Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
Phase 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) |
An adverse event (AE) was 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). A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug and until 30 days after the last dose of study drug. |
up to 285 days |
|
| Primary |
Phase 1: Number of Participants With Any Grade 3 or Higher TEAE |
An adverse event (AE) was 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). A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug and until 30 days after the last dose of study drug. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: life-threatening consequences; urgent intervention indicated. |
up to 285 days |
|
| Primary |
Phase 1: Number of Participants With Any Dose-limiting Toxicity (DLT) |
A DLT was defined as the occurrence of any protocol-defined toxicities occurring up to and including Study Day 28, except those with a clear alternative explanation (e.g., disease progression) or transient (=72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination. All DLTs were assessed by the investigator using Common Terminology Criteria for Adverse Events (CTCAE) v4.03 criteria. In order to be included in the tolerability review, subjects must have received the cohort-specific dose of INCB039110 and ibrutinib for at least 75% of the days during the 28-day surveillance period or have experienced a DLT. |
up to Day 28 |
|
| Primary |
Phase 2: Objective Response Rate (ORR), Defined as the Percentage of Participants Achieving Either a Complete Response (CR) or a Partial Response (PR), Per the Modified Lugano Classification for Diffuse Large B-cell Lymphoma (DLBCL) |
CR: (1) target nodes/nodal masses of lymph nodes/extralymphatic sites regressed to =1.5 centimeters (cm) in the longest dimension transverse diameter of lesion (LDi); (2) absence of non-measured lesions; (3) organ enlargement regressed to normal; (4) no new lesions; (5) normal bone marrow morphology; if indeterminate, immunohistochemistry negative. PR: (1) lymph nodes/extralymphatic sites: =50% decrease in the sum of the product of perpendicular diameters for multiple lesions of up to 6 target measurable nodes/extranodal sites; if lesion is too small to measure on computed tomography, assign 5 millimeters (mm) × 5 mm as default; if no longer visible, 0 mm × 0 mm. For node >5 mm × 5 mm but smaller than normal, use actual measurement; (2) absent/regressed non-measured lesions, no increase; (3) organ enlargement; spleen regressed by >50% in length beyond normal; (4) no new lesions. |
up to 1538 days |
|
| Secondary |
Phase 1: ORR, Defined as the Percentage of Participants Achieving Either a CR or a PR, Per the Modified Lugano Classification for DLBCL |
CR: (1) target nodes/nodal masses of lymph nodes/extralymphatic sites regressed to =1.5 cm in the LDi; (2) absence of non-measured lesions; (3) organ enlargement regressed to normal; (4) no new lesions; (5) normal bone marrow morphology; if indeterminate, immunohistochemistry negative. PR: (1) lymph nodes/extralymphatic sites: =50% decrease in the sum of the product of perpendicular diameters for multiple lesions of up to 6 target measurable nodes/extranodal sites; if lesion is too small to measure on computed tomography, assign 5 mm × 5 mm as default; if no longer visible, 0 mm × 0 mm. For node >5 mm × 5 mm but smaller than normal, use actual measurement; (2) absent/regressed non-measured lesions, no increase; (3) organ enlargement; spleen regressed by >50% in length beyond normal; (4) no new lesions. |
up to 250 days |
|
| Secondary |
Phase 2: Duration of Response (DOR): Time From the First Overall Response Contributing to an Objective Response (CR or PR) to the Earlier of the Participant's Death and the First Overall Response of Progressive Disease, Per the Lugano Classification |
Disease progression requires =1 of the following: (1) an abnormal individual node/lesion with all of the following: (a) LDi > 1.5 cm; (b) increase by =50% from cross product of the LDi and the perpendicular diameter (PPD) nadir; (c) increase in LDi or the shortest axis perpendicular to the LDi (SDi) from nadir: (i) 0.5 cm for lesions =2 cm; (ii) 1.0 cm for lesions > 2 cm. (2) For splenomegaly, the splenic length must increased by 50% of the extent of its prior increase beyond baseline. If no prior splenomegaly, must increase by at least 2 cm from baseline. (3) New/recurrent splenomegaly. (4) New/clear progression of preexisting nonmeasured lesions. (5) Regrowth of previously resolved lesions. (6) A new node > 1.5 cm in any axis. (7) A new extranodal site > 1.0 cm in any axis; if < 1.0 cm in any axis, its presence must be unequivocal/attributable to lymphoma. (8) Assessable disease of any size unequivocally attributable to lymphoma. (9) New or recurrent involvement of the bone marrow. |
up to 947 days |
|
| Secondary |
Phase 2: Durable Response Rate (DRR) |
DRR=percentage of participants with a CR or PR, per Lugano Classification, for =16 weeks since the time from the first overall response contributing to an objective response (CR or PR). CR: (1) target nodes/nodal masses of lymph nodes/extralymphatic sites regressed to =1.5 cm in the LDi; (2) absence of non-measured lesions; (3) organ enlargement regressed to normal; (4) no new lesions; (5) normal bone marrow morphology; if indeterminate, immunohistochemistry negative. PR: (1) lymph nodes/extralymphatic sites: =50% decrease in the sum of the product of perpendicular diameters for multiple lesions of up to 6 target measurable nodes/extranodal sites; if lesion is too small to measure on computed tomography, assign 5 mm × 5 mm as default; if no longer visible, 0 mm × 0 mm. For node >5 mm × 5 mm but smaller than normal, use actual measurement; (2) absent/regressed non-measured lesions, no increase; (3) organ enlargement; spleen regressed by >50% in length beyond normal; (4) no new lesions. |
up to 1538 days |
|
| Secondary |
Phase 2: Progression-free Survival (PFS), Defined as the Time From the First Dose to the Earlier Date of Death Due to Any Cause or Disease Progression Determined by Objective Radiographic Disease Assessments |
Disease progression requires =1 of the following: (1) an abnormal individual node/lesion with all of the following: (a) LDi > 1.5 cm; (b) increase by =50% from cross product of the LDi and the perpendicular diameter (PPD) nadir; (c) increase in LDi or the shortest axis perpendicular to the LDi (SDi) from nadir: (i) 0.5 cm for lesions =2 cm; (ii) 1.0 cm for lesions > 2 cm. (2) For splenomegaly, the splenic length must increased by 50% of the extent of its prior increase beyond baseline. If no prior splenomegaly, must increase by at least 2 cm from baseline. (3) New/recurrent splenomegaly. (4) New/clear progression of preexisting nonmeasured lesions. (5) Regrowth of previously resolved lesions. (6) A new node > 1.5 cm in any axis. (7) A new extranodal site > 1.0 cm in any axis; if < 1.0 cm in any axis, its presence must be unequivocal/attributable to lymphoma. (8) Assessable disease of any size unequivocally attributable to lymphoma. (9) New or recurrent involvement of the bone marrow. |
up to 1538 days |
|
| Secondary |
Phase 2: Number of Participants With Any TEAE |
An AE was 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). A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug and until 30 days after the last dose of study drug. |
up to 1573 days |
|
| Secondary |
Phase 2: Number of Participants With Any Grade 3 or Higher TEAE |
An AE was 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). A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug and until 30 days after the last dose of study drug. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: life-threatening consequences; urgent intervention indicated. |
up to 1573 days |
|
