Solid Tumors and Hematologic Malignancy
Conditions
Keywords
Acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), small cell lung cancer (SCLC), myelofibrosis (MF), solid tumor, lysine-specific demethylase 1 (LSD1) inhibitor
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.
Interventions
DRUGINCB059872
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.
DRUGazacitidine
DRUGnivolumab
Sponsors
Incyte Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Receiving INCB059872 Monotherapy With Any Treatment-emergent Adverse Event (TEAE) | up to 588 days | 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. |
| Number of Participants Receiving INCB059872 Combination Therapy With Any TEAE | up to 1387 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR for Altering the Natural History of the Disease in Participants With Myelodysplastic Syndrome (MDS) Who Received INCB059872 Monotherapy | up to 61 days | 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 in Spleen Volume Reduction (SVR) at Week 12 in Participants With Myelofibrosis (MF) Who Received INCB059872 Monotherapy | Baseline; Week 12 | 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 of INCB059872 in Plasma When Received as Monotherapy | Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose | Cmax was defined as the maximum observed plasma concentration of INCB059872. |
| Tmax of INCB059872 in Plasma When Received as Monotherapy | Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose | tmax was defined as the time to the maximum observed plasma concentration of INCB059872. |
| AUC(0-τ) of INCB059872 in Plasma When Received as Monotherapy | Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose | 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 of INCB059872 in Plasma When Received as Monotherapy | Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose | t1/2 was defined as the half-life of INCB059872. |
| CL/F of INCB059872 in Plasma When Received as Monotherapy | Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose | CL/F was defined as the apparent oral clearance of INCB059872. |
| Objective Response Rate (ORR) in Participants With the Indicated Type of Solid Tumors Who Received INCB059872 Monotherapy | up to 518 days | 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 for Altering the Natural History of the Disease in Participants With AML Who Received Combination Therapy | up to 208 days | 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 for Altering the Natural History of the Disease in Participants With MDS Who Received Combination Therapy | up to 85 days | 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. |
| Cmax of INCB059872 in Plasma When Received as Combination Therapy | Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose | Cmax was defined as the maximum observed plasma concentration of INCB059872. |
| Tmax of INCB059872 in Plasma When Received as Combination Therapy | Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose | tmax was defined as the time to the maximum observed plasma concentration of INCB059872. |
| AUC(0-τ) of INCB059872 in Plasma When Received as Combination Therapy | Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose | 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 of INCB059872 in Plasma When Received as Combination Therapy | Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose | t1/2 was defined as the half-life of INCB059872. |
| CL/F of INCB059872 in Plasma When Received as Combination Therapy | Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose | CL/F was defined as the apparent oral clearance of INCB059872. |
| ORR in Participants With SCLC Who Received Combination Therapy | up to 1353 days | 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 for Altering the Natural History of the Disease in Participants With Acute Myeloid Leukemia (AML) Who Received INCB059872 Monotherapy | up to 85 days | 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. |
Countries
Belgium, Netherlands, United States
Participant flow
Pre-assignment details
Participants were enrolled at 12 study sites: 10 in the United States and 1 each in Belgium and the Netherlands.
Participants by arm
| Arm | Count |
|---|---|
| Group A: INCB059872 Monotherapy; 2 mg QOD 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. | 3 |
| Group A: INCB059872 Monotherapy; 2 mg QD Participants with AML or MDS received oral INB059872 2 mg as monotherapy once daily (QD) on a 28-day continuous therapy cycle. | 6 |
| Group A: INCB059872 Monotherapy; 3 mg QOD Participants with AML or MDS received oral INB059872 3 mg as monotherapy QOD on a 28-day continuous therapy cycle. | 1 |
| Group A: INCB059872 Monotherapy; 3 mg QD Participants with AML or MDS received oral INB059872 3 mg as monotherapy QD on a 28-day continuous therapy cycle. | 5 |
| Group A: INCB059872 Monotherapy; 4 mg QD Participants with AML or MDS received oral INB059872 4 mg as monotherapy QD on a 28-day continuous therapy cycle. | 18 |
| Group A: INCB059872 Monotherapy; 5 mg QD Participants with AML or MDS received oral INB059872 5 mg as monotherapy QD on a 28-day continuous therapy cycle. | 2 |
| Group B: INCB059872 Monotherapy; 1 mg QD 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. | 3 |
| Group B: INCB059872 Monotherapy; 2 mg QOD 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. | 3 |
| Group B: INCB059872 Monotherapy; 2 mg QD 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. | 1 |
| Group B: INCB059872 Monotherapy; 3 mg QOD 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. | 36 |
| Group B: INCB059872 Monotherapy; 3 mg QD 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. | 3 |
| Group B: INCB059872 Monotherapy; 4 mg QOD 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. | 7 |
| Group C: Combination Therapy; INCB059872 2 mg QD + ATRA 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. | 5 |
| Group C: Combination Therapy; INCB059872 3 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. | 7 |
| Group C: Combination Therapy; INCB059872 4 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. | 1 |
| Group D: Combination Therapy; INCB059872 2 mg QD + Azacitidine 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. | 7 |
| Group D: Combination Therapy; INCB059872 3 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. | 1 |
| Group E: Combination Therapy; INCB059872 3 mg QOD + Nivolumab 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. | 6 |
| Total | 115 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Combination Therapy | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 6 | 1 | 3 | 1 | 3 |
| Combination Therapy | Study Terminated by Sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 0 | 1 |
| Combination Therapy | Unknown; Did Not Complete End of Study Case Report Form Prior to Site Closure | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Combination Therapy | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 2 |
| Monotherapy | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Monotherapy | Death | 2 | 5 | 0 | 3 | 15 | 1 | 3 | 3 | 0 | 27 | 2 | 5 | 0 | 0 | 0 | 0 | 0 | 0 |
| Monotherapy | Lost to Follow-up | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Monotherapy | Physician Decision | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Monotherapy | Started New Cancer Drug | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Monotherapy | Study Terminated by Sponsor | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Monotherapy | Withdrawal by Subject | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 4 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Group A: INCB059872 Monotherapy; 2 mg QOD | Group C: Combination Therapy; INCB059872 4 mg QD + ATRA | Group C: Combination Therapy; INCB059872 3 mg QD + ATRA | Group C: Combination Therapy; INCB059872 2 mg QD + ATRA | Group B: INCB059872 Monotherapy; 4 mg QOD | Group B: INCB059872 Monotherapy; 3 mg QD | Group B: INCB059872 Monotherapy; 3 mg QOD | Group B: INCB059872 Monotherapy; 2 mg QD | Group B: INCB059872 Monotherapy; 2 mg QOD | Group B: INCB059872 Monotherapy; 1 mg QD | Group A: INCB059872 Monotherapy; 5 mg QD | Group A: INCB059872 Monotherapy; 4 mg QD | Group A: INCB059872 Monotherapy; 3 mg QD | Group A: INCB059872 Monotherapy; 3 mg QOD | Group A: INCB059872 Monotherapy; 2 mg QD | Group D: Combination Therapy; INCB059872 2 mg QD + Azacitidine | Group D: Combination Therapy; INCB059872 3 mg QD + Azacitidine | Group E: Combination Therapy; INCB059872 3 mg QOD + Nivolumab | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 65.0 years STANDARD_DEVIATION 5.2 | NA years | 63.6 years STANDARD_DEVIATION 13.83 | 61.0 years STANDARD_DEVIATION 9.19 | 63.0 years STANDARD_DEVIATION 4.86 | 51.0 years STANDARD_DEVIATION 11.53 | 57.8 years STANDARD_DEVIATION 13.95 | NA years | 63.0 years STANDARD_DEVIATION 17.09 | 46.3 years STANDARD_DEVIATION 22.59 | 51.0 years STANDARD_DEVIATION 18.38 | 63.8 years STANDARD_DEVIATION 12.02 | 57.4 years STANDARD_DEVIATION 21.93 | NA years | 58.0 years STANDARD_DEVIATION 9.53 | 73.4 years STANDARD_DEVIATION 9.02 | NA years | 68.7 years STANDARD_DEVIATION 9.48 | 60.8 years STANDARD_DEVIATION 13.39 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | — | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | — | 1 Participants | 0 Participants | — | 0 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | — | 7 Participants | 5 Participants | 7 Participants | 3 Participants | 36 Participants | — | 3 Participants | 3 Participants | 1 Participants | 16 Participants | 5 Participants | — | 5 Participants | 7 Participants | — | 6 Participants | 107 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | — | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | 0 Participants | 0 Participants | — | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American-Indian/Alaska Native | 0 Participants | — | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | — | 0 Participants | 0 Participants | — | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | — | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | — | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | — | 0 Participants | 0 Participants | — | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | — | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants | — | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | — | 2 Participants | 0 Participants | — | 0 Participants | 8 Participants |
| Race/Ethnicity, Customized Declined to Report | 0 Participants | — | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | 0 Participants | 0 Participants | — | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Non-White | 0 Participants | — | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | — | 0 Participants | 0 Participants | — | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Unknown/Not Specified | 0 Participants | — | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | — | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | — | 0 Participants | 0 Participants | — | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 3 Participants | — | 6 Participants | 5 Participants | 6 Participants | 3 Participants | 31 Participants | — | 2 Participants | 2 Participants | 2 Participants | 15 Participants | 4 Participants | — | 4 Participants | 7 Participants | — | 6 Participants | 96 Participants |
| Sex: Female, Male Female | 3 Participants | — | 4 Participants | 0 Participants | 4 Participants | 0 Participants | 16 Participants | — | 3 Participants | 1 Participants | 2 Participants | 9 Participants | 3 Participants | — | 3 Participants | 3 Participants | — | 3 Participants | 54 Participants |
| Sex: Female, Male Male | 0 Participants | — | 3 Participants | 5 Participants | 3 Participants | 3 Participants | 20 Participants | — | 0 Participants | 2 Participants | 0 Participants | 9 Participants | 2 Participants | — | 3 Participants | 4 Participants | — | 3 Participants | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 5 / 6 | 0 / 1 | 4 / 5 | 15 / 18 | 2 / 2 | 3 / 3 | 3 / 3 | 0 / 1 | 27 / 36 | 2 / 3 | 5 / 7 | 5 / 5 | 6 / 7 | 1 / 1 | 3 / 7 | 1 / 1 | 3 / 6 |
| other Total, other adverse events | 3 / 3 | 6 / 6 | 1 / 1 | 5 / 5 | 17 / 18 | 2 / 2 | 3 / 3 | 3 / 3 | 1 / 1 | 35 / 36 | 3 / 3 | 7 / 7 | 4 / 5 | 7 / 7 | 1 / 1 | 7 / 7 | 1 / 1 | 6 / 6 |
| serious Total, serious adverse events | 1 / 3 | 5 / 6 | 0 / 1 | 3 / 5 | 10 / 18 | 2 / 2 | 2 / 3 | 1 / 3 | 1 / 1 | 24 / 36 | 2 / 3 | 3 / 7 | 4 / 5 | 4 / 7 | 0 / 1 | 6 / 7 | 1 / 1 | 2 / 6 |
Outcome results
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.
Time frame: up to 1387 days
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A: INCB059872 Monotherapy; 2 mg QOD | Number of Participants Receiving INCB059872 Combination Therapy With Any TEAE | 5 Participants |
| Group A: INCB059872 Monotherapy; 2 mg QD | Number of Participants Receiving INCB059872 Combination Therapy With Any TEAE | 7 Participants |
| Group A: INCB059872 Monotherapy; 3 mg QOD | Number of Participants Receiving INCB059872 Combination Therapy With Any TEAE | 1 Participants |
| Group A: INCB059872 Monotherapy; 3 mg QD | Number of Participants Receiving INCB059872 Combination Therapy With Any TEAE | 7 Participants |
| Group A: INCB059872 Monotherapy; 4 mg QD | Number of Participants Receiving INCB059872 Combination Therapy With Any TEAE | 1 Participants |
| Group A: INCB059872 Monotherapy; 5 mg QD | Number of Participants Receiving INCB059872 Combination Therapy With Any TEAE | 6 Participants |
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.
Time frame: up to 588 days
Population: Safety Population: all enrolled participants who received at least 1 dose of INCB059872, ATRA, azacitidine, or nivolumab
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A: INCB059872 Monotherapy; 2 mg QOD | Number of Participants Receiving INCB059872 Monotherapy With Any Treatment-emergent Adverse Event (TEAE) | 3 Participants |
| Group A: INCB059872 Monotherapy; 2 mg QD | Number of Participants Receiving INCB059872 Monotherapy With Any Treatment-emergent Adverse Event (TEAE) | 6 Participants |
| Group A: INCB059872 Monotherapy; 3 mg QOD | Number of Participants Receiving INCB059872 Monotherapy With Any Treatment-emergent Adverse Event (TEAE) | 1 Participants |
| Group A: INCB059872 Monotherapy; 3 mg QD | Number of Participants Receiving INCB059872 Monotherapy With Any Treatment-emergent Adverse Event (TEAE) | 5 Participants |
| Group A: INCB059872 Monotherapy; 4 mg QD | Number of Participants Receiving INCB059872 Monotherapy With Any Treatment-emergent Adverse Event (TEAE) | 18 Participants |
| Group A: INCB059872 Monotherapy; 5 mg QD | Number of Participants Receiving INCB059872 Monotherapy With Any Treatment-emergent Adverse Event (TEAE) | 2 Participants |
| Group B: INCB059872 Monotherapy; 1 mg QD | Number of Participants Receiving INCB059872 Monotherapy With Any Treatment-emergent Adverse Event (TEAE) | 3 Participants |
| Group B: INCB059872 Monotherapy; 2 mg QOD | Number of Participants Receiving INCB059872 Monotherapy With Any Treatment-emergent Adverse Event (TEAE) | 3 Participants |
| Group B: INCB059872 Monotherapy; 2 mg QD | Number of Participants Receiving INCB059872 Monotherapy With Any Treatment-emergent Adverse Event (TEAE) | 1 Participants |
| Group B: INCB059872 Monotherapy; 3 mg QOD | Number of Participants Receiving INCB059872 Monotherapy With Any Treatment-emergent Adverse Event (TEAE) | 36 Participants |
| Group B: INCB059872 Monotherapy; 3 mg QD | Number of Participants Receiving INCB059872 Monotherapy With Any Treatment-emergent Adverse Event (TEAE) | 3 Participants |
| Group B: INCB059872 Monotherapy; 4 mg QOD | Number of Participants Receiving INCB059872 Monotherapy With Any Treatment-emergent Adverse Event (TEAE) | 7 Participants |
Secondary
AUC(0-τ) of INCB059872 in Plasma When Received as Combination Therapy
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.
Time frame: Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose
Population: PK-Evaluable Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: INCB059872 Monotherapy; 2 mg QOD | AUC(0-τ) of INCB059872 in Plasma When Received as Combination Therapy | 225 nM x hour | Standard Deviation 85.9 |
| Group A: INCB059872 Monotherapy; 2 mg QD | AUC(0-τ) of INCB059872 in Plasma When Received as Combination Therapy | 377 nM x hour | Standard Deviation 25.7 |
| Group A: INCB059872 Monotherapy; 3 mg QD | AUC(0-τ) of INCB059872 in Plasma When Received as Combination Therapy | 273 nM x hour | Standard Deviation 24.4 |
| Group A: INCB059872 Monotherapy; 5 mg QD | AUC(0-τ) of INCB059872 in Plasma When Received as Combination Therapy | 357 nM x hour | Standard Deviation 97.5 |
Secondary
AUC(0-τ) of INCB059872 in Plasma When Received as Monotherapy
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.
Time frame: Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose
Population: Pharmacokinetic (PK)-Evaluable Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: INCB059872 Monotherapy; 2 mg QOD | AUC(0-τ) of INCB059872 in Plasma When Received as Monotherapy | 196 nM x hour | Standard Deviation 8.38 |
| Group A: INCB059872 Monotherapy; 2 mg QD | AUC(0-τ) of INCB059872 in Plasma When Received as Monotherapy | 216 nM x hour | Standard Deviation 75.5 |
| Group A: INCB059872 Monotherapy; 3 mg QD | AUC(0-τ) of INCB059872 in Plasma When Received as Monotherapy | 374 nM x hour | Standard Deviation 120 |
| Group A: INCB059872 Monotherapy; 4 mg QD | AUC(0-τ) of INCB059872 in Plasma When Received as Monotherapy | 486 nM x hour | Standard Deviation 107 |
| Group A: INCB059872 Monotherapy; 5 mg QD | AUC(0-τ) of INCB059872 in Plasma When Received as Monotherapy | NA nM x hour | — |
| Group B: INCB059872 Monotherapy; 1 mg QD | AUC(0-τ) of INCB059872 in Plasma When Received as Monotherapy | NA nM x hour | — |
| Group B: INCB059872 Monotherapy; 2 mg QOD | AUC(0-τ) of INCB059872 in Plasma When Received as Monotherapy | NA nM x hour | — |
| Group B: INCB059872 Monotherapy; 3 mg QOD | AUC(0-τ) of INCB059872 in Plasma When Received as Monotherapy | 361 nM x hour | Standard Deviation 115 |
| Group B: INCB059872 Monotherapy; 3 mg QD | AUC(0-τ) of INCB059872 in Plasma When Received as Monotherapy | NA nM x hour | — |
| Group B: INCB059872 Monotherapy; 4 mg QOD | AUC(0-τ) of INCB059872 in Plasma When Received as Monotherapy | 495 nM x hour | Standard Deviation 63.2 |
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.
Time frame: Baseline; Week 12
Population: Full Analysis Set. Analysis was not conducted because no participants with MF remained in the study at Week 12.
Secondary
CL/F of INCB059872 in Plasma When Received as Combination Therapy
CL/F was defined as the apparent oral clearance of INCB059872.
Time frame: Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose
Population: PK-Evaluable Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: INCB059872 Monotherapy; 2 mg QOD | CL/F of INCB059872 in Plasma When Received as Combination Therapy | 25.1 Liters per hour | Standard Deviation 7.21 |
| Group A: INCB059872 Monotherapy; 2 mg QD | CL/F of INCB059872 in Plasma When Received as Combination Therapy | 20.7 Liters per hour | Standard Deviation 1.41 |
| Group A: INCB059872 Monotherapy; 3 mg QD | CL/F of INCB059872 in Plasma When Received as Combination Therapy | 19.0 Liters per hour | Standard Deviation 1.7 |
| Group A: INCB059872 Monotherapy; 5 mg QD | CL/F of INCB059872 in Plasma When Received as Combination Therapy | 23.5 Liters per hour | Standard Deviation 8.14 |
Secondary
CL/F of INCB059872 in Plasma When Received as Monotherapy
CL/F was defined as the apparent oral clearance of INCB059872.
Time frame: Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose
Population: Pharmacokinetic (PK)-Evaluable Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: INCB059872 Monotherapy; 2 mg QOD | CL/F of INCB059872 in Plasma When Received as Monotherapy | 32.9 Liters per hour | Standard Deviation 7.94 |
| Group A: INCB059872 Monotherapy; 2 mg QD | CL/F of INCB059872 in Plasma When Received as Monotherapy | 26.3 Liters per hour | Standard Deviation 9.31 |
| Group A: INCB059872 Monotherapy; 3 mg QD | CL/F of INCB059872 in Plasma When Received as Monotherapy | 22.1 Liters per hour | Standard Deviation 6.56 |
| Group A: INCB059872 Monotherapy; 4 mg QD | CL/F of INCB059872 in Plasma When Received as Monotherapy | 22.1 Liters per hour | Standard Deviation 5.57 |
| Group A: INCB059872 Monotherapy; 5 mg QD | CL/F of INCB059872 in Plasma When Received as Monotherapy | NA Liters per hour | — |
| Group B: INCB059872 Monotherapy; 1 mg QD | CL/F of INCB059872 in Plasma When Received as Monotherapy | NA Liters per hour | — |
| Group B: INCB059872 Monotherapy; 2 mg QOD | CL/F of INCB059872 in Plasma When Received as Monotherapy | NA Liters per hour | — |
| Group B: INCB059872 Monotherapy; 3 mg QOD | CL/F of INCB059872 in Plasma When Received as Monotherapy | 23.1 Liters per hour | Standard Deviation 6.32 |
| Group B: INCB059872 Monotherapy; 3 mg QD | CL/F of INCB059872 in Plasma When Received as Monotherapy | NA Liters per hour | — |
| Group B: INCB059872 Monotherapy; 4 mg QOD | CL/F of INCB059872 in Plasma When Received as Monotherapy | 21.1 Liters per hour | Standard Deviation 2.74 |
Secondary
Cmax of INCB059872 in Plasma When Received as Combination Therapy
Cmax was defined as the maximum observed plasma concentration of INCB059872.
Time frame: Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose
Population: PK-Evaluable Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: INCB059872 Monotherapy; 2 mg QOD | Cmax of INCB059872 in Plasma When Received as Combination Therapy | 44.3 nM | Standard Deviation 16.4 |
| Group A: INCB059872 Monotherapy; 2 mg QD | Cmax of INCB059872 in Plasma When Received as Combination Therapy | 96.4 nM | Standard Deviation 10.7 |
| Group A: INCB059872 Monotherapy; 3 mg QD | Cmax of INCB059872 in Plasma When Received as Combination Therapy | 38.2 nM | Standard Deviation 33.5 |
| Group A: INCB059872 Monotherapy; 5 mg QD | Cmax of INCB059872 in Plasma When Received as Combination Therapy | 78.0 nM | Standard Deviation 26.3 |
Secondary
Cmax of INCB059872 in Plasma When Received as Monotherapy
Cmax was defined as the maximum observed plasma concentration of INCB059872.
Time frame: Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose
Population: Pharmacokinetic (PK)-Evaluable Population: all participants who received at least 1 dose of study treatment and provided at least 1 postdose PK sample
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: INCB059872 Monotherapy; 2 mg QOD | Cmax of INCB059872 in Plasma When Received as Monotherapy | 33.4 nanomolar (nM) | Standard Deviation 29.2 |
| Group A: INCB059872 Monotherapy; 2 mg QD | Cmax of INCB059872 in Plasma When Received as Monotherapy | 46.0 nanomolar (nM) | Standard Deviation 12.5 |
| Group A: INCB059872 Monotherapy; 3 mg QD | Cmax of INCB059872 in Plasma When Received as Monotherapy | 73.1 nanomolar (nM) | Standard Deviation 30.5 |
| Group A: INCB059872 Monotherapy; 4 mg QD | Cmax of INCB059872 in Plasma When Received as Monotherapy | 110 nanomolar (nM) | Standard Deviation 13.7 |
| Group A: INCB059872 Monotherapy; 5 mg QD | Cmax of INCB059872 in Plasma When Received as Monotherapy | NA nanomolar (nM) | — |
| Group B: INCB059872 Monotherapy; 1 mg QD | Cmax of INCB059872 in Plasma When Received as Monotherapy | 25.7 nanomolar (nM) | Standard Deviation 21.8 |
| Group B: INCB059872 Monotherapy; 2 mg QOD | Cmax of INCB059872 in Plasma When Received as Monotherapy | 46.0 nanomolar (nM) | Standard Deviation 9.95 |
| Group B: INCB059872 Monotherapy; 3 mg QOD | Cmax of INCB059872 in Plasma When Received as Monotherapy | 70.6 nanomolar (nM) | Standard Deviation 25.6 |
| Group B: INCB059872 Monotherapy; 3 mg QD | Cmax of INCB059872 in Plasma When Received as Monotherapy | NA nanomolar (nM) | — |
| Group B: INCB059872 Monotherapy; 4 mg QOD | Cmax of INCB059872 in Plasma When Received as Monotherapy | 98.2 nanomolar (nM) | Standard Deviation 28.5 |
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.
Time frame: up to 518 days
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group B: INCB059872 Monotherapy; 1 mg QD | Objective Response Rate (ORR) in Participants With the Indicated Type of Solid Tumors Who Received INCB059872 Monotherapy | Poorly differentiated neuroendocrine tumors | 0.0 percentage of participants |
| Group B: INCB059872 Monotherapy; 1 mg QD | Objective Response Rate (ORR) in Participants With the Indicated Type of Solid Tumors Who Received INCB059872 Monotherapy | Other solid tumors | 0.0 percentage of participants |
| Group B: INCB059872 Monotherapy; 2 mg QOD | Objective Response Rate (ORR) in Participants With the Indicated Type of Solid Tumors Who Received INCB059872 Monotherapy | Other solid tumors | 0.0 percentage of participants |
| Group B: INCB059872 Monotherapy; 2 mg QD | Objective Response Rate (ORR) in Participants With the Indicated Type of Solid Tumors Who Received INCB059872 Monotherapy | Other solid tumors | 0.0 percentage of participants |
| Group B: INCB059872 Monotherapy; 3 mg QOD | Objective Response Rate (ORR) in Participants With the Indicated Type of Solid Tumors Who Received INCB059872 Monotherapy | SCLC | 0.0 percentage of participants |
| Group B: INCB059872 Monotherapy; 3 mg QOD | Objective Response Rate (ORR) in Participants With the Indicated Type of Solid Tumors Who Received INCB059872 Monotherapy | Ewing's sarcoma | 0.0 percentage of participants |
| Group B: INCB059872 Monotherapy; 3 mg QOD | Objective Response Rate (ORR) in Participants With the Indicated Type of Solid Tumors Who Received INCB059872 Monotherapy | Poorly differentiated neuroendocrine tumors | 0.0 percentage of participants |
| Group B: INCB059872 Monotherapy; 3 mg QOD | Objective Response Rate (ORR) in Participants With the Indicated Type of Solid Tumors Who Received INCB059872 Monotherapy | Other solid tumors | 0.0 percentage of participants |
| Group B: INCB059872 Monotherapy; 3 mg QD | Objective Response Rate (ORR) in Participants With the Indicated Type of Solid Tumors Who Received INCB059872 Monotherapy | SCLC | 0.0 percentage of participants |
| Group B: INCB059872 Monotherapy; 3 mg QD | Objective Response Rate (ORR) in Participants With the Indicated Type of Solid Tumors Who Received INCB059872 Monotherapy | Other solid tumors | 50.0 percentage of participants |
| Group B: INCB059872 Monotherapy; 4 mg QOD | Objective Response Rate (ORR) in Participants With the Indicated Type of Solid Tumors Who Received INCB059872 Monotherapy | Other solid tumors | 0.0 percentage of participants |
| Group B: INCB059872 Monotherapy; 4 mg QOD | Objective Response Rate (ORR) in Participants With the Indicated Type of Solid Tumors Who Received INCB059872 Monotherapy | SCLC | 0.0 percentage of participants |
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.
Time frame: up to 85 days
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A: INCB059872 Monotherapy; 2 mg QOD | ORR for Altering the Natural History of the Disease in Participants With Acute Myeloid Leukemia (AML) Who Received INCB059872 Monotherapy | 0.0 percentage of participants |
| Group A: INCB059872 Monotherapy; 2 mg QD | ORR for Altering the Natural History of the Disease in Participants With Acute Myeloid Leukemia (AML) Who Received INCB059872 Monotherapy | 0.0 percentage of participants |
| Group A: INCB059872 Monotherapy; 3 mg QD | ORR for Altering the Natural History of the Disease in Participants With Acute Myeloid Leukemia (AML) Who Received INCB059872 Monotherapy | 0.0 percentage of participants |
| Group A: INCB059872 Monotherapy; 4 mg QD | ORR for Altering the Natural History of the Disease in Participants With Acute Myeloid Leukemia (AML) Who Received INCB059872 Monotherapy | 0.0 percentage of participants |
| Group A: INCB059872 Monotherapy; 5 mg QD | ORR for Altering the Natural History of the Disease in Participants With Acute Myeloid Leukemia (AML) Who Received INCB059872 Monotherapy | 0.0 percentage of participants |
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.
Time frame: up to 208 days
Population: Full Analysis Set. Only participants with AML who received combination therapy were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A: INCB059872 Monotherapy; 2 mg QOD | ORR for Altering the Natural History of the Disease in Participants With AML Who Received Combination Therapy | 20.0 percentage of participants |
| Group A: INCB059872 Monotherapy; 2 mg QD | ORR for Altering the Natural History of the Disease in Participants With AML Who Received Combination Therapy | 0.0 percentage of participants |
| Group A: INCB059872 Monotherapy; 3 mg QOD | ORR for Altering the Natural History of the Disease in Participants With AML Who Received Combination Therapy | 0.0 percentage of participants |
| Group A: INCB059872 Monotherapy; 3 mg QD | ORR for Altering the Natural History of the Disease in Participants With AML Who Received Combination Therapy | 16.7 percentage of participants |
| Group A: INCB059872 Monotherapy; 4 mg QD | ORR for Altering the Natural History of the Disease in Participants With AML Who Received Combination Therapy | 0.0 percentage of participants |
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.
Time frame: up to 85 days
Population: Full Analysis Set. Only participants with MDS who received combination therapy were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A: INCB059872 Monotherapy; 3 mg QD | ORR for Altering the Natural History of the Disease in Participants With MDS Who Received Combination Therapy | 0.0 percentage of participants |
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.
Time frame: up to 61 days
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A: INCB059872 Monotherapy; 2 mg QD | ORR for Altering the Natural History of the Disease in Participants With Myelodysplastic Syndrome (MDS) Who Received INCB059872 Monotherapy | 0.0 percentage of participants |
| Group A: INCB059872 Monotherapy; 3 mg QD | ORR for Altering the Natural History of the Disease in Participants With Myelodysplastic Syndrome (MDS) Who Received INCB059872 Monotherapy | 0.0 percentage of participants |
| Group A: INCB059872 Monotherapy; 4 mg QD | ORR for Altering the Natural History of the Disease in Participants With Myelodysplastic Syndrome (MDS) Who Received INCB059872 Monotherapy | 0.0 percentage of participants |
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.
Time frame: up to 1353 days
Population: Full Analysis Set. Only participants with SCLC who received combination therapy and had available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A: INCB059872 Monotherapy; 5 mg QD | ORR in Participants With SCLC Who Received Combination Therapy | 20.0 percentage of participants |
Secondary
t1/2 of INCB059872 in Plasma When Received as Combination Therapy
t1/2 was defined as the half-life of INCB059872.
Time frame: Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose
Population: PK-Evaluable Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: INCB059872 Monotherapy; 2 mg QOD | t1/2 of INCB059872 in Plasma When Received as Combination Therapy | 3.95 hours | Standard Deviation 0.499 |
| Group A: INCB059872 Monotherapy; 2 mg QD | t1/2 of INCB059872 in Plasma When Received as Combination Therapy | 3.41 hours | Standard Deviation 0.281 |
| Group A: INCB059872 Monotherapy; 3 mg QD | t1/2 of INCB059872 in Plasma When Received as Combination Therapy | 3.08 hours | Standard Deviation 0.04 |
| Group A: INCB059872 Monotherapy; 5 mg QD | t1/2 of INCB059872 in Plasma When Received as Combination Therapy | 3.79 hours | Standard Deviation 0.852 |
Secondary
t1/2 of INCB059872 in Plasma When Received as Monotherapy
t1/2 was defined as the half-life of INCB059872.
Time frame: Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose
Population: Pharmacokinetic (PK)-Evaluable Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: INCB059872 Monotherapy; 2 mg QOD | t1/2 of INCB059872 in Plasma When Received as Monotherapy | 3.15 hours | Standard Deviation 0.189 |
| Group A: INCB059872 Monotherapy; 2 mg QD | t1/2 of INCB059872 in Plasma When Received as Monotherapy | 3.30 hours | Standard Deviation 0.765 |
| Group A: INCB059872 Monotherapy; 3 mg QD | t1/2 of INCB059872 in Plasma When Received as Monotherapy | 3.13 hours | Standard Deviation 0.495 |
| Group A: INCB059872 Monotherapy; 4 mg QD | t1/2 of INCB059872 in Plasma When Received as Monotherapy | 3.67 hours | Standard Deviation 1.38 |
| Group A: INCB059872 Monotherapy; 5 mg QD | t1/2 of INCB059872 in Plasma When Received as Monotherapy | NA hours | — |
| Group B: INCB059872 Monotherapy; 1 mg QD | t1/2 of INCB059872 in Plasma When Received as Monotherapy | NA hours | — |
| Group B: INCB059872 Monotherapy; 2 mg QOD | t1/2 of INCB059872 in Plasma When Received as Monotherapy | NA hours | — |
| Group B: INCB059872 Monotherapy; 3 mg QOD | t1/2 of INCB059872 in Plasma When Received as Monotherapy | 3.57 hours | Standard Deviation 0.52 |
| Group B: INCB059872 Monotherapy; 3 mg QD | t1/2 of INCB059872 in Plasma When Received as Monotherapy | NA hours | — |
| Group B: INCB059872 Monotherapy; 4 mg QOD | t1/2 of INCB059872 in Plasma When Received as Monotherapy | 4.28 hours | Standard Deviation 0.25 |
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.
Time frame: Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose
Population: PK-Evaluable Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A: INCB059872 Monotherapy; 2 mg QOD | Tmax of INCB059872 in Plasma When Received as Combination Therapy | 1.0 hours |
| Group A: INCB059872 Monotherapy; 2 mg QD | Tmax of INCB059872 in Plasma When Received as Combination Therapy | 0.5 hours |
| Group A: INCB059872 Monotherapy; 3 mg QD | Tmax of INCB059872 in Plasma When Received as Combination Therapy | 0.5 hours |
| Group A: INCB059872 Monotherapy; 5 mg QD | Tmax of INCB059872 in Plasma When Received as Combination Therapy | 1.0 hours |
Secondary
Tmax of INCB059872 in Plasma When Received as Monotherapy
tmax was defined as the time to the maximum observed plasma concentration of INCB059872.
Time frame: Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose
Population: Pharmacokinetic (PK)-Evaluable Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A: INCB059872 Monotherapy; 2 mg QOD | Tmax of INCB059872 in Plasma When Received as Monotherapy | 0.5 hours |
| Group A: INCB059872 Monotherapy; 2 mg QD | Tmax of INCB059872 in Plasma When Received as Monotherapy | 1 hours |
| Group A: INCB059872 Monotherapy; 3 mg QD | Tmax of INCB059872 in Plasma When Received as Monotherapy | 1 hours |
| Group A: INCB059872 Monotherapy; 4 mg QD | Tmax of INCB059872 in Plasma When Received as Monotherapy | 0.5 hours |
| Group A: INCB059872 Monotherapy; 5 mg QD | Tmax of INCB059872 in Plasma When Received as Monotherapy | NA hours |
| Group B: INCB059872 Monotherapy; 1 mg QD | Tmax of INCB059872 in Plasma When Received as Monotherapy | 2.0 hours |
| Group B: INCB059872 Monotherapy; 2 mg QOD | Tmax of INCB059872 in Plasma When Received as Monotherapy | 2 hours |
| Group B: INCB059872 Monotherapy; 3 mg QOD | Tmax of INCB059872 in Plasma When Received as Monotherapy | 1 hours |
| Group B: INCB059872 Monotherapy; 3 mg QD | Tmax of INCB059872 in Plasma When Received as Monotherapy | NA hours |
| Group B: INCB059872 Monotherapy; 4 mg QOD | Tmax of INCB059872 in Plasma When Received as Monotherapy | 0.5 hours |