Neoplasms

Blood and Lymph Conditions

All Conditions

Hematologic Neoplasms

Hematologic Diseases

INCB024360: 25 mg and 100 mg tablets Doses will be escalated in accordance with the dosing schedule.

INCB024360

Lance Leopold, MD

This is an open label, dose escalation study using a 3 + 3 design to determine if INCB024360 (study drug) is safe, well-tolerated and effective in patients with advanced malignancies. Patients will be enrolled and treated in cohorts of three and each observed a minimum of 28 days before the next group is enrolled and may begin to receive study drug. For subject safety, the first subject in each cohort will be administered drug for one week before the next two subjects in the cohort can begin drug administration. Doses will be escalated unless a dose-limiting toxicity (DLT) is observed in one of three subjects.

An expanded cohort of up to 15 patients may be recruited to further explore safety at the 'maximum tolerated dose' or at a lower, pharmacologically active, dose.

A Dose-escalation Study in Subjects With Advanced Malignancies

A Phase I, Open-Label, Dose-Escalation Study to Determine the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of INCB024360 in Patients With Advanced Malignancies

Incyte Corporation

Symptoms and General Pathology

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Small Cell Lung Carcinoma

Preleukemia

Myelodysplastic Syndromes

Lung Neoplasms

Primary Myelofibrosis

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Small Cell Lung Cancer

Acute Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Dermatologic Agents

Amino Acids

Nivolumab

Tretinoin

Azacitidine

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Antimetabolites

Enzyme Inhibitors

Keratolytic Agents

Lysine

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).

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.

INCB059872

all-trans retinoic acid (ATRA)

azacitidine

nivolumab

Fred Zheng, MD

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.

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

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

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.

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.

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.

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.

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.

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.

Cmax was defined as the maximum observed plasma concentration of INCB059872.

tmax was defined as the time to the maximum observed plasma concentration of INCB059872.

AUC(0-τ) was defined as the area under the plasma concentration-time curve from time = 0 to the end of the dosing period of INCB059872.

t1/2 was defined as the half-life of INCB059872.

CL/F was defined as the apparent oral clearance of INCB059872.

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.

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.

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.

Treatment-emergent adverse events, defined as adverse events 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, have been reported for the Safety Population.

Participants with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) received INB059872 2 milligrams (mg) as monotherapy once every other day (QOD) on a 28-day continuous therapy cycle.

Group A: INCB059872 Monotherapy; 2 mg QOD

Participants with AML or MDS received INB059872 2 mg as monotherapy once daily (QD) on a 28-day continuous therapy cycle.

Group A: INCB059872 Monotherapy; 2 mg QD

Participants with AML or MDS received INB059872 3 mg as monotherapy QOD on a 28-day continuous therapy cycle.

Group A: INCB059872 Monotherapy; 3 mg QOD

Participants with AML or MDS received INB059872 3 mg as monotherapy QD on a 28-day continuous therapy cycle.

Group A: INCB059872 Monotherapy; 3 mg QD

Participants with AML or MDS received INB059872 4 mg as monotherapy QD on a 28-day continuous therapy cycle.

Group A: INCB059872 Monotherapy; 4 mg QD

Participants with AML or MDS received INB059872 5 mg as monotherapy QD on a 28-day continuous therapy cycle.

Group A: INCB059872 Monotherapy; 5 mg QD

Participants with small cell lung cancer (SCLC) and other solid malignancies (e.g., endocrine tumors) received INB059872 1 mg as monotherapy QD on a 28-day continuous therapy cycle.

Group B: INCB059872 Monotherapy; 1 mg QD

Participants with SCLC and other solid malignancies (e.g., endocrine tumors) received INB059872 2 mg as monotherapy QOD on a 28-day continuous therapy cycle.

Group B: INCB059872 Monotherapy; 2 mg QOD

Participants with SCLC and other solid malignancies (e.g., endocrine tumors) received INB059872 2 mg as monotherapy QD on a 28-day continuous therapy cycle.

Group B: INCB059872 Monotherapy; 2 mg QD

Participants with SCLC and other solid malignancies (e.g., endocrine tumors) received INB059872 3 mg as monotherapy QOD on a 28-day continuous therapy cycle.

Group B: INCB059872 Monotherapy; 3 mg QOD

Participants with SCLC and other solid malignancies (e.g., endocrine tumors) received INB059872 3 mg as monotherapy QD on a 28-day continuous therapy cycle.

Group B: INCB059872 Monotherapy; 3 mg QD

Participants with SCLC and other solid malignancies (e.g., endocrine tumors) received INB059872 4 mg as monotherapy QOD on a 28-day continuous therapy cycle.

Group B: INCB059872 Monotherapy; 4 mg QOD

Participants with relapsed/refractory AML received INCB059872 2 mg QD in combination with all-trans retinoic acid (ATRA) (at a starting dose of 45 mg/meters squared \[m\^2\] per day at 2 evenly divided doses) on a 28-day continuous therapy cycle.

Group C: Combination Therapy; INCB059872 2 mg QD + ATRA

Participants with relapsed/refractory AML received oral INCB059872 3 mg QD in combination with ATRA (at a starting dose of 45 mg/m\^2 per day at 2 evenly divided doses) on a 28-day continuous therapy cycle.

Group C: Combination Therapy; INCB059872 3 mg QD + ATRA

Participants with relapsed/refractory AML received oral INCB059872 4 mg QD in combination with ATRA (at a starting dose of 45 mg/m\^2 per day at 2 evenly divided doses) on a 28-day continuous therapy cycle.

Group C: Combination Therapy; INCB059872 4 mg QD + ATRA

Participants with newly diagnosed, treatment-naïve AML or MDS received INCB059872 2 mg QD on a 28-day continuous therapy cycle in combination with azacitidine, administered at a starting dose of 75 mg/m\^2 subcutaneously or intravenously for 7 days during the first 9-day period of each 28-day treatment cycle.

Group D: Combination Therapy; INCB059872 2 mg QD + Azacitidine

Participants with newly diagnosed, treatment-naïve AML or MDS received INCB059872 3 mg QD on a 28-day continuous therapy cycle in combination with azacitidine, administered at a starting dose of 75 mg/m\^2 subcutaneously or intravenously for 7 days during the first 9-day period of each 28-day treatment cycle.

Group D: Combination Therapy; INCB059872 3 mg QD + Azacitidine

Participants with SCLC received oral INCB059872 3 mg QOD on a 28-day continuous therapy cycle in combination with nivolumab, administered at 3 mg/kilogram (kg) intravenously over 60 minutes every 2 weeks of each 28-day treatment cycle.

Group E: Combination Therapy; INCB059872 3 mg QOD + Nivolumab

Participants with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) received oral INB059872 2 milligrams (mg) as monotherapy once every other day (QOD) on a 28-day continuous therapy cycle.

Participants with AML or MDS received oral INB059872 2 mg as monotherapy once daily (QD) on a 28-day continuous therapy cycle.

Participants with AML or MDS received oral INB059872 3 mg as monotherapy QOD on a 28-day continuous therapy cycle.

Participants with AML or MDS received oral INB059872 3 mg as monotherapy QD on a 28-day continuous therapy cycle.

Participants with AML or MDS received oral INB059872 4 mg as monotherapy QD on a 28-day continuous therapy cycle.

Participants with AML or MDS received oral INB059872 5 mg as monotherapy QD on a 28-day continuous therapy cycle.

Participants with small cell lung cancer (SCLC) and other solid malignancies (e.g., endocrine tumors) received oral INB059872 1 mg as monotherapy QD on a 28-day continuous therapy cycle.

Participants with SCLC and other solid malignancies (e.g., endocrine tumors) received oral INB059872 2 mg as monotherapy QOD on a 28-day continuous therapy cycle.

Participants with SCLC and other solid malignancies (e.g., endocrine tumors) received oral INB059872 2 mg as monotherapy QD on a 28-day continuous therapy cycle.

Participants with SCLC and other solid malignancies (e.g., endocrine tumors) received oral INB059872 3 mg as monotherapy QOD on a 28-day continuous therapy cycle.

Participants with SCLC and other solid malignancies (e.g., endocrine tumors) received oral INB059872 3 mg as monotherapy QD on a 28-day continuous therapy cycle.

Participants with SCLC and other solid malignancies (e.g., endocrine tumors) received oral INB059872 4 mg as monotherapy QOD on a 28-day continuous therapy cycle.

Participants with relapsed/refractory AML received oral INCB059872 2 mg QD in combination with all-trans retinoic acid (ATRA) (at a starting dose of 45 mg/meters squared \[m\^2\] per day at 2 evenly divided doses) on a 28-day continuous therapy cycle.

Total

Age, Continuous

For treatment arms in which a single participant was enrolled, data have not been reported due to privacy concerns (denoted Number Analyzed=0 for treatment arm).

Sex: Female, Male

Ethnicity (NIH/OMB)

White

Black or African American

Asian

American-Indian/Alaska Native

Non-White

Unknown/Not Specified

Declined to Report

Race/Ethnicity, Customized

The study was terminated by the sponsor due to a strategic business decision.

Study Director

Safety Population: all enrolled participants who received at least 1 dose of INCB059872, ATRA, azacitidine, or nivolumab

Number of Participants Receiving INCB059872 Monotherapy With Any Treatment-emergent Adverse Event (TEAE)

Number of Participants Receiving INCB059872 Combination Therapy With Any TEAE

SCLC

Ewing's sarcoma

Poorly differentiated neuroendocrine tumors

Other solid tumors

Full Analysis Set: all enrolled participants who received at least 1 dose of INCB059872, ATRA, azacitidine, or nivolumab. Only participants with the indicated type of solid tumor who received monotherapy were analyzed.

Objective Response Rate (ORR) in Participants With the Indicated Type of Solid Tumors Who Received INCB059872 Monotherapy

Full Analysis Set. Only participants with AML who received monotherapy were analyzed. The participant in Group A receiving 3 mg QOD was on treatment for less than a week and therefore was not evaluated for efficacy.

ORR for Altering the Natural History of the Disease in Participants With Acute Myeloid Leukemia (AML) Who Received INCB059872 Monotherapy

Full Analysis Set. Only participants with MDS who received monotherapy were analyzed. The participant in Group A receiving 3 mg QOD was on treatment for less than a week and therefore was not evaluated for efficacy.

ORR for Altering the Natural History of the Disease in Participants With Myelodysplastic Syndrome (MDS) Who Received INCB059872 Monotherapy

Full Analysis Set. Analysis was not conducted because no participants with MF remained in the study at Week 12.

Change From Baseline in Spleen Volume Reduction (SVR) at Week 12 in Participants With Myelofibrosis (MF) Who Received INCB059872 Monotherapy

Pharmacokinetic (PK)-Evaluable Population: all participants who received at least 1 dose of study treatment and provided at least 1 postdose PK sample

Cmax of INCB059872 in Plasma When Received as Monotherapy

Pharmacokinetic (PK)-Evaluable Population

Tmax of INCB059872 in Plasma When Received as Monotherapy

Pharmacokinetic (PK)-Evaluable Population. Only participants with available data were analyzed.

AUC(0-τ) of INCB059872 in Plasma When Received as Monotherapy

t1/2 of INCB059872 in Plasma When Received as Monotherapy

CL/F of INCB059872 in Plasma When Received as Monotherapy

Full Analysis Set. Only participants with SCLC who received combination therapy and had available data were analyzed.

ORR in Participants With SCLC Who Received Combination Therapy

Full Analysis Set. Only participants with AML who received combination therapy were analyzed.

ORR for Altering the Natural History of the Disease in Participants With AML Who Received Combination Therapy

Full Analysis Set. Only participants with MDS who received combination therapy were analyzed.

ORR for Altering the Natural History of the Disease in Participants With MDS Who Received Combination Therapy

Cmax of INCB059872 in Plasma When Received as Combination Therapy

Tmax of INCB059872 in Plasma When Received as Combination Therapy

AUC(0-τ) of INCB059872 in Plasma When Received as Combination Therapy

t1/2 of INCB059872 in Plasma When Received as Combination Therapy

CL/F of INCB059872 in Plasma When Received as Combination Therapy

Monotherapy

Combination Therapy

INCB007839 100 or 200 mg/dose as IR capsules

INCB007839

William V Williams, MD

To establish the maximum tolerated dose (MTD) of INCB007839 given as multiple doses for 28 days and to determine if a higher MTD can be established when INCB007839 is administered in combination with prophylactic anticoagulation and with a 2 and a half day (5 doses) treatment interruption every two weeks.

Open-Label Study to Assess the Safety/Tolerability in Patients With Solid Tumors

A Phase I, Open-Label, Dose-Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of INCB007839 Following Multiple Oral Doses in Patients With Solid Tumors

Carcinoma, Non-Small-Cell Lung

Carcinoma

Recurrence

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Mitogens

Erlotinib Hydrochloride

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

tablets to be administered by mouth once daily at dose selected from safety run-in phase

Itacitinib

150 mg tablets administered by mouth once daily at total daily dose of 150 mg

erlotinib

matching placebo tablets to be administered by mouth at dose selected from safety run-in phase

placebo

Gerard T. Kennealey, M.D.

The purpose of this study is to determine if Itacitinib in combination with erlotinib is safe and effective in the treatment of nonsquamous non-small cell lung cancer (NSCLC) that is Stage IIIB/Stage IV or recurrent whose tumors have EGFR activating mutations.

The study consists of an open-label, safety run-in to confirm the safety of Itacitinibin combination with erlotinib in subjects with nonsquamous non-small cell lung cancer (NSCLC) that is Stage IIIB, Stage IV, or recurrent whose tumors have EGFR activating mutations. Subjects in the safety run-in will receive open-label Itacitinib and erlotinib.

In the second part of the study, subjects will be enrolled and randomized to receive erlotinib (open-label) and either Itacitinib or placebo in a blinded manner. The dose of Itacitinib administered will be determined from the data produced in the safety run-in phase.

Treatment will consist of repeating 21-day cycles. Subjects will take erlotinib tablets daily and Itacitinib/placebo will be self-administered daily during the entire cycle.

Itacitinib in Combination With Erlotinib in Non Small Cell Lung Cancer Patients With Epidermal Growth Factor Receptor (EGFR) Activating Mutations

A Randomized, Double-blind Phase 2 Study of Itacitinib in Combination With Erlotinib Versus Erlotinib Alone in Subjects With Stage IIIB/ IV or Recurrent Non-Small Cell Lung Cancer (NSCLC) Whose Tumors Have Epidermal Growth Factor Receptor (EGFR) Activating Mutations

Subjects will take erlotinib daily and begin dosing with itacitinib once daily (QD) on Cycle 1, Day 1. The safety and tolerability of the regimen will be assessed during the first 21 days of therapy

PFS is defined as the time from randomization until the earliest date of disease progression determined by investigator assessment of objective radiographic disease assessments per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause if sooner.

Objective response determined by radiographic disease assessments per RECIST (v1.1), by investigator assessment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Dose-escalation Study in Subjects With Advanced Malignancies	NCT01195311	Solid Tumors an...	INCB024360	18 Years -	Incyte Corporation
An Open-Label, Dose-Escalation/Dose-Expansion Safety Study of INCB059872 in Subjects With Advanced Malignancies	NCT02712905	Solid Tumors an...	INCB059872 all-trans retin... azacitidine nivolumab	18 Years -	Incyte Corporation
Open-Label Study to Assess the Safety/Tolerability in Patients With Solid Tumors	NCT00820560	Solid Tumors an...	INCB007839	18 Years -	Incyte Corporation
Itacitinib in Combination With Erlotinib in Non Small Cell Lung Cancer Patients With Epidermal Growth Factor Receptor (EGFR) Activating Mutations	NCT02355431	Solid Tumors an... NSCLC (Non-smal...	Itacitinib erlotinib placebo	18 Years -	Incyte Corporation
A Trial to Evaluate Safety and Tolerability of INCSHR01210 in Cancer Patients	NCT02492789	Solid Tumors an...	INCSHR01210 inj...	18 Years -	Atridia Pty Ltd.
A Trial to Evaluate Safety and Tolerability of INCSHR01210 in Cancer Patients	NCT02492789	Solid Tumors an...	INCSHR01210 inj...	18 Years -	Atridia Pty Ltd.

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