Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Siremadlin
HDM201 · 4 trials · 4 indications
Maximum Observed Blood Concentrations (Cmax) for siremadlin. Blood samples will be collected to measure Cmax at indicated timepoints. Pharmacokinetic (PK) parameters will be calculated based on siremadlin blood concentrations.
Area Under Plasma Concentration-time Curve from time zero to the last measurable concentration sampling time (AUClast) for siremadlin. Blood samples will be collected to measure AUClast at indicated timepoints. Pharmacokinetic (PK) parameters will be calculated based on siremadlin blood concentrations.
Area Under Plasma Concentration from time zero to time "t" (AUC0-t). The definition of "t" may be data driven post-hoc to mitigate bias in the exposure comparision due to between-group differences in Tlast for siremadlin. Blood samples will be collected to measure AUC0-t at indicated timepoints. Pharmacokinetic (PK) parameters will be calculated based on siremadlin blood concentrations.
Area Under Plasma Concentration from time zero to 24-hour post-dose sampling time (AUC0-24h) for siremadlin. Blood samples will be collected to measure AUC0-24h at indicated timepoints. Pharmacokinetic (PK) parameters will be calculated based on siremadlin blood concentrations.
Last measurable plasma concentration (Tlast) for siremadlin. Blood samples will be collected to measure Tlast at indicated timepoints. Pharmacokinetic (PK) parameters will be calculated based on siremadlin blood concentrations.
Time to Reach Maximum Blood Concentrations (Tmax) for siremadlin. Blood samples will be collected to measure Tmax at indicated timepoints. Pharmacokinetic (PK) parameters will be calculated based on siremadlin blood concentrations.
Apparent total body clearance of siremadlin from plasma (CL/F). Blood samples will be collected to measure CL/F at indicated timepoints. Pharmacokinetic (PK) parameters will be calculated based on siremadlin blood concentrations.
Apparent volume of distribution during terminal elimination phase (Vz/F) of siremadlin. Blood samples will be collected to estimate Vz/F at indicated timepoints. Pharmacokinetic (PK) parameters will be calculated based on siremadlin blood concentrations.
Terminal Elimination Half-life (T1/2) for siremadlin. Blood samples will be collected to measure T1/2 at indicated timepoints. Pharmacokinetic (PK) parameters will be calculated based on siremadlin blood concentrations.
Area Under Plasma Concentration from time zero to infinity (AUCinf). Blood samples will be collected to measure AUCinf at indicated timepoints. Pharmacokinetic (PK) parameters will be calculated based on siremadlin blood concentrations.
A dose-limiting toxicity (DLT) is defined as an adverse event (AE) or abnormal laboratory value considered by the Investigator to be at least possibly related to siremadlin as a single contributor or in combination with other component(s) of study treatment that occurs beginning the first day of siremadlin dosing in the study until end of cycle 1.
Assessed by CR rate. CR rate is defined as the percentage of participants with best overall response of complete remission (CR) as per investigator assessment.
DLTs in the first cycle of treatment.
as measured by AUC0-24h
To assess the preliminary anti-tumor activity of HDM201 in combination with LEE011 in liposarcoma
DLTs in the first cycle of treatment.
| Arm | Type | Description |
|---|---|---|
| Group 1: Healthy Control | EXPERIMENTAL | Each healthy participant will receive a single dose of HDM201 |
| Group 2: Mild; Child-Pugh A | EXPERIMENTAL | Each participant with mild Child-Pugh will receive a single dose of HDM201 |
| Group 3: Moderate; Child-Pugh B | EXPERIMENTAL | Each participant with moderate Child-Pugh will receive a single dose of HDM201 |
| Group 4: Severe; Child-Pugh C | EXPERIMENTAL | Each participant with severe Child-Pugh will receive a single dose of HDM201 |
| Arm 1: Adult participants with unfit AML who responded sub-optimally to standard of care | EXPERIMENTAL | Unfit adult participants with unfit AML who responded sub-optimally to at least 2 and not more than 4 cycles of first-line venetoclax plus azacitidine therapy. Siremadlin was adminstered at a dose of 20 mg QD which could be increased based on toxicities; venetoclax was administered at 400 mg once daily and azacitidine was administered at 75 mg/m\^2. |
| Arm 2: Adult participants with newly diagnosed unfit AML with high risk clinical features | EXPERIMENTAL | Adult participants with unfit AML who were newly diagnosed and presenting with high-risk clinical features (which related to factors conferring to a low likelihood of response to venetoclax plus azacitidine) and with adverse genetic risk stratification (according to ELN 2022) (Except TP53 mutation positive participants). Siremadlin was administered at a dose of 20 mg QD which could be increased based on toxicities; venetoclax was administered at 400 mg once daily and azacitidine was administered at 75 mg/m\^2. |
| HDM201+LEE011 | EXPERIMENTAL | - |
| Arm A | EXPERIMENTAL | - |
| Arm B | EXPERIMENTAL | - |
| Arm C | EXPERIMENTAL | - |
| Arm D | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Siremadlin | DRUG | HDM201 capsule |
| venetoclax | DRUG | Venetoclax is a tablet taken orally once a day (QD) and comes in 10 mg, 50 mg and 100 mg strengths. |
| azacitidine | DRUG | Azacitidine is a powder for suspension for injection or powder for solution for infusion taken intravenously or subcutaneously comes in 100 mg but was administered according to standard local clinical practice. |
| HDM201 | DRUG | - |
| LEE011 | DRUG | - |
| ancillary treatment | DRUG | - |
Key Inclusion Criteria: All participants: * Male and non-child-bearing potential females between 18 and 75 years of age, inclusive, at Screening. * Participant must have been a non-smoker or moderate smoker (up to 10 cigarettes or equivalent nicotine containing products per day) at Screening. Part...
HDM201 is an investigational small molecule being studied for the treatment of advanced solid and hematological TP53 wild-type tumors and liposarcoma. It is currently in Phase 1 clinical development and is not yet approved by regulatory authorities.
HDM201 targets MDM2, a protein that regulates the tumor suppressor p53. By inhibiting MDM2, HDM201 is designed to stabilize and activate p53 in TP53 wild-type tumors, potentially leading to cancer cell death.
HDM201 is being developed by Novartis AG, a multinational pharmaceutical company listed on the New York Stock Exchange under the ticker symbol NVS.
HDM201 is in Phase 1 clinical development. Two Phase 1 trials have been completed, one in liposarcoma and one in advanced TP53 wild-type tumors. The drug remains investigational and has not received FDA approval.
HDM201 has been studied in two completed Phase 1 trials. NCT02343172 evaluated HDM201 in combination with LEE011 in patients with liposarcoma, enrolling 74 participants. NCT02143635 assessed HDM201 as a single agent in advanced TP53 wild-type tumors, enrolling 208 participants across multiple countries.