Phase I Study of MIK665, a Mcl-1 Inhibitor, in Patients With Refractory or Relapsed Lymphoma or Multiple Myeloma

Study Overview
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Brief Summary
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The purpose of this first in human study is to assess safety, tolerability, PK and preliminary clinical activity and to estimate the MTD(s)/RDE(s) of MIK665 (also referred as S64315) as single agent administered intravenously (i.v.) in adult patients with refractory or relapsed lymphoma or multiple myeloma.

Detailed Description
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The design of this phase I, open label, dose finding study was chosen in order to characterize the safety and tolerability of MIK665 and to determine the Maximal Tolerated Dose(s) (MTD(s)) and/or Recommended Dose(s) for Expansion (RDE(s)). This study will utilize a Bayesian Hierarchical model to guide dose escalation and estimate the MTD(s) based on the dose-DLT relationship(s) for MIK665 in the indications. The expansion part of the study will employ an open-label multiple arm design. The purpose of the expansion part is to further assess safety, tolerability, PK, PD and the anti-tumor activity of MIK665 at the selected RDE/s for Multiple Myeloma (MM) and MYC positive Diffuse large B-Cell Lymphoma (DLBCL) identified in the dose-escalation part.

Official Title
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Phase I Open Label, Multi-center Study to Characterize the Safety, Tolerability and Pharmacokinetics of Intravenously Administered MIK665, a Mcl-1 Inhibitor, in Patients With Refractory or Relapsed Lymphoma or Multiple Myeloma

Conditions
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Multiple Myeloma (MM), Lymphoma, Large B-Cell, Diffuse (DLBCL), Lymphoma

Intervention / Treatment
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* Drug: MIK665


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Age ≥ 18 years. Histologically confirmed lymphoma (WHO classification), or confirmed MM (IMWG), that is relapsed and/or refractory. Other Inclusion Criteria May Apply. Exclusion Criteria Known history of chronic liver disease History of chronic pancreatitis. Prior treatment with Mcl-1 inhibitor. Other 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MIK665<br> | Drug: MIK665<br>* MIK665<br>* Other names: S64315;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of AEs and SAEs, incl. changes in laboratory parameters, vital signs and ECGs. |  | 2 years | 
| Incidence of DLTs during the first cycle of treatment with single agent MIK665 during the dose escalation phase only |  | 2 years | 
| Tolerability: Dose interruptions |  | 2 years | 
| Tolerability: Dose reductions |  | 2 years | 
| Tolerability: Dose intensity |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall response (BOR) per International Myeloma Working Group (IMWG) criteria for Myeloma; and per revised criteria for staging of the International Working Group (IWG) guidelines for Lymphoma |  | 2 years | 
| Area Under Curve (AUC) | Plasma PK parameter | 2 years | 
| Maximum Plasma Concentration (Cmax) | Plasma PK parameter | 2 years | 
| Terminal elimination half-life (T1/2) | Plasma PK parameter | 2 years | 
| Apparent volume of distribution (Vz) | Plasma PK parameter | 2 years | 
| Clearance (CL) | Plasma PK parameter | 2 years | 
| Duration of Response (DOR)per International Myeloma Working Group (IMWG) criteria for Myeloma; and per revised criteria for staging of the International Working Group (IWG) guidelines for Lymphoma |  | 2 years | 
| Progression Free Survival (PFS) per International Myeloma Working Group (IMWG) criteria for Myeloma; and per revised criteria for staging of the International Working Group (IWG) guidelines for Lymphoma |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dlbcl, multiple myeloma, lymphoma