Study to Determine and Evaluate a Safe and Tolerated Dose of HDM201 in Patients With Selected Advanced Tumors That Are TP53wt

Study Overview
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Brief Summary
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To determine and evaluate a safe and tolerated dose of HDM201 in adult patients with selected advanced tumors characterized by wild-type TP53.

Official Title
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A Phase I, Open Label, Multicenter, Dose-escalation Study of HDM201 in Adult Patients With Advanced Solid and Hematological Tumors Characterized by Wild-type TP53

Conditions
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Advanced Solid and Hematological TP53wt Tumors

Intervention / Treatment
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* Drug: HDM201
* Drug: ancillary treatment


Participation Criteria
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Eligibility Criteria
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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/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br> | Drug: HDM201<br> <br> Drug: ancillary treatment<br> <br> |
| Experimental: Arm B<br> | Drug: HDM201<br> <br> |
| Experimental: Arm C<br> | Drug: HDM201<br> <br> |
| Experimental: Arm D<br> | Drug: HDM201<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose limiting toxicities (DLTs) | DLTs in the first cycle of treatment. | up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse events (AEs) | Number of patients with AEs as a measure of Safety and tolerability of HDM201 single agent. | For the duration of treatment, an average of 16 weeks | 
| Pharmacokinetics (PK) parameters of HDM201 |  | Up to 42 days | 
| Changes from baseline of Pharmacodynamics markers |  | Baseline, up to 28 days | 
| Tumor response | end of treatment = 1 year | Every 8 weeks (for solid tumors), every cycle (for hematological tumors) until end of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HDM201,TP53wt, p53, MDM2, HDM2, advanced tumors, BLRM (Bayesian logistic regression model)