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Solid Tumors and Hematologic MalignancyPhase 1/2NCT02431260

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

A Phase 1/2 study testing INCB054329 Monotherapy in people with Solid Tumors and Hematologic Malignancy, run by Incyte Corporation at 12 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumors and Hematologic Malignancy
What is being tested?
INCB054329 Monotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
69 participants
Where
12 sitesUnited States
Study dates
14 Apr 2015to 31 Jan 2018
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 10Show fewer
  • 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

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

United States12 sites

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • John Hopkins

    Baltimore, Maryland, 21287-0013

  • Northwestern Memorial Hospital

    Chicago, Illinois, 60611

  • The University of Chicago Medical Center

    Chicago, Illinois, 60637

  • Sarah Cannon Research Institute Research Center

    Denver, Colorado, 80218

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Horizon Oncology Center

    Lafayette, Indiana, 47905

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232-0021

  • University of California, San Francisco, Medical Center at Mount Zion

    San Francisco, California, 94115

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98109

  • Washington University School of Medicine in St. Louis

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: 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).

Being tested
INCB054329 Monotherapy
Keywords
solid tumor, lymphoma, BET bromodomain inhibitor, BRD, Diffuse large B-cell lymphoma (DLBCL), Burkitt's lymphoma, c-MYC, colorectal cancer, Non-small cell lung cancer, Pancreatic adenocarcinoma, castration-resistant prostate cancer, breast cancer, NUT midline carcinoma, leukemia, acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), myeloproliferative neoplasms, myelofibrosis (MF), multiple myeloma (MM), MDS/MPN
Medical subject headings
Hematologic Neoplasms, Lymphoma, Lymphoma, Large B-Cell, Diffuse, Burkitt Lymphoma, Colorectal Neoplasms, Carcinoma, Non-Small-Cell Lung, Breast Neoplasms, Leukemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • INCB054329 MonotherapyDrug

    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

Study groups in NCT02431260
Study groupRoleWhat they receive
INCB054329 MonotherapyExperimentalNot described
Receives: Drug: INCB054329 Monotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With a Treatment-emergent Adverse Event (TEAE)

    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.

    Measured: up to 30 days

Secondary outcomes (10)

  1. Maximum Plasma Concentration (Cmax) Analysis of INCB054329

    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.

    Measured: Summary of steady-state PK parameters by dosing regimen at Day 15

  2. Time to Maximum Plasma Concentration (Tmax) Analysis of INCB054329

    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.

    Measured: Summary of steady-state PK parameters by dosing regimen at Day 15

  3. Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) Analysis of INCB054329

    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.

    Measured: Summary of steady-state PK parameters by dosing regimen at Day 15

  4. AUC0-t Analysis of INCB054329

    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.

    Measured: Summary of steady-state PK parameters by dosing regimen at Day 15

  5. Cl/F Analysis of INCB054329

    Cl/F is the apparent oral dose clearance measured at steady state (Day 15). Study drug was administered with 240 mL of water.

    Measured: Summary of steady-state PK parameters by dosing regimen at Day 15

  6. Pharmacodynamics (PD) Analysis - Total c-Myc % Inhibition Versus INCB054329

    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.

    Measured: Day 15 in all cohorts

  7. Objective Response Rate (ORR)

    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).

    Measured: Baseline through end of study, up to 6 months

  8. Duration of Response (DOR)

    Defined as the time from earliest date of disease response until earliest date of disease progression or death.

    Measured: Baseline through end of study, up to 6 months

  9. Progression Free Survival (PFS)

    PFS is the time from start of study treatment to first documentation of progression, or to death due to any cause, whichever comes first

    Measured: Baseline through end of study, up to 6 months

  10. Overall Survival (OS)

    OS is defined as the time from the date of randomization to the date of the participant's death.

    Measured: Baseline through end of study, up to 6 months for participants in Part 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Apr 2015 (estimated)
  2. Study start14 Apr 2015
  3. Primary completion31 Jan 2018
  4. Study completion31 Jan 2018

Why it stopped: As of 31 JAN 2018, the study was terminated by the sponsor due to PK variability.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Intervention model
Sequential
Masking
None (open label)
Enrolment
69 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02431260
Sponsor's protocol ID
INCB 54329-101
Status last verified
May 2019
First submitted
27 Apr 2015
Last updated
14 Jun 2019
Data monitoring committee
No
Individual data sharing
No
Expanded access
Available

Publications

  • Falchook G, Rosen S, LoRusso P, Watts J, Gupta S, Coombs CC, Talpaz M, Kurzrock R, Mita M, Cassaday R, Harb W, Peguero J, Smith DC, Piha-Paul SA, Szmulewitz R, Noel MS, Yeleswaram S, Liu P, Switzky J, Zhou G, Zheng F, Mehta A. Development of 2 Bromodomain and Extraterminal Inhibitors With Distinct Pharmacokinetic and Pharmacodynamic Profiles for the Treatment of Advanced Malignancies. Clin Cancer Res. 2020 Mar 15;26(6):1247-1257. doi: 10.1158/1078-0432.CCR-18-4071. Epub 2019 Sep 16.

    PubMed 31527168

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing INCB054329 Monotherapy in people with Solid Tumors and Hematologic Malignancy, run by Incyte Corporation at 12 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 14 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With a Treatment-emergent Adverse Event (TEAE) (time frame: up to 30 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02431260, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2019.

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