Milademetan has been evaluated in numerous clinical trials spanning early- to late-phase investigations across oncology indications, including acute myeloid leukemia, myelodysplastic syndrome, dedifferentiated liposarcoma, lymphoma, and advanced solid tumors. Sponsored by pharmaceutical companies such as Daiichi Sankyo and Rain Oncology alongside academic institutions like M.D. Anderson Cancer Center and Institut Curie, the clinical landscape includes completed, terminated, and withdrawn studies, as well as pharmacokinetic protocols evaluating cardiac repolarization and food interactions.
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT05932667 | TERMINATED | Advanced or Metastatic Breast Cancer |
Institut Curie |
2023-10-12 | PHASE2 |
| NCT05012397 | TERMINATED | 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 |
Rain Oncology Inc |
2021-11-01 | PHASE2 |
| NCT04979442 | TERMINATED | Dedifferentiated Liposarcoma |
Rain Oncology Inc |
2021-07-14 | PHASE3 |
| NCT05758818 | TERMINATED | Cardiac Repolarization |
Rain Oncology Inc |
2023-04-17 | PHASE1 |
| NCT06090318 | WITHDRAWN | Advanced Solid Tumor; CDKN2A; NSCLC; Urothelial Carcinoma Bladder; Melanoma; Pancreas Adenocarcinoma; HNSCC; Renal Cell Carcinoma; Mesothelioma; Gastric Cancer |
Rain Oncology Inc |
2023-05-19 | PHASE1; PHASE2 |
| NCT03634228 | TERMINATED | Acute Myeloid Leukemia; Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia |
M.D. Anderson Cancer Center |
2018-12-17 | PHASE1; PHASE2 |
| NCT03552029 | TERMINATED | Acute Myeloid Leukemia |
Daiichi Sankyo |
2018-12-12 | PHASE1 |
| NCT01877382 | COMPLETED | Advanced Solid Tumor; Lymphoma |
Daiichi Sankyo |
2013-07-11 | PHASE1 |
| NCT02319369 | TERMINATED | Acute Myelogenous Leukemia; Myelodysplastic Syndrome |
Daiichi Sankyo |
2014-11-25 | PHASE1 |
| NCT02579824 | TERMINATED | Myeloma |
M.D. Anderson Cancer Center |
2016-08-30 | PHASE1 |
| NCT03671564 | COMPLETED | Acute Myeloid Leukemia |
Daiichi Sankyo Co., Ltd. |
2018-08-23 | PHASE1 |
| NCT03614455 | COMPLETED | Pharmacokinetics |
Daiichi Sankyo |
2018-07-13 | EARLY_PHASE1 |
| NCT03647202 | COMPLETED | Food Effects on Pharmacokinetics |
Daiichi Sankyo |
2018-08-16 | EARLY_PHASE1 |
(data from https://clinicaltrials.gov, updated on 2023-12-21)
Mechanism and Biochemical Profile
Appendix RUO and cGMP Quality Standards
| Quality Dimension | RUO (Research Use Only) | cGMP (Current Good Manufacturing Practice) |
|---|---|---|
| Clinical Applicability | Prohibited in human clinical trials or medical diagnostics. | Mandatory for human clinical trials (Phase I–III) and therapies. |
| Regulatory Status | Non-regulated grade; exempt from drug manufacturing laws. | Legally enforced by health authorities (e.g., FDA, EMA, NMPA). |
| Facility Environment | Unclassified analytical or research laboratories. | Validated Cleanrooms (ISO Class 5–8) with continuous monitoring. |
| Quality Control | Basic purity and activity testing. | Rigorous safety release testing (Sterility, Endotoxin, Mycoplasma). |
| Process Validation | Basic equipment calibration; no process validation required. | Full qualification (IQ/OQ/PQ) and complete batch records. |
| Quality Assurance | Vendor self-declared without required formal QMS. | Mandatory QA/QC unit, Change Control, CAPA, and vendor audits. |
| Regulatory Impact | High risk of IND rejection if used as a critical raw material. | Required for IND/NDA filings, supported by Drug Master Files (DMF). |
Footnotes
Regulatory Note: Governed by FDA (21 CFR Parts 210/211/312), EMA (EudraLex Vol 4), ICH Guidelines (E6/Q7/Q9/Q10), and compendial standards (USP <71>/<85>/<1043>).