately 65 patients will be enrolled to receive milademetan. Patients will receive the study drug until reaching unequivocal disease progression (per Response Evaluation Criteria in Solid Tumors \[RECIST\] version \[v\]1.1), as determined by the Investigator; experiencing unmanageable toxicity; or until other treatment discontinuation criteria are met. Patients may be treated beyond tumor progression if they are experiencing clinical benefit based on the assessment of the Investigator in discussion with the Medical Monitor. All patients will be followed for documentation of disease progression and survival information (i.e., date and cause of death). Long-term follow-up will continue every 12 weeks (± 7 days) until the endpoint of death, the patient is lost to follow-up, or for 24 months following the final dose of the study drug, whichever comes first.

Source references

references

citation
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.
pmid
36669146
type
BACKGROUND

Source notices and limitations

Discovery and provenance

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Preserved source evidence · Not medical advice