Open-Label Safety and Tolerability Study of INCB057643 in Subjects With Advanced Malignancies

Solid Tumors Clinical Trial

Official title:

A Phase 1/2, Open-Label, Dose-Escalation/Dose-Expansion, Safety and Tolerability Study of INCB057643 in Subjects With Advanced Malignancies

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02711137
• Other study ID #: INCB 57643-101
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: May 18, 2016
• Est. completion date: February 13, 2019

Study information

• Verified date: April 2022
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the Study is to select a dose and assess the safety and tolerability of INCB057643 as a monotherapy (Part 1 and Part 2) and in combination with standard-of-care (SOC) agents (Part 3 and Part 4) for subjects with advanced malignancies.

Part 1 will determine the maximum tolerated dose of INCB057643 and/or a tolerated dose that demonstrates sufficient pharmacologic activity. Part 2 will further evaluate the safety, preliminary efficacy, PK, and PD of the dose(s) selected in Part 1 in select tumor types including solid tumors, lymphomas and other hematologic malignancies. Part 3 will determine the tolerated dose of INCB057643 in combination with select SOC agents; and assess the safety and tolerability of the combination therapy in select advanced solid tumors and hematologic malignancies. Part 4 will further evaluate the safety, preliminary efficacy, PK, and PD of the selected dose combination from Part 3 in 4 specific advanced solid tumor and hematologic malignancies.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 137
• Est. completion date: February 13, 2019
• Est. primary completion date: February 13, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of relapsed or refractory advanced or metastatic malignancies:

• Part 1: solid tumors or lymphomas, or hematologic malignancies

• Part 2: histologically confirmed disease in specific tumor types

• Part 3: advanced solid tumor or hematologic malignancy

• Part 4: select advanced solid tumor or hematologic malignancy

• For Part 1 and 2, subjects must have progressed following at least 1 line of prior therapy and there is no further established therapy that is known to provide clinical benefit (including subjects who are intolerant to the established therapy)

• For Parts 3 and 4, subjects must have progressed following at least 1 line of prior therapy, and the treatment with the select SOC agent is relevant for the specific disease cohort.

• Life expectancy > 12 weeks, for MF subjects in Parts 3 and 4, life expectancy > 24 weeks

• Eastern Cooperative Oncology Group (ECOG) performance status

• Parts 1 and 3: 0 or 1

• Parts 2 and 4: 0, 1, or 2

• Willingness to avoid pregnancy or fathering children

Exclusion Criteria:

• Inadequate bone marrow function per protocol-specified hemoglobin, platelet count, and absolute neutrophil count

• Inadequate organ function per protocol-specified total bilirubin, AST and ALT, creatinine clearance and alkaline phosphatase.

• Receipt of anticancer medications or investigational drugs within protocol-specified intervals

• Unless approved by the medical monitor, may not have received an allogeneic hematopoietic stem cell transplant within 6 months before treatment, or have active graft-versus-host-disease following allogeneic transplant

• Unless approved by the medical monitor, may not have received autologous hematopoietic stem cell transplant within 3 months before treatment

• Any unresolved toxicity = Grade 2 (except stable Grade 2 peripheral neuropathy or alopecia) from previous anticancer therapy

• Radiotherapy within the 2 weeks before initiation of treatment. Palliative radiation treatment to nonindex or bone lesions performed less than 2 weeks before treatment initiation may be considered with medical monitor approval

• Currently active and uncontrolled infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment

• Untreated brain or central nervous system (CNS) metastases or brain/CNS metastases that have progressed

• History or presence of abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful

• Type 1 diabetes or uncontrolled Type 2 diabetes

• HbA1c of = 8% (all subjects will have HbA1c test at screening)

• Any sign of clinically significant bleeding

• Coagulation panel within protocol-specified parameters

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumors

Intervention

Drug:
• INCB057643
Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).
• Gemcitabine
Standard of Care (SOC) agents
• Paclitaxel
Standard of Care (SOC) agents
• Rucaparib
Standard of Care (SOC) agents
• Abiraterone
Standard of Care (SOC) agents
• Ruxolitinib
Standard of Care (SOC) agents
• Azacitidine
Standard of Care (SOC) agents

Locations

Country	Name	City	State
Belgium	Institut Jules Bordet, Clinical Trial Conduct Unit	Brussels
France	HÔPITAL SAINT-LOUIS, Service Hématologie Adultes	Paris
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Alabama	Birmingham	Alabama
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Sarah Cannon Research Institute at Health One	Denver	Colorado
United States	Oncology Consultants, P.A.	Houston	Texas
United States	The Methodist Hospital	Houston	Texas
United States	University of California	La Jolla	California
United States	Sylvester Comprehensive Cancer Center	Miami	Florida
United States	University of Minnesota	Minneapolis	Minnesota
United States	Yale University	New Haven	Connecticut
United States	Hematology - Oncology Associates of Treasure Coast	Port Saint Lucie	Florida
United States	University of Rochester, Wilmot Cancer Center	Rochester	New York
United States	Washington University	Saint Louis	Missouri
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	MultiCare Institute for Research and Innovation	Tacoma	Washington
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  Belgium,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment Emergent Adverse Events (TEAE's).	Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.	From screening through at least 30 days after end of treatment, up to approximately 24 months
Secondary	Percent Inhibition of Total Cellular Myc Protein Concentrations Before and After Administration of INCB057643 When Administered as Monotherapy in an Ex-vivo Assay	An ex vivo assay (utilized in monotherapy only), Measuring Total c-Myc protein expressed from an exogenously added cell line (KMS12BM) to patient plasma, before and after administration of INCB057643.	PD in plasma at pre-dose and 0.5, 1, 2, 4, 6 and 8 hours postdose, for C1D1 and C1D8, and 24hrs post dose for C1D1
Secondary	Objective Response Rate (ORR) With INCB057643 in Solid Tumors	Objective response rate is defined as the proportion of subjects who have an objective response using the applicable disease assessment criteria. ORR was proportion of participants with best overall response [complete response (CR) or partial response (PR)].	Efficacy measures from screening through end of treatment and follow-up (every 9 weeks), up to approximately 24 months
Secondary	Cmax: Maximum Observed Plasma Concentration of INCB057643.	Maximum Observed Plasma Concentration INCB057643 administered as monotherapy in fasted state.	Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D1 and C1D8
Secondary	Tmax: Time to Maximum Plasma Concentration of INCB057643	Time to maximum plasma concentration of INCB057643 administered as monotherapy in fasted state	Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D1 and C1D8
Secondary	AUC0-t: Area Under the Single-dose Plasma Concentration-time Curve of INCB057643	Area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration of INCB057643 administered as monotherapy in fasted state	Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D1
Secondary	AUC0-24: Area Under the Steady-state Plasma Concentration-time Curve of INCB057643 Administered as Monotherapy	Area under the steady-state plasma concentration-time curve over 1 dosing interval from Hour 0 to 24 for QD administration of INCB057643 administered as monotherapy in fasted state	Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D8
Secondary	Part 2 - Cmax: Maximum Observed Plasma Concentration of INCB057643.	Maximum Observed Plasma Concentration INCB057643 administered as monotherapy in fed state.	C2D1
Secondary	Part 2-Tmax: Time to Maximum Plasma Concentration of INCB057643	Time to maximum plasma concentration of INCB057643 administered as monotherapy in fed state	C2D1
Secondary	AUC0-24: Area Under the Steady-state Plasma Concentration-time Curve of INCB057643 Administered as Monotherapy	Area under the steady-state plasma concentration-time curve over 1 dosing interval from Hour 0 to 24 for QD administration of INCB057643 administered as monotherapy in fed state.	C2D1