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


  • Org Study ID: RAIN-3202
  • Secondary ID: N/A
  • NCT ID: NCT05012397
  • Sponsor: Rain Oncology Inc


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.


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.

  • Overall Status
  • Start Date
    November 1, 2021
  • Phase
    Phase 2
  • Study Type


Primary Outcome 1 - Measure: 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 criteria

Primary Outcome 1 - Timeframe: 3 years


  • 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


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
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

- Uncontrolled hypertension

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No


Name: N/A

Role: N/A

Affiliation: N/A

Overall Contact

Name: N/A

Phone: 5109535559

Email: rain3202@rainoncology.com


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