Melanoma Clinical Trial
Milademetan in Advanced/Metastatic Solid Tumors
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) ≥ 12 using prespecified biomarker criteria.
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 8 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.
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 testing, defined as ≥ 12 copies by central diagnostic laboratory or ≥ 12 copies or 6-fold increase by local testing modalities
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 setting of Gilbert's disease
Prior treatment with a mouse double minute 2 (MDM2) inhibitor
Well-differentiated/dedifferentiated liposarcoma or intimal sarcoma
Primary malignancies that required systemic antineoplastic treatment within the previous 2 years, except for localized cancers that have apparently been cured
Primary brain tumor (e.g., glioma)
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
QTcF at rest, where the mean QTcF interval is > 480 milliseconds
Myocardial infarction within 6 months
Uncontrolled angina pectoris within 6 months
New York Heart Association Class 3 or 4 congestive heart failure
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There are 10 Locations for this study
Palo Alto California, 94305, United States
Fort Myers Florida, 33901, United States
Saint Petersburg Florida, 33705, United States
Boston Massachusetts, 02214, United States
Boston Massachusetts, 02215, United States
Saint Louis Missouri, 63110, United States
New York New York, 10065, United States
Durham North Carolina, 27710, United States
Nashville Tennessee, 37203, United States
Houston Texas, 77030, United States
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