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

Solid Tumors and Hematologic Malignancy Clinical Trial

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 Details — Status: Terminated

Administrative data

• NCT number: NCT02712905
• Other study ID #: INCB 59872-101
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: May 5, 2016
• Est. completion date: April 14, 2022

Study information

• Verified date: May 2023
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 116
• Est. completion date: April 14, 2022
• Est. primary completion date: April 14, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Neoplasms
• Solid Tumors and Hematologic Malignancy

Intervention

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.
• all-trans retinoic acid (ATRA)

• azacitidine

• nivolumab

Locations

Country	Name	City	State
Belgium	Institut Jules Bordet	Brussel
Netherlands	Netherland Cancer Institute	Amsterdam
Netherlands	VU Medical Center	Amsterdam
Netherlands	Erasmus MC	Rotterdam
United States	University of Alabama	Birmingham	Alabama
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Northwestern University	Chicago	Illinois
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of Kansas Center for Research, Inc.	Kansas City	Kansas
United States	Moores UCSD Cancer Center	La Jolla	California
United States	UCLA Medical Center	Los Angeles	California
United States	Vanderbilt University	Nashville	Tennessee
United States	Columbia University	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Oregon Health Science University	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  Belgium,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Objective Response Rate (ORR) in Participants With the Indicated Type of Solid Tumors Who Received INCB059872 Monotherapy	ORR was defined as the percentage of participants who achieved a best overall response of complete response (CR) or a partial response (PR), per investigator assessment according to Response Evaluation Criteria in Solid Tumors version 1.1 (RESIST v1.1), recorded before and including the first event of progressive disease (PD). CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions.	up to 518 days
Secondary	ORR for Altering the Natural History of the Disease in Participants With Acute Myeloid Leukemia (AML) Who Received INCB059872 Monotherapy	ORR was defined as the percentage of participants who achieved a best overall response of complete remission or complete remission with incomplete hematologic recovery (CRi), per the International Working Group Response Criteria for AML, recorded before and including the first event of progression (treatment failure, relapse, and PD) based on altering the natural history of the disease. Complete remission: absolute neutrophil count (ANC) =1.0 x 10^9/Liter (L), platelet count =100 x 10^9/L, bone marrow with less than 5% blast cells, Auer rods not detectable; no platelet, or whole blood transfusions for 7 days prior to the date of the hematology assessment. CRi: complete remission, but the ANC count may be < 1.0 x 10^9/L and/or the platelet count may be <100 x 10^9/L.	up to 85 days
Secondary	ORR for Altering the Natural History of the Disease in Participants With Myelodysplastic Syndrome (MDS) Who Received INCB059872 Monotherapy	ORR was defined as the percentage of participants who achieved a best overall response of complete remission, partial remission, or bone marrow complete remission, per the International Working Group Response Criteria for MDS, recorded before and including the first event of progression (treatment failure, relapse after CR or PR, disease transformation, and PD) based on altering the natural history of the disease. Complete remission: <5% bone marrow blasts without evidence of dysplasia; peripheral blood counts: hemoglobin =11 grams per deciliter (g/dL), neutrophils =1 x 10^9/L, platelets =100 x 10^9/L. Partial remission: meeting complete remission criteria, but bone marrow blasts decreased by =50% from pre-treatment, but still =5%. Bone marrow complete remission: =5% bone marrow blasts and decrease by =50% from pre-treatment.	up to 61 days
Secondary	Change From Baseline in Spleen Volume Reduction (SVR) at Week 12 in Participants With Myelofibrosis (MF) Who Received INCB059872 Monotherapy	Change from Baseline was to have been calculated as the post-Baseline value minus the Baseline value. SVR was to have been measured by magnetic resonance imaging (MRI), or by computed tomography (CT) scan in participants who were not candidates for MRI or when MRI was not readily available.	Baseline; Week 12
Secondary	Cmax of INCB059872 in Plasma When Received as Monotherapy	Cmax was defined as the maximum observed plasma concentration of INCB059872.	Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose
Secondary	Tmax of INCB059872 in Plasma When Received as Monotherapy	tmax was defined as the time to the maximum observed plasma concentration of INCB059872.	Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose
Secondary	AUC(0-t) of INCB059872 in Plasma When Received as Monotherapy	AUC(0-t) was defined as the area under the plasma concentration-time curve from time = 0 to the end of the dosing period of INCB059872.	Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose
Secondary	t1/2 of INCB059872 in Plasma When Received as Monotherapy	t1/2 was defined as the half-life of INCB059872.	Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose
Secondary	CL/F of INCB059872 in Plasma When Received as Monotherapy	CL/F was defined as the apparent oral clearance of INCB059872.	Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose
Secondary	ORR in Participants With SCLC Who Received Combination Therapy	ORR was defined as the percentage of participants who achieved a best overall response of CR or a PR, per investigator assessment according to RESIST v1.1, recorded before and including the first event of PD. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions.	up to 1353 days
Secondary	ORR for Altering the Natural History of the Disease in Participants With AML Who Received Combination Therapy	ORR was defined as the percentage of participants who achieved a best overall response of complete remission or CRi, per the International Working Group Response Criteria for AML, recorded before and including the first event of progression (treatment failure, relapse, and PD) based on altering the natural history of the disease. Complete remission: ANC =1.0 x 10^9/L, platelet count =100 x 10^9/L, bone marrow with less than 5% blast cells, Auer rods not detectable; no platelet, or whole blood transfusions for 7 days prior to the date of the hematology assessment. CRi: complete remission, but the ANC count may be < 1.0 x 10^9/L and/or the platelet count may be <100 x 10^9/L.	up to 208 days
Secondary	ORR for Altering the Natural History of the Disease in Participants With MDS Who Received Combination Therapy	ORR was defined as the percentage of participants who achieved a best overall response of complete remission, partial remission, or bone marrow complete remission, per the International Working Group Response Criteria for MDS, recorded before and including the first event of progression (treatment failure, relapse after CR or PR, disease transformation, and PD) based on altering the natural history of the disease. Complete remission: <5% bone marrow blasts without evidence of dysplasia; peripheral blood counts: hemoglobin =11 g/dL, neutrophils =1 x 10^9/L, platelets =100 x 10^9/L. Partial remission: meeting complete remission criteria, but bone marrow blasts decreased by =50% from pre-treatment, but still =5%. Bone marrow complete remission: =5% bone marrow blasts and decrease by =50% from pre-treatment.	up to 85 days
Secondary	Cmax of INCB059872 in Plasma When Received as Combination Therapy	Cmax was defined as the maximum observed plasma concentration of INCB059872.	Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose
Secondary	Tmax of INCB059872 in Plasma When Received as Combination Therapy	tmax was defined as the time to the maximum observed plasma concentration of INCB059872.	Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose
Secondary	AUC(0-t) of INCB059872 in Plasma When Received as Combination Therapy	AUC(0-t) was defined as the area under the plasma concentration-time curve from time = 0 to the end of the dosing period of INCB059872.	Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose
Secondary	t1/2 of INCB059872 in Plasma When Received as Combination Therapy	t1/2 was defined as the half-life of INCB059872.	Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose
Secondary	CL/F of INCB059872 in Plasma When Received as Combination Therapy	CL/F was defined as the apparent oral clearance of INCB059872.	Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose