Clinical Trials /

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

NCT02712905

Description:

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.

Related Conditions:
  • Hematopoietic and Lymphoid Malignancy
  • Malignant Solid Tumor
  • Small Cell Lung Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: An Open-Label, Dose-Escalation/Dose-Expansion Safety Study of INCB059872 in Subjects With Advanced Malignancies
  • Official Title: A Phase 1/2, Open-Label, Dose-Escalation/Dose-Expansion, Safety and Tolerability Study of INCB059872 in Subjects With Advanced Malignancies

Clinical Trial IDs

  • ORG STUDY ID: INCB 59872-101
  • NCT ID: NCT02712905

Conditions

  • Solid Tumors and Hematologic Malignancy

Interventions

DrugSynonymsArms
INCB059872INCB059872
all-trans retinoic acid (ATRA)INCB059872 in combination with other therapies
azacitidineINCB059872 in combination with other therapies
nivolumabINCB059872 in combination with other therapies

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
INCB059872Experimental
  • INCB059872
INCB059872 in combination with other therapiesExperimentalInitial 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).
  • INCB059872
  • all-trans retinoic acid (ATRA)
  • azacitidine
  • nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  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.

        Exclusion Criteria:

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability of INCB059872 in monotherapy and in combination with other therapies as measured by the frequency, duration, and severity of adverse events (AEs) in participants, and determine recommended dose(s) for further study
Time Frame:AEs assessed from screening through 30 days after end of treatment, up to 6 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Tumor response rates in subjects with measurable disease
Time Frame:Tumor response at protocol-defined intervals from baseline through end of treatment, up to approximately 6 months
Safety Issue:
Description:
Measure:Maximum observed plasma concentration (Cmax) of INCB059872
Time Frame:0.5, 1, 2, 4, 6 hours postdose on Days 1 and 15 in treatment Cycle 1 and for food effect in Cycle 2, up to approximately 1 month
Safety Issue:
Description:
Measure:Area under the single-dose plasma concentration-time curve (AUC0-t) of INCB059872
Time Frame:0.5, 1, 2, 4, 6 hours postdose on Days 1 and 15 in treatment Cycle 1 and for food effect in Cycle 2, up to approximately 1 month
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Incyte Corporation

Trial Keywords

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

Last Updated

August 28, 2019