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

Solid Tumors and Hematologic Malignancy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02431260
• Other study ID #: INCB 54329-101
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: April 14, 2015
• Est. completion date: January 31, 2018

Study information

• Verified date: May 2019
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 69
• Est. completion date: January 31, 2018
• Est. primary completion date: January 31, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumors and Hematologic Malignancy

Intervention

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

Locations

Country	Name	City	State
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	John Hopkins	Baltimore	Maryland
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	The University of Chicago Medical Center	Chicago	Illinois
United States	Sarah Cannon Research Institute Research Center	Denver	Colorado
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Horizon Oncology Center	Lafayette	Indiana
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Washington University School of Medicine in St. Louis	Saint Louis	Missouri
United States	University of California, San Francisco, Medical Center at Mount Zion	San Francisco	California
United States	Seattle Cancer Care Alliance	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	up to 30 days
Secondary	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.	Summary of steady-state PK parameters by dosing regimen at Day 15
Secondary	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.	Summary of steady-state PK parameters by dosing regimen at Day 15
Secondary	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.	Summary of steady-state PK parameters by dosing regimen at Day 15
Secondary	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.	Summary of steady-state PK parameters by dosing regimen at Day 15
Secondary	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.	Summary of steady-state PK parameters by dosing regimen at Day 15
Secondary	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.	Day 15 in all cohorts
Secondary	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).	Baseline through end of study, up to 6 months
Secondary	Duration of Response (DOR)	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
Secondary	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	Baseline through end of study, up to 6 months
Secondary	Overall Survival (OS)	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