Milademetan in Advanced/Metastatic Solid Tumors

NCT ID: NCT05012397

Last Updated: 2024-10-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-01
• Study Completion Date: 2023-10-15

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.

Conditions

Solid Tumors; Head and Neck Carcinoma; Cholangiocarcinoma; Sarcoma; Lung Adenocarcinoma; Bladder Urothelial Carcinoma; Stomach Adenocarcinoma; Breast Cancer Invasive; Ovarian Carcinoma; Cervical Cancer; Non Small Cell Lung Cancer; Gastric Cancer; Biliary Tract Cancer; Melanoma; Pancreas Cancer; MDM2 Gene Amplification; Testicular Germ Cell Tumor; Adrenocortical Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Milademetan (RAIN-32)

260 mg once dailly orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle

Group Type: EXPERIMENTAL

RAIN-32

Intervention Type: DRUG

260 mg once daily orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle

Interventions

RAIN-32

260 mg once daily orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle

Intervention Type: DRUG

Other Intervention Names

Milademetan

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rain Oncology Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Stanford University Medical Center

Palo Alto, California, United States

Florida Cancer Specialists

Fort Myers, Florida, United States

Florida Cancer Specialists

St. Petersburg, Florida, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Washington University School of Medicine

St Louis, Missouri, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Hematology Oncology Associates of Central NY

Syracuse, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Sanford Health

Sioux Falls, South Dakota, United States

Tennessee Oncology, PLLC

Nashville, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

Northwest Medical Specialities

Tacoma, Washington, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 36669146 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

RAIN-3202

Identifier Type: -

Identifier Source: org_study_id