An Open-Label, Dose-Escalation/Dose-Expansion Safety Study of INCB059872 in Subjects With Advanced Malignancies

NCT02712905 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: INCB 59872-1012017-001710-28
• Study Type: interventional
• Target: 116
• Locations: 3 countries
• Sites: 15

Brief Summary

This is an open-label, dose-escalation/dose-expansion study of INCB059872 in subjects with advanced malignancies. The study will be conducted in 4 parts. Part 1 (mono therapy dose escalation) will determine the recommended dose(s) of INCB059872 for dose expansion, based on maximum tolerated dose and/or a tolerated pharmacologically active dose. Part 2 (dose expansion) will further determine the safety, tolerability, efficacy, PK, and PD of the selected monotherapy dose(s) in AML/MDS, SCLC, myelofibrosis, Ewing sarcoma, and poorly differentiated neuroendocrine tumors. Part 3 will determine the recommended dose(s) of INCB059872 in combination with azacitadine and all-trans retinoic acid in AML and in combination with nivolumab in SCLC. Part 4 will further determine the safety, tolerability, efficacy, PK, and PD of the selected combination dose(s) in Part 3.

Conditions

Solid Tumors and Hematologic Malignancy

Keywords

Acute myeloid leukemia (AML); myelodysplastic syndrome (MDS); small cell lung cancer (SCLC); myelofibrosis (MF); solid tumor, lysine-specific demethylase 1 (LSD1) inhibitor

Outcome Measures

Primary Outcomes (2)

• Number of Participants Receiving INCB059872 Monotherapy With Any Treatment-emergent Adverse Event (TEAE)

  Adverse events (AEs) were defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study drug(s). TEAEs were defined as AEs either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug.

  up to 588 days

• Number of Participants Receiving INCB059872 Combination Therapy With Any TEAE

  AEs were defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study drug(s). TEAEs were defined as AEs either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug.

  up to 1387 days

Secondary Outcomes (17)

• Objective Response Rate (ORR) in Participants With the Indicated Type of Solid Tumors Who Received INCB059872 Monotherapy

  up to 518 days

• ORR for Altering the Natural History of the Disease in Participants With Acute Myeloid Leukemia (AML) Who Received INCB059872 Monotherapy

  up to 85 days

• ORR for Altering the Natural History of the Disease in Participants With Myelodysplastic Syndrome (MDS) Who Received INCB059872 Monotherapy

  up to 61 days

• Change From Baseline in Spleen Volume Reduction (SVR) at Week 12 in Participants With Myelofibrosis (MF) Who Received INCB059872 Monotherapy

  Baseline; Week 12

• Cmax of INCB059872 in Plasma When Received as Monotherapy

  Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose

Study Arms (2)

INCB059872

EXPERIMENTAL

Drug: INCB059872

INCB059872 in combination with other therapies

EXPERIMENTAL

Initial cohort dose of INCB059872 to evaluate different doses of INCB0599872 in combination with other therapies in the following treatment groups: * Combination with all-trans retinoic acid (ATRA) in subjects with relapsed/refractory AML. * Combination with azacitidine in subjects with newly diagnosed, treatment-naive AML * Combination with nivolumab in subjects with advanced SCLC previously progressed on platinum-based treatment. Upon identification of the recommended dose(s) for each treatment combination, expansion cohorts of approximately 30 subjects in each treatment group may begin enrollment to further determine safety, tolerability, efficacy, PK, and PD of the selected dose(s).

Drug: INCB059872; Drug: all-trans retinoic acid (ATRA); Drug: azacitidine; Drug: nivolumab

Interventions

INCB059872 DRUG

Initial cohort dose of INCB059872 monotherapy at the protocol-specified starting dose, with subsequent cohort escalations based on protocol-specific criteria. The recommended dose(s) will be taken forward into expansion cohorts. INCB059872 tablets to be administered by mouth.

INCB059872; INCB059872 in combination with other therapies

all-trans retinoic acid (ATRA) DRUG

INCB059872 in combination with other therapies

azacitidine DRUG

INCB059872 in combination with other therapies

nivolumab DRUG

INCB059872 in combination with other therapies

Eligibility Criteria

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

You may qualify if:

• Male or female subjects, age 18 years or older.
• Presence of measurable disease that has been confirmed by histology or cytology.
• Must not be a candidate for potentially curative therapy or standard-of-care approved therapy
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.

You may not qualify if:

• Receipt of anticancer medications, anticancer therapies, or investigational drugs within the defined interval before the first administration of study drug.
• Any unresolved toxicity ≥ Grade 2 from previous anticancer therapy except for stable chronic toxicities (≤ Grade 2) not expected to resolve.
• Laboratory and medical history parameters outside Protocol-defined range.
• Known additional malignancy that is progressing or requires active treatment.

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (15)

University of Alabama

Birmingham, Alabama, 35487, United States

Location

Moores UCSD Cancer Center

La Jolla, California, 92093, United States

Location

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Northwestern University

Chicago, Illinois, 60208, United States

Location

University of Kansas Center for Research, Inc.

Kansas City, Kansas, 66045, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Columbia University

New York, New York, 10027, United States

Location

Oregon Health Science University

Portland, Oregon, 97297, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University

Nashville, Tennessee, 37240, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Institut Jules Bordet

Brussels, Belgium

Location

Netherland Cancer Institute

Amsterdam, Netherlands

Location

VU Medical Center

Amsterdam, Netherlands

Location

Erasmus MC

Rotterdam, Netherlands

Location

MeSH Terms

Conditions

Hematologic Neoplasms; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Small Cell Lung Carcinoma; Primary Myelofibrosis

Interventions

INCB059872; Tretinoin; Azacitidine; Nivolumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Bone Marrow Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Myeloproliferative Disorders

Intervention Hierarchy (Ancestors)

Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors; Aza Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The study was terminated by the sponsor due to a strategic business decision.

Results Point of Contact

• Title: Study Director
• Organization: Incyte Corporation

medinfo@incyte.com

1-855-463-3463

Study Officials

• Fred Zheng, MD

  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: February 18, 2016
• First Posted: March 18, 2016
• Study Start: May 5, 2016
• Primary Completion: April 14, 2022
• Study Completion: April 14, 2022
• Last Updated: November 4, 2025
• Results First Posted: June 12, 2023

Record last verified: 2025-10

Locations

US (11); BE (1); NL (3)