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

NCT02711137 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: INCB 57643-1012017-002641-29
• Study Type: interventional
• Target: 137
• Locations: 3 countries
• Sites: 18

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.

Conditions

Solid Tumors

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Percent Inhibition of Total Cellular Myc Protein Concentrations Before and After Administration of INCB057643 When Administered as Monotherapy in an Ex-vivo Assay

  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

• Objective Response Rate (ORR) With INCB057643 in Solid Tumors

  Efficacy measures from screening through end of treatment and follow-up (every 9 weeks), up to approximately 24 months

• Cmax: Maximum Observed Plasma Concentration of INCB057643.

  Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D1 and C1D8

• Tmax: Time to Maximum Plasma Concentration of INCB057643

  Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D1 and C1D8

• AUC0-t: Area Under the Single-dose Plasma Concentration-time Curve of INCB057643

  Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D1

Study Arms (14)

Part1/Treatment Group A : 8mg QD INCB057643

EXPERIMENTAL

Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA. Treatment Group A included solid tumors and lymphoma

Drug: INCB057643

Part1/Treatment Group A : 12mg QD INCB057643

EXPERIMENTAL

Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA. Treatment Group A included solid tumors and lymphoma

Drug: INCB057643

Part1/Treatment Group A : 16mg QD INCB057643

EXPERIMENTAL

Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA. Treatment Group A included solid tumors and lymphoma

Drug: INCB057643

Part1/Treatment Group B : 8mg QD INCB057643

EXPERIMENTAL

Initial cohort dose of INCB054763 monotherapy at the protocol-specified cohort escalation treatment group B (TGB), based on protocol-specific criteria. Treatment Group B included any acute leukemia, HRMDS, MDS/MPN, or MF

Drug: INCB057643

Part1/Treatment Group B : 12mg QD INCB057643

EXPERIMENTAL

Initial cohort dose of INCB054763 monotherapy at the protocol-specified cohort escalation treatment group B (TGB), based on protocol-specific criteria. Treatment Group B included any acute leukemia, HRMDS, MDS/MPN, or MF.

Drug: INCB057643

Part1/Treatment Group C : 8mg QD INCB057643

EXPERIMENTAL

Initial cohort dose of INCB054763 monotherapy at the protocol-specified cohort escalation treatment group C (TGC), based on protocol-specific criteria. Treatment Group C includes subjects with MM

Drug: INCB057643

Part2/Treatment Group A : 12 mg INCB057643 Expansion Cohort

EXPERIMENTAL

Initial cohort dose of INCB054763 monotherapy at the specified RP2D dose selected in Part 1 cohort escalation treatment group A (TGA), based on protocol-specific criteria. Part 2 Treatment Group A expansion included pancreatic adenocarcinoma, castration-resistant prostrate cancer, breast cancer, high grade serious ovarian cancer, glioblastoma multiform, non-hodgkin's lymphoma, ewing's sarcoma, and solid tumor or lymphoma.

Drug: INCB057643

Part2/Treatment Group B : 12 mg INCB057643 Expansion Cohort

EXPERIMENTAL

Initial cohort dose of INCB057463 monotherapy at the specified RP2D dose selected in Part 1 cohort escalation treatment group B (TGB), based on protocol-specific criteria. Part 2 Treatment Group B expansion included pancreatic adenocarcinoma, castration-resistant prostrate cancer, breast cancer, high grade serious ovarian cancer, glioblastoma multiform, non-hodgkin's lymphoma, ewing's sarcoma, and solid tumor or lymphoma.

Drug: INCB057643

Part3/Treatment Group A : 8 mg INCB057643 + Gemcitabine 1000mg

EXPERIMENTAL

Initial cohort dose of INCB057643 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Gemcitabine) in relapsed or refractory advanced or metastatic solid tumors and hematologic malignancies where Gemcitabine is relevant

Drug: INCB057643; Drug: Gemcitabine

Part3/Treatment Group B : 8 mg INCB057643 + Paclitaxel 80mg

EXPERIMENTAL

Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Paclitaxel) in relapsed or refractory advanced or metastatic solid tumors and hematologic malignancies.

Drug: INCB057643; Drug: Paclitaxel

Part3/Treatment Group C : 8 mg INCB057643 + Rucaparib 600mg

EXPERIMENTAL

Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Rucaparib) in relapsed or refractory advanced or metastatic solid tumors and hematologic malignancies.

Drug: INCB057643; Drug: Rucaparib

Part3/Treatment Group D : 8 mg INCB057643 + Abir +Predni

EXPERIMENTAL

Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Abiraterone + Prednisone) in Castration Resistant Prostrate Cancer

Drug: INCB057643; Drug: Abiraterone

Part3/Treatment Group E : 8 mg INCB057643 + Ruxolitinib 20mg

EXPERIMENTAL

Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Ruxolitinib) in Myelofibrosis.

Drug: INCB057643; Drug: Ruxolitinib

Part3/Treatment Group F : 8 mg INCB057643 + Azacitidine 75mg

EXPERIMENTAL

Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Azacitidine) in Acute Myeloid Leukemia and Myelodysplastic Syndrome

Drug: INCB057643; Drug: Azacitidine

Interventions

INCB057643 DRUG

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).

Part1/Treatment Group A : 12mg QD INCB057643; Part1/Treatment Group A : 16mg QD INCB057643; Part1/Treatment Group A : 8mg QD INCB057643; Part1/Treatment Group B : 12mg QD INCB057643; Part1/Treatment Group B : 8mg QD INCB057643; Part1/Treatment Group C : 8mg QD INCB057643; Part2/Treatment Group A : 12 mg INCB057643 Expansion Cohort; Part2/Treatment Group B : 12 mg INCB057643 Expansion Cohort; Part3/Treatment Group A : 8 mg INCB057643 + Gemcitabine 1000mg; Part3/Treatment Group B : 8 mg INCB057643 + Paclitaxel 80mg; Part3/Treatment Group C : 8 mg INCB057643 + Rucaparib 600mg; Part3/Treatment Group D : 8 mg INCB057643 + Abir +Predni; Part3/Treatment Group E : 8 mg INCB057643 + Ruxolitinib 20mg; Part3/Treatment Group F : 8 mg INCB057643 + Azacitidine 75mg

Gemcitabine DRUG

Standard of Care (SOC) agents

Part3/Treatment Group A : 8 mg INCB057643 + Gemcitabine 1000mg

Paclitaxel DRUG

Standard of Care (SOC) agents

Part3/Treatment Group B : 8 mg INCB057643 + Paclitaxel 80mg

Rucaparib DRUG

Standard of Care (SOC) agents

Part3/Treatment Group C : 8 mg INCB057643 + Rucaparib 600mg

Abiraterone DRUG

Standard of Care (SOC) agents

Part3/Treatment Group D : 8 mg INCB057643 + Abir +Predni

Ruxolitinib DRUG

Standard of Care (SOC) agents

Part3/Treatment Group E : 8 mg INCB057643 + Ruxolitinib 20mg

Azacitidine DRUG

Standard of Care (SOC) agents

Part3/Treatment Group F : 8 mg INCB057643 + Azacitidine 75mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (18)

University of Alabama

Birmingham, Alabama, 35294-3300, United States

Location

University of California

La Jolla, California, 92093, United States

Location

Sarah Cannon Research Institute at Health One

Denver, Colorado, 80218, United States

Location

Yale University

New Haven, Connecticut, 06510, United States

Location

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Hematology - Oncology Associates of Treasure Coast

Port Saint Lucie, Florida, 34952, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

University of Rochester, Wilmot Cancer Center

Rochester, New York, 14642, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

Oncology Consultants, P.A.

Houston, Texas, 77030, United States

Location

The Methodist Hospital

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MultiCare Institute for Research and Innovation

Tacoma, Washington, 98405, United States

Location

Institut Jules Bordet, Clinical Trial Conduct Unit

Brussels, B-1000, Belgium

Location

HÔPITAL SAINT-LOUIS, Service Hématologie Adultes

Paris, 75010, France

Location

Related Publications (1)

• 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.

  PMID: 31527168 DERIVED

MeSH Terms

Conditions

Lymphoma; Leukemia; Myelodysplastic Syndromes; Multiple Myeloma; Myeloproliferative Disorders; Primary Myelofibrosis; Pancreatic Neoplasms; Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung; Prostatic Neoplasms; Breast Neoplasms; Ovarian Neoplasms; Glioblastoma; Lymphoma, Non-Hodgkin; Lymphoma, Large B-Cell, Diffuse

Interventions

INCB057643; Gemcitabine; Paclitaxel; rucaparib; abiraterone; ruxolitinib; Azacitidine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hematologic Diseases; Bone Marrow Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Neoplasms, Female; Gonadal Disorders; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Lymphoma, B-Cell

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Aza Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Study Director
• Organization: Incyte Corporation

medinfo@incyte.com

1-855-463-3463

Study Officials

• Fred Zheng, MD, PhD

  Incyte Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2016
• First Posted: March 17, 2016
• Study Start: May 18, 2016
• Primary Completion: February 13, 2019
• Study Completion: February 13, 2019
• Last Updated: October 21, 2025
• Results First Posted: April 28, 2022

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (16); BE (1); FR (1)