Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
Percentage of Participants With Confirmed Objective Response- Objective Response Rate (ORR) |
ORR: percentage of participants with a confirmed Complete Response (CR) or Partial Response (PR) based on investigator's assessment as per Response Evaluation Criteria in Solid Tumours (RECIST version [v] 1.1). Both CR and PR were confirmed by repeat assessments performed no less than 4 weeks after criteria for response was first met. Per RECIST v1.1: CR was defined as complete disappearance of all target lesions and non-target disease, with exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than [<]10 millimeter [mm]). No new lesions. PR was defined as greater than or equal to (>=) 30 percent (%) decrease under baseline of sum of diameters of all target lesions. Short axis was used in sum for target nodes, while longest diameter was used in sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. Stable disease was defined as not qualifying for CR, PR, Progressive Disease. |
Baseline up to 56 months |
|
| Secondary |
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) During the On-Treatment Period |
An Adverse Event (AE) was any untoward medical occurrence attributed to study drug in a participant who received avelumab or axitinib. Treatment-emergent adverse events (TEAEs) were those events with onset dates occurring during the on-treatment period (the time from the first dose of study treatment through minimum 30 days post last dose of study treatment or start day of new anti-cancer treatment -1 day). |
From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment or start of new anti-cancer treatment -1 day (maximum up to 56 months) |
|
| Secondary |
Percentage of Participants With Hematology Test Results of Maximum National Cancer Institute; Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade During the On-Treatment Period |
The following hematology parameters were assessed: anemia, hemoglobin increased, international normalized ratio (INR) increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased and white blood cell decreased. Laboratory abnormality events were graded according to NCI CTCAE v 4.03 (grade 3= severe and grade 4= life-threatening). Categories with non-zero values are presented. |
From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment or start of new anti-cancer treatment -1 day (maximum up to 56 months) |
|
| Secondary |
Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period |
The following chemistry parameters were assessed: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, cholesterol high, creatine phosphokinase (CPK) increased, creatinine increased, gamma-glutamyl transferase (GGT) increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypertriglyceridemia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, lipase increased and serum amylase increased. Laboratory abnormalities were graded according CTCAE version 4.03 (grade 3= severe, grade 4= life-threatening and grade 5= death related). Categories with non-zero values are presented. |
From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment or start of new anti-cancer treatment -1 day (maximum up to 56 months) |
|
| Secondary |
Time to Tumor Response (TTR) in Participants With Confirmed CR or PR |
TTR was defined as the time from the first dose of study treatment to the first documentation of objective tumor response documented in participants with confirmed objective response (CR or PR). CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. Analysis was performed using Kaplan-Meier method. |
From date of start of treatment until date of first documentation of objective tumor response (maximum up to 56 months) |
|
| Secondary |
Duration of Response in Participants With Confirmed CR or PR |
Duration of response was defined as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first in participants with confirmed objective response (CR or PR). CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. Analysis was performed using Kaplan-Meier method. |
From date of first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first (maximum up to 56 months) |
|
| Secondary |
Progression Free Survival (PFS) |
PFS was defined as the time from first dose of study treatment (ie, start date) to the date of progression of disease (PD) by RECIST v 1.1 or death due to any cause, whichever occurred first. PFS data was censored on the date of the last adequate tumor assessment for participants without an event (PD or death), for participants who started new anti-cancer treatment prior to an event, or for participants with an event after two or more missing tumor assessments. PD as per RECIST v1.1 for target lesions was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm. For non-target lesions PD was defined as unequivocal progression of pre-existing lesions. Analysis was performed using Kaplan-Meier method. |
From start of study treatment until first documentation of PD or death due to any cause or censoring date (maximum of 24 months) |
|
| Secondary |
Overall Survival |
Overall survival was defined as the time from the date of first study treatment to the date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan-Meier method. |
From date of start of study treatment until date of death or censoring date (maximum up to 56 months) |
|
| Secondary |
Maximum Observed Serum Concentration (Cmax) of Avelumab |
|
Pre-dose, 1 hour post-dose on Cycle 1 Day 1, Day 15 and Cycle 2 Day 1 |
|
| Secondary |
Cmax of Axitinib |
|
Pre-dose, 2 hour post-dose on Cycle 1 Day 15, Cycle 2 Day 1 and 15 |
|
| Secondary |
Pre-dose Observed Serum Concentration (Ctrough) of Avelumab |
|
Pre-dose on Cycle 1 Day 1, 15, Cycle 2 Day 1, Cycle 3 Day 15, Cycle 6 Day 15, Cycle 9 Day 15, and Cycle 12 Day 15 |
|
| Secondary |
Ctrough of Axitinib |
|
Pre-dose on Cycle 1 Day 15, Cycle 2 Day 1 and 15 |
|
| Secondary |
Number of Participants With Programmed Death-Ligand 1 (PD-L1) Status |
PD-L1 status was defined as positive when PD-L1 staining of any intensity was observed in >= 1% of the tumor cells. PD-L1 status was defined as negative when PD-L1 staining of any intensity was observed in < 1% of the tumor cells. |
Screening, up to 28 days prior to Day 1 |
|
| Secondary |
Tumour Mutational Burden (TMB) in Tumor Tissue |
Mutational load within tumor tissue was defined as number per megabase of the genome, coding, base substitution, and indel mutations present in the sample. Mutational load was determined in whole blood samples using next generation deoxyribonucleic acid (DNA) sequencing followed by computational analysis. |
Screening, up to 28 days prior to Day 1 |
|
| Secondary |
T-cell Receptor (TCR) Sequencing to Identify Fraction Productive of Cells |
The immune response was measured by total T cell receptor (TCR) sequencing in peripheral blood and determined the characterization of immune repertoires. Fraction productive of cells is defined as the number of T cells within the total nucleated cell count (T cells and non-T cells). |
Screening, up to 28 days prior to Day 1 |
|
| Secondary |
T-cell Receptor (TCR) Sequencing to Identify Simpson Clonality |
The immune response was measured by TCR sequencing in peripheral blood and determined the characterization of immune repertoires. Simpson clonality is calculated for a sample as the square root of Simpson's diversity index for all productive rearrangements. Values for clonality ranged from 0 to 1. Values near 1 represented samples with one or a few predominant rearrangements (monoclonal or oligoclonal samples) dominating the observed repertoire. Clonality values near 0 represented more polyclonal samples. |
Pre-dose on Day 1 of Cycle 1 |
|
| Secondary |
T-cell Receptor (TCR) Sequencing to Identify Total T Cells |
The immune response was measured by total TCR sequencing in peripheral blood and determined the characterization of immune repertoires. |
Pre-dose on Day 1 of Cycle 1 |
|
| Secondary |
Number of Participants With Positive Anti-drug Antibody (ADA) and Neutralizing Antibodies (nAb) Against Avelumab |
ADA and nAb positive was defined as presence of at least one positive ADA and nAb sample, respectively. NAb analysis was planned to be conducted for ADA positive samples. |
Within 2 hours pre-dose on Cycle 1 Day 1,15, Cycle 2 Day 1; Day 15 of Cycle 3, 6, 9, 12, end of treatment and 30 days after last dose of study treatment (maximum up to 56 months) |
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