An Open-Label, Dose-Escalation Study of INCB054329 in Patients With Advanced Malignancies

May 17, 2019 updated by: Incyte Corporation

A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of INCB054329 in Subjects With Advanced Malignancies

This was a study of INCB054329 given to patients with advanced malignancies that were conducted in three treatment groups. Each treatment group had a dose escalation (Part 1) and a dose expansion (Part 3), two of the treatment groups also had an intra-patient dose titration (Part 2).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

69

Phase

  • Phase 2
  • Phase 1

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90048
        • Cedars-Sinai Medical Center
      • San Francisco, California, United States, 94115
        • University of California, San Francisco, Medical Center at Mount Zion
    • Colorado
      • Denver, Colorado, United States, 80218
        • Sarah Cannon Research Institute Research Center
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern Memorial Hospital
      • Chicago, Illinois, United States, 60637
        • The University of Chicago Medical Center
    • Indiana
      • Lafayette, Indiana, United States, 47905
        • Horizon Oncology Center
    • Maryland
      • Baltimore, Maryland, United States, 21287-0013
        • John Hopkins
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Comprehensive Cancer Center
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine in St. Louis
    • Tennessee
      • Nashville, Tennessee, United States, 37232-0021
        • Vanderbilt University Medical Center
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas MD Anderson Cancer Center
    • Washington
      • Seattle, Washington, United States, 98109
        • Seattle Cancer Care Alliance

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Key Inclusion Criteria:

  • Confirmed diagnosis of advanced malignancy:

    • Treatment Group A (TGA): Part 1 and Part 2: Any advanced solid tumor or lymphoma; Part 3: Histologically confirmed disease in specific solid tumors and lymphomas
    • Treatment Group B (TGB): Acute Leukemia (Part 3 - acute myeloid leukemia [AML] only), myelodysplastic syndrome (MDS), myelodysplastic /myeloproliferative neoplasms (MDS/MPN) and myelofibrosis (MF)
    • Treatment Group C (TGC): Multiple myeloma
  • Progressed following at least 1 line of prior therapy and there is no further approved therapy available that has been demonstrated to prolong survival (including subjects who are intolerant to the approved therapy)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 in Parts 1 and 2 dose escalation and titration, and 0, 1, 2 in Part 3 dose expansion

Key Exclusion Criteria:

  • Inadequate hematopoietic, liver, endocrine or renal function

  • Receipt of anticancer medications or investigational drugs within the following interval before the first administration of study drug:

    • < 6 weeks for mitomycin-C or nitrosoureas
    • < 5 half-lives or 14 days, whichever is longer, for any investigational agent (for any indication)
    • < 28 days for any antibodies or biological therapies
    • < 5 half-lives for all other anticancer medications, or sponsor approval
  • Prior radiotherapy within 2 weeks prior to first dose of study drug
  • Untreated brain or central nervous system (CNS) metastases
  • Type 1 diabetes or uncontrolled Type 2 diabetes
  • Any sign of clinically significant bleeding

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Interventional Model: SEQUENTIAL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: INCB054329 Monotherapy
Drug: INCB054329 Monotherapy
Initial cohort dose of INCB054329 monotherapy at the protocol-specified starting dose in the treatment group A (TGA), with subsequent cohort escalations in the three treatment groups (TGA, TGB, and TGC) based on protocol-specific criteria

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With a Treatment-emergent Adverse Event (TEAE)
Time Frame: up to 30 days
TEAE is defined as an adverse event reported for the first time or worsening of a pre-existing event after the first dose of study treatment.
up to 30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Plasma Concentration (Cmax) Analysis of INCB054329
Time Frame: Summary of steady-state PK parameters by dosing regimen at Day 15

Cmax is defined as the maximum observed serum concentration measured at steady state (Day 15).

Study drug was administered with 240 mL of water. Summary of Steady-State, Day 15, was evaluated by dosing regimen.
Summary of steady-state PK parameters by dosing regimen at Day 15
Time to Maximum Plasma Concentration (Tmax) Analysis of INCB054329
Time Frame: Summary of steady-state PK parameters by dosing regimen at Day 15
Tmax is the time to maximum (peak) drug serum concentration. Study drug was administered with 240 mL of water. Summary of Steady-State, Day 15, was evaluated by dosing regimen.
Summary of steady-state PK parameters by dosing regimen at Day 15
Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) Analysis of INCB054329
Time Frame: Summary of steady-state PK parameters by dosing regimen at Day 15
Minimum observed plasma concentration measured at steady state (Day 15). Study drug was administered with 240 mL of water. Summary of Steady-State, Day 15, was evaluated by dosing regimen.
Summary of steady-state PK parameters by dosing regimen at Day 15
AUC0-t Analysis of INCB054329
Time Frame: Summary of steady-state PK parameters by dosing regimen at Day 15

AUC0-t is the area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t measured at steady state (Day 15).

Study drug was administered with 240 mL of water.
Summary of steady-state PK parameters by dosing regimen at Day 15
Cl/F Analysis of INCB054329
Time Frame: Summary of steady-state PK parameters by dosing regimen at Day 15
Cl/F is the apparent oral dose clearance measured at steady state (Day 15). Study drug was administered with 240 mL of water.
Summary of steady-state PK parameters by dosing regimen at Day 15
Pharmacodynamics (PD) Analysis - Total c-Myc % Inhibition Versus INCB054329
Time Frame: Day 15 in all cohorts

The half maximal inhibitory concentration (IC50) of INCB054329 was measured. The maximal inhibition of total c-Myc was correlated to the level of drug exposure and demonstrated a high degree of interparticipant variability, parallel to the PK data.

The measure was performed as a value across all cohorts. The entire dose escalation data set was used to create the relationship curve. Analysis of individual cohorts contained too few subjects and was biased toward one region of the curve so that the relationship was poorly defined.

Individual data points from all subjects were subjected to a nonlinear least squares regression analysis with no weighting, resulting in a sigmoidal dose response curve defining the relationship. The numerical value given is the projected INCB0054329 concentration in nM that produced 50% inhibition of c-myc expression.
Day 15 in all cohorts
Objective Response Rate (ORR)
Time Frame: Baseline through end of study, up to 6 months
Defined as the percentage of subjects having complete response (CR) or partial response (PR). The best overall response was defined as the best response recorded before and including the first event of Progressive disease (PD).
Baseline through end of study, up to 6 months
Duration of Response (DOR)
Time Frame: Baseline through end of study, up to 6 months
Defined as the time from earliest date of disease response until earliest date of disease progression or death.
Baseline through end of study, up to 6 months
Progression Free Survival (PFS)
Time Frame: Baseline through end of study, up to 6 months
PFS is the time from start of study treatment to first documentation of progression, or to death due to any cause, whichever comes first
Baseline through end of study, up to 6 months
Overall Survival (OS)
Time Frame: Baseline through end of study, up to 6 months for participants in Part 2
OS is defined as the time from the date of randomization to the date of the participant's death.
Baseline through end of study, up to 6 months for participants in Part 2

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Incyte Corporation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

April 14, 2015

Primary Completion (ACTUAL)

January 31, 2018

Study Completion (ACTUAL)

January 31, 2018

Study Registration Dates

First Submitted

April 27, 2015

First Submitted That Met QC Criteria

April 29, 2015

First Posted (ESTIMATE)

April 30, 2015

Study Record Updates

Last Update Posted (ACTUAL)

June 14, 2019

Last Update Submitted That Met QC Criteria

May 17, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • INCB 54329-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Solid Tumors and Hematologic Malignancy

Clinical Trials on INCB054329 Monotherapy

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Gambia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe