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

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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma (MM), Lymphoma, Large B-Cell, Diffuse (DLBCL), Lymphoma
• Intervention / Treatment: Drug: MIK665

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Novartis Investigative Site
• France
  • Nantes Cedex 1, France, 44093
    • Novartis Investigative Site
• Germany
  • Heidelberg, Germany, 69120
    • Novartis Investigative Site
  • Kiel, Germany, 24105
    • Novartis Investigative Site
• Italy
  • MI
    • Rozzano, MI, Italy, 20089
      • Novartis Investigative Site
• Japan
  • Fukuoka
    • Fukuoka-city, Fukuoka, Japan, 811-1395
      • Novartis Investigative Site
• Spain
  • Castilla Y Leon
    • Salamanca, Castilla Y Leon, Spain, 37007
      • Novartis Investigative Site
• United States
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center/University of Texas MD Anderson CC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: MIK665	Drug: MIK665; MIK665; Other Names: S64315

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Study Results

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 12, 2017
• Primary Completion (ACTUAL): June 7, 2019
• Study Completion (ACTUAL): June 7, 2019

Study Registration Dates

• First Submitted: December 12, 2016
• First Submitted That Met QC Criteria: December 12, 2016
• First Posted (ESTIMATE): December 14, 2016

Study Record Updates

• Last Update Posted (ACTUAL): August 3, 2021
• Last Update Submitted That Met QC Criteria: July 27, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: lymphoma; multiple myeloma; dlbcl
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Lymphoma, B-Cell; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: CMIK665X2101; 2016-003624-22 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No