Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
Phase 2: Progression Free Survival (PFS), as Determined by the Local Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) |
PFS was defined as the number of months from randomization to progressive disease (PD) or death due to any cause, whichever occurred first. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm); the appearance of one or more new lesions; and unequivocal progression of existing non-target lesions. |
From date of randomization to PD or death due to any cause (maximum exposure: 24 cycles [each cycle = 14 days]) |
|
| Primary |
Phase 1b: Number of Participants With at Least One Dose Limiting Toxicity (DLT) Adverse Event (AE) |
A DLT was defined as the occurrence of any protocol-specified event within the first 2 cycles of treatment (from Cycle 1 Day 1 through the end of Cycle 2) of entinostat in combination with avelumab that were considered by the investigator to be at least possibly related to study drug. |
Day 1 through Day 28 (Cycles 1 and 2) |
|
| Secondary |
Phase 1b: Recommended Phase 2 Dose (RP2D) |
The RP2D was determined in discussion with the Sponsor, Medical Monitor, and Dose Determination Phase Investigators. Additionally, observations related to immune correlates, and any cumulative toxicity observed after multiple cycles might be included in the rationale supporting the RP2D. The RP2D could be equal to or less than the preliminary maximum tolerated dose (MTD). The MTD was defined as the highest dose level at which <33% of 6 participants experienced DLT. |
Day 1 through Day 28 (Cycles 1 and 2) |
|
| Secondary |
Phase 2: PFS, as Determined by the Local Investigator Using Immune Response RECIST (irRECIST) |
PFS was defined as the number of months from randomization to PD or death due to any cause, whichever occurred first. PD: Sum of the diameters (longest for non-nodal lesions, shortest for nodal lesions) of target and new measurable lesions increases =20% (compared to nadir), confirmed by a repeat, consecutive observation at least 4 weeks from the date first documented. |
From date of randomization to PD or death due to any cause (maximum exposure: 24 cycles [each cycle = 14 days]) |
|
| Secondary |
Phase 2: Objective Response Rate (ORR), as Assessed Using RECIST 1.1 |
The ORR was defined as the percentage of participants with confirmed complete response (CR) or partial response (PR). CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalisation of tumour marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
From date of randomization to date of progression (maximum exposure: 24 cycles [each cycle = 14 days]) |
|
| Secondary |
Phase 2: ORR, as Assessed Using irRECIST |
The ORR was defined as the percentage of participants with confirmed CR or PR. CR: Complete disappearance of all lesions (whether measurable or not) and no new lesions. All measurable lymph nodes also must have a reduction in short axis to <10 mm. PR: Sum of the diameters (longest for non-nodal lesions, shortest for nodal lesions) of target and new measurable lesions decreases =30%. |
From date of randomization to date of progression (maximum exposure: 24 cycles [each cycle = 14 days]) |
|
| Secondary |
Phase 2: Clinical Benefit Rate (CBR), as Assessed Using RECIST 1.1 |
The CBR was defined as the percentage of participants with a confirmed CR, PR, or stable disease (SD) lasting for at least 6 months. CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalisation of tumour marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. |
From date of randomization to date of progression (maximum exposure: 24 cycles [each cycle = 14 days]) |
|
| Secondary |
Phase 2: CBR, as Assessed Using irRECIST |
The CBR was defined as the percentage of participants with a confirmed CR, PR, or SD lasting for at least 6 months. CR: Complete disappearance of all lesions (whether measurable or not) and no new lesions. All measurable lymph nodes also must have a reduction in short axis to <10 mm. PR: Sum of the diameters (longest for non-nodal lesions, shortest for nodal lesions) of target and new measurable lesions decreases =30%. SD: Sum of the diameters (longest for nonnodal lesions, shortest for nodal lesions) of target and new measurable lesions neither CR, PR, (compared to baseline) or PD (compared to nadir). |
From date of randomization to date of progression (maximum exposure: 24 cycle [each cycle = 14 days]) |
|
| Secondary |
Phase 2: Overall Survival |
Overall survival was defined as the number of months from randomization to the date of death (due to any cause). |
From date of randomization to the date of death (maximum exposure: 24 cycles [each cycle = 14 days]) |
|
| Secondary |
Phase 2: Duration of Response |
Duration of response was defined as the number of months from the start date of PR or CR (whichever response occurred first) and subsequently confirmed, to the first date that recurrent or progressive disease was documented. CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalisation of tumour marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study .In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm; the appearance of one or more new lesions; and unequivocal progression of existing non-target lesions. |
From start date of CR or PR to date of progression (maximum exposure: 24 cycles [each cycle = 14 days]) |
|
| Secondary |
Phase 2: Time to Response |
Time to response was defined as the number of months from the randomization date to the first date the participant achieved a PR or CR (whichever response occurred first and was subsequently confirmed). CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalisation of tumour marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
From the date of randomization to date of PR or CR (maximum exposure: 24 cycles [each cycle = 14 days]) |
|
| Secondary |
Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), AEs Resulting in the Permanent Discontinuation of Study Drug, and Death |
An adverse event (AE) was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. SAEs included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs were defined as AEs that started on or after the first administration of study drug and within 30 days of the last administration of any study treatment. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'. |
From first dose of study drug up to 30 days after end of treatment (maximum exposure: 24 cycles [each cycle = 14 days]) |
|
| Secondary |
Phase 2: Number of Participants With TEAEs, SAEs, AEs Resulting in the Permanent Discontinuation of Study Drug, and Death |
An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. SAEs included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs were defined as AEs that started on or after the first administration of study drug and within 30 days of the last administration of any study treatment. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'. |
From first dose of study drug up to 30 days after end of treatment (maximum exposure: 24 cycles [each cycle = 14 days]) |
|
| Secondary |
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Avelumab When Given in Combination With Entinostat |
|
Pre-dose and post-infusion on Day 1 of Cycle 1 the 30-day follow-up (maximum exposure: 24 cycles [each cycle = 14 days]) |
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