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A Phase 2 Basket Study of Milademetan in Advanced/Metastatic Solid Tumors

INTRODUCTION

  • Org Study ID: RAIN-3202
  • Secondary ID: N/A
  • NTC ID: NCT05012397
  • Sponsor: Rain Therapeutics Inc.

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) ≥ 12 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 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.

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

PRIMARY OUTCOMES

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

CONDITION

  • 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

ELIGIBILITY

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 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
Exclusion Criteria:
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

- Uncontrolled hypertension

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: N/A

Role: N/A

Affiliation: N/A

Overall Contact

Name: N/A

Phone: 5109535559

Email: rain3202@rainthera.com

LOCATION

Facility Status Contact