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

• ClinicalTrials.gov Identifier: NCT02711137
• Recruitment Status: Terminated
• First Posted: March 17, 2016
• Last Update Posted: November 14, 2019
• Sponsor: Incyte Corporation
• Information provided by (Responsible Party): Incyte Corporation

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Solid Tumors	Drug: INCB057643; Drug: Gemcitabine; Drug: Paclitaxel; Drug: Rucaparib; Drug: Abiraterone; Drug: Ruxolitinib; Drug: Azacitidine	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 136 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2, Open-Label, Dose-Escalation/Dose-Expansion, Safety and Tolerability Study of INCB057643 in Subjects With Advanced Malignancies
• Study Start Date: May 2016
• Actual Primary Completion Date: February 13, 2019
• Actual Study Completion Date: February 13, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: INCB057643	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).
Experimental: INCB057643 + Standard of Care (SOC) agents	Drug: INCB057643; Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 3), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 4).; Drug: Gemcitabine; Standard of Care (SOC) agents; Drug: Paclitaxel; Standard of Care (SOC) agents; Drug: Rucaparib; Standard of Care (SOC) agents; Drug: Abiraterone; Standard of Care (SOC) agents; Drug: Ruxolitinib; Standard of Care (SOC) agents; Drug: Azacitidine; Standard of Care (SOC) agents

Outcome Measures

Primary Outcome Measures :

1. Safety and tolerability of INCB057643 as monotherapy and in combination with standard of care (SOC) agents in patients with advanced malignancies; assessed by clinical laboratory assessments, physical examinations, 12 lead ECGs, and adverse events (AEs) [ Time Frame: From screening through at least 30 days after end of treatment, up to approximately 24 months ]

Secondary Outcome Measures :

1. Pharmacokinetics of INCB057643 as monotherapy in the fasted state and in the fed state (food effect; Part 2 only) and when administered in combination with Standard of Care (SOC) agents in the fasted state assessed by plasma and urine concentrations [ Time Frame: Protocol-defined timepoints in treatment Cycle 1 and 2, up to approximately 1 month. ]
2. Measurement of cellular myc protein concentrations before and after administration of INCB057643 when administered as monotherapy [ Time Frame: PD in plasma at pre-dose and 0.5, 1, 2, 4, 6 and 8 hours postdose, up to approximately 1 month. ]
3. Efficacy of INCB057643 when administered as monotherapy and in combination with SOC agents based on the investigator assessment of response using criteria appropriate for each disease in subjects with advanced malignancies criteria [ Time Frame: Efficacy measures from screening through end of treatment and follow-up (every 9 weeks), up to approximately 24 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Alabama

University of Alabama

Birmingham, Alabama, United States, 35294-3300

United States, California

University of California

La Jolla, California, United States, 92093

United States, Colorado

Sarah Cannon Research Institute at Health One

Denver, Colorado, United States, 80218

United States, Connecticut

Yale University

New Haven, Connecticut, United States, 06510

United States, Florida

Sylvester Comprehensive Cancer Center

Miami, Florida, United States, 33136

Hematology - Oncology Associates of Treasure Coast

Port Saint Lucie, Florida, United States, 34952

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48109

United States, Minnesota

University of Minnesota

Minneapolis, Minnesota, United States, 55455

United States, Missouri

Washington University

Saint Louis, Missouri, United States, 63110

United States, New York

University of Rochester, Wilmot Cancer Center

Rochester, New York, United States, 14642

United States, North Carolina

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States, 27599

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States, 27157

United States, Texas

Oncology Consultants, P.A.

Houston, Texas, United States, 77030

The Methodist Hospital

Houston, Texas, United States, 77030

United States, Utah

Huntsman Cancer Institute

Salt Lake City, Utah, United States, 84112

United States, Washington

MultiCare Institute for Research and Innovation

Tacoma, Washington, United States, 98405

Belgium

Institut Jules Bordet, Clinical Trial Conduct Unit

Brussels, Belgium, B-1000

France

HÔPITAL SAINT-LOUIS, Service Hématologie Adultes

Paris, France, 75010

Sponsors and Collaborators

Incyte Corporation

Investigators

• Study Director: Fred Zheng, MD, PhD; Incyte Corporation

More Information

• Responsible Party: Incyte Corporation
• ClinicalTrials.gov Identifier: NCT02711137 History of Changes
• Other Study ID Numbers: INCB 57643-101
• First Posted: March 17, 2016
• Last Update Posted: November 14, 2019
• Last Verified: November 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Incyte Corporation:

Solid tumor; lymphoma; leukemia; AML; myelodysplastic syndrome (MDS); multiple myeloma; myeloproliferative neoplasm (MPN); MDS/MPN; myelofibrosis (MF); pancreatic cancer; colorectal cancer; non-small cell lung cancer; prostate cancer; breast cancer; ovarian cancer; glioblastoma multiforme (GBM); NUT midline carcinoma; non-Hodgkin lymphoma; diffuse large B-cell lymphoma (DLBCL); double-hit; triple-hit; myc; bromodomain and extra-terminal (BET) inhibitor

Additional relevant MeSH terms:

Neoplasms; Gemcitabine; Azacitidine; Rucaparib; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Poly(ADP-ribose) Polymerase Inhibitors