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

Sponsor

Incyte Corporation (Industry)

Overall Status

Terminated

CT.gov ID

NCT02712905

Collaborator

(none)

116

Enrollment

Locations

Arms

71.3

Actual Duration (Months)

7.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors and Hematologic Malignancy	Drug: INCB059872 Drug: all-trans retinoic acid (ATRA) Drug: azacitidine Drug: nivolumab	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

116 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1/2, Open-Label, Dose-Escalation/Dose-Expansion, Safety and Tolerability Study of INCB059872 in Subjects With Advanced Malignancies

Actual Study Start Date :

May 5, 2016

Actual Primary Completion Date :

Apr 14, 2022

Actual Study Completion Date :

Apr 14, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: INCB059872	Drug: INCB059872 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.
Experimental: INCB059872 in combination with other therapies 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 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. Drug: all-trans retinoic acid (ATRA) Drug: azacitidine Drug: nivolumab

Arm

Intervention/Treatment

Experimental: INCB059872

Drug: INCB059872

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.

Experimental: INCB059872 in combination with other therapies

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

Outcome Measures

Primary Outcome Measures

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 [AEs assessed from screening through 30 days after end of treatment, up to 6 months]

Secondary Outcome Measures

Tumor response rates in subjects with measurable disease [Tumor response at protocol-defined intervals from baseline through end of treatment, up to approximately 6 months]
Maximum observed plasma concentration (Cmax) of INCB059872 [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]
Area under the single-dose plasma concentration-time curve (AUC0-t) of INCB059872 [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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama	Birmingham	Alabama	United States	35487
2	Moores UCSD Cancer Center	La Jolla	California	United States	92093
3	UCLA Medical Center	Los Angeles	California	United States	90095
4	Northwestern University	Chicago	Illinois	United States	60208
5	University of Kansas Center for Research, Inc.	Kansas City	Kansas	United States	66045
6	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
7	Columbia University	New York	New York	United States	10027
8	Oregon Health Science University	Portland	Oregon	United States	97297
9	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
10	Vanderbilt University	Nashville	Tennessee	United States	37240
11	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
12	Institut Jules Bordet	Brussel		Belgium
13	Netherland Cancer Institute	Amsterdam		Netherlands
14	VU Medical Center	Amsterdam		Netherlands
15	Erasmus MC	Rotterdam		Netherlands