Clinical trial NCT02712905: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
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
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2016-03-18
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of Participants Receiving INCB059872 Monotherapy With Any Treatment-emergent Adverse Event (TEAE)
timeFrame: up to 588 days
measure: Number of Participants Receiving INCB059872 Combination Therapy With Any TEAE
timeFrame: up to 1387 days
Secondary outcomes:
measure: Objective Response Rate (ORR) in Participants With the Indicated Type of Solid Tumors Who Received INCB059872 Monotherapy
timeFrame: up to 518 days
measure: ORR for Altering the Natural History of the Disease in Participants With Acute Myeloid Leukemia (AML) Who Received INCB059872 Monotherapy
timeFrame: up to 85 days
measure: ORR for Altering the Natural History of the Disease in Participants With Myelodysplastic Syndrome (MDS) Who Received INCB059872 Monotherapy
timeFrame: up to 61 days
measure: Change From Baseline in Spleen Volume Reduction (SVR) at Week 12 in Participants With Myelofibrosis (MF) Who Received INCB059872 Monotherapy
timeFrame: Baseline; Week 12
measure: Cmax of INCB059872 in Plasma When Received as Monotherapy
timeFrame: Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose
measure: Tmax of INCB059872 in Plasma When Received as Monotherapy
timeFrame: Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose
measure: AUC(0-τ) of INCB059872 in Plasma When Received as Monotherapy
timeFrame: Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose
measure: t1/2 of INCB059872 in Plasma When Received as Monotherapy
timeFrame: Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose
measure: CL/F of INCB059872 in Plasma When Received as Monotherapy
timeFrame: Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose
measure: ORR in Participants With SCLC Who Received Combination Therapy
timeFrame: up to 1353 days
measure: ORR for Altering the Natural History of the Disease in Participants With AML Who Received Combination Therapy
timeFrame: up to 208 days
measure: ORR for Altering the Natural History of the Disease in Participants With MDS Who Received Combination Therapy
timeFrame: up to 85 days
measure: Cmax of INCB059872 in Plasma When Received as Combination Therapy
timeFrame: Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose
measure: Tmax of INCB059872 in Plasma When Received as Combination Therapy
timeFrame: Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose
measure: AUC(0-τ) of INCB059872 in Plasma When Received as Combination Therapy
timeFrame: Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose
measure: t1/2 of INCB059872 in Plasma When Received as Combination Therapy
timeFrame: Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose
measure: CL/F of INCB059872 in Plasma When Received as Combination Therapy
timeFrame: Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: La Jolla
country: United States
facility: Moores UCSD Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Center for Research, Inc.
state: Kansas
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Portland
country: United States
facility: Oregon Health Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Brussel
country: Belgium
facility: Institut Jules Bordet
city: Amsterdam
country: Netherlands
facility: Netherland Cancer Institute
city: Amsterdam
country: Netherlands
facility: VU Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus MC
Study officials:
affiliation: Incyte Corporation
name: Fred Zheng, MD
role: STUDY_DIRECTOR
References: