Advanced Solid and Hematological TP53wt Tumors
Conditions
Keywords
HDM201,TP53wt, p53, MDM2, HDM2, advanced tumors, BLRM (Bayesian logistic regression model)
Brief summary
To determine and evaluate a safe and tolerated dose of HDM201 in adult patients with selected advanced tumors characterized by wild-type TP53.
Interventions
DRUGHDM201
DRUGancillary treatment
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient with a TP53wt locally advanced or metastatic solid malignancy and with measurable or non-measurable (but evaluable) disease as determined by RECIST 1.1 criteria. * Patients with the TP53wt hematological tumors (AML, ALL, HR-MDS) who have failed prior therapies or who are considered inappropriate candidates for standard induction therapy. Other protocol-defined inclusion criteria may apply
Exclusion criteria
* Prior treatment with compounds with the same mode of action * Subjects with significant or uncontrolled cardiovascular disease * History of thromboembolic or cerebrovascular events within the last 6 months, including transient ischemic attack, cerebrovascular accident, deep vein thrombosis, or pulmonary embolism * Previous and concomitant therapy that precludes enrollment, as defined in the protocol * Known Human Immunodeficiency Virus (HIV) infection and/or active Hepatitis B or Hepatitis C infection * Patients who have undergone major surgery within the 2 weeks prior to starting study treatment or who have not fully recovered from previous surgery * Women of child-bearing potential, unless they are using highly effective methods of contraception during dosing and for 2 weeks after study drug discontinuation * Pregnant or nursing women Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose limiting toxicities (DLTs) | up to 28 days | DLTs in the first cycle of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with adverse events (AEs) | For the duration of treatment, an average of 16 weeks | Number of patients with AEs as a measure of Safety and tolerability of HDM201 single agent. |
| Pharmacokinetics (PK) parameters of HDM201 | Up to 42 days | — |
| Changes from baseline of Pharmacodynamics markers | Baseline, up to 28 days | — |
| Tumor response | Every 8 weeks (for solid tumors), every cycle (for hematological tumors) until end of treatment | end of treatment = 1 year |
Countries
France, Germany, Japan, Netherlands, Singapore, Spain, Taiwan, United States
Outcome results
None listed