Milademetan in Advanced/Metastatic Solid Tumors

October 14, 2024 updated by: Rain Oncology Inc

A Phase 2 Basket Study of Milademetan in Advanced/Metastatic Solid Tumors (MANTRA-2)

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Palo Alto, California, United States, 94305
        • Stanford University Medical Center
    • Florida
      • Fort Myers, Florida, United States, 33901
        • Florida Cancer Specialists
      • Saint Petersburg, Florida, United States, 33705
        • Florida Cancer Specialists
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02214
        • Massachusetts General Hospital
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan-Kettering Cancer Center
      • Syracuse, New York, United States, 13057
        • Hematology Oncology Associates of Central NY
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • Ohio
      • Cincinnati, Ohio, United States, 45267
        • University of Cincinnati Medical Center
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57104
        • Sanford Health
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology, PLLC
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center
    • Washington
      • Tacoma, Washington, United States, 77030
        • Northwest Medical Specialities

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Milademetan (RAIN-32)
260 mg once dailly orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle
Drug: RAIN-32
260 mg once daily orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle
Other Names:
  • Milademetan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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
From first dose date to first confirmed complete or partial response or study completion date; up to 23.5 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Response (DOR)
Time Frame: From start date of response to first PD or study completion date; up to 23.5 months
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
From start date of response to first PD or study completion date; up to 23.5 months
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
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
From the first dose date to the earliest date of recurrence, progression, death, or study completion; up to 23.5 months
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
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)
From the start date of the most recent prior line of therapy to the PD date on the study; up to 23.5 months
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
DCR defined as the percentage of patients with confirmed CR, PR, or stable disease (SD) for ≥ 16 weeks
From first dose date to first CR, PR, or stable disease (SD) >= 16 weeks, or study completion date; up to 23.5 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rain Oncology Inc

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2021

Primary Completion (Actual)

October 15, 2023

Study Completion (Actual)

October 15, 2023

Study Registration Dates

First Submitted

August 13, 2021

First Submitted That Met QC Criteria

August 13, 2021

First Posted (Actual)

August 19, 2021

Study Record Updates

Last Update Posted (Actual)

October 17, 2024

Last Update Submitted That Met QC Criteria

October 14, 2024

Last Verified

October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RAIN-3202

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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