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.
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
| Drug | Synonyms | Arms |
|---|
| INCB059872 | | INCB059872 |
| all-trans retinoic acid (ATRA) | | INCB059872 in combination with other therapies |
| azacitidine | | INCB059872 in combination with other therapies |
| nivolumab | | INCB059872 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
| Name | Type | Description | Interventions |
|---|
| INCB059872 | Experimental | | |
| 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). | - 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: | Terminated |
| 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
April 22, 2021
