Renal Cell Cancer
Conditions
Keywords
Cancer, renal cell cancer, kidney disease, kidney neoplasms, axitinib, sunitinib
Brief summary
This is a phase 3 randomized trial evaluating the anti-tumor activity and safety of avelumab in combination with axitinib and of sunitinib monotherapy, administered as first-line treatment, in patients with advanced renal cell carcinoma
Interventions
IV treatment Avelumab administered at 10 mg/kg IV every two weeks
Oral treatment Axitinib given 5 mg PO BID
DRUGSunitinib
Oral treatment Sunitinib given at 50 mg PO QD on schedule 4/2
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed advanced or metastatic RCC with clear cell component * Availability of a formalin-fixed, paraffin-embedded (FFPE) tumor tissue block from a de novo tumor biopsy during screening (biopsied tumor lesion should not be a RECIST target lesion). Alternatively, a recently obtained archival FFPE tumor tissue block (not cut slides) from a primary or metastatic tumor resection or biopsy can be provided if the following criteria are met: 1) the biopsy or resection was performed within 1 year of randomization AND 2) the patient has not received any intervening systemic anti-cancer treatment from the time the tissue was obtained and randomization onto the current study. If an FFPE tissue block cannot be provided as per documented regulations then, 15 unstained slides (10 minimum) will be acceptable * Availability of an archival FFPE tumor tissue from primary tumor resection specimen (if not provided per above). If an FFPE tissue block cannot be provided as per documented regulations 15 unstained slides (10 minimum) will be acceptable * At least one measurable lesion as defined by RECIST version 1.1 that has not been previously irradiated * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Adequate bone marrow function, renal and liver functions
Exclusion criteria
* Prior systemic therapy directed at advanced or metastatic RCC * Prior adjuvant or neoadjuvant therapy for RCC if disease progression or relapse has occurred during or within 12 months after the last dose of treatment. * Prior immunotherapy with IL-2, IFN-α, or anti PD 1, anti PD L1, anti PD L2, anti CD137, or anti cytotoxic T lymphocyte associated antigen 4 (CTLA 4) antibody (including ipilimumab), or any other antibody or drug specifically targeting T cell co stimulation or immune checkpoint pathways * Prior therapy with axitinib and/or sunitinib as well as any prior therapies with other VEGF pathway inhibitors * Newly diagnosed or active brain metastasis * Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3), any history of anaphylaxis, or uncontrolled asthma (ie, 3 or more features of partially controlled asthma Global Initiative for Asthma 2011) * Any of the following in the previous 12 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, LVEF less than LLN, clinically significant pericardial effusion, cerebrovascular accident, transient ischemic attack * Any of the following in the previous 6 months: deep vein thrombosis or symptomatic pulmonary embolism * Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines (for example, inactivated influenza vaccines)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) in Programmed Death-Ligand 1 (PD-L1) Positive Participants | From date of randomization to the first documentation of PD or death due to any cause or censoring date, whichever occurred first (maximum up to approximately 26 months) | PFS: time from the date of randomization to the date of the first documentation of progressive disease (PD) according to Response Evaluation Criteria in Solid Tumours (RECIST version \[v\] 1.1) or death due to any cause, whichever occurred first as assessed by BICR. PFS data was censored on date of last adequate tumor assessment for participants who did not have an event (PD or death), who started new anti-cancer therapy prior to an event or for participants with an event after 2 or more missing tumor assessments. PD was defined as at least a 20 percent (%), increase in the sum of all the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to relative increase of 20 %, sum must have also demonstrated an absolute more than (\>) of at least 5 millimeter (mm). The appearance of one or more new lesions was also considered progression. |
| Overall Survival (OS) in PD-L1 Positive Participants | From the date of randomization to the date of death due to any cause or censoring date, whichever occurred first (maximum up to approximately 89 months) | OS was defined as the time from the date of randomization 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Response (OR) as Assessed by BICR Irrespective of PD-L1 Expression | From date of randomization until PD (maximum up to approximately 26 months) | OR was defined as best overall response of complete response (CR) or partial response (PR) according to RECIST v1.1 as assessed by BICR recorded from date of randomization until disease progression. CR was defined as complete disappearance of all target and non-target lesions with the exception of nodal disease. All lymph nodes must decrease to normal size (short axis\<10 mm). All target lesions must be assessed. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. All target lesions must be assessed. 95% CI was based on Clopper-Pearson method. |
| Percentage of Participants With OR as Assessed by Investigator Irrespective of PD-L1 Expression | From date of randomization until PD (maximum up to approximately 89 months) | OR was defined as best overall response of CR or PR according to RECIST v1.1 as assessed by investigator recorded from date of randomization until disease progression. CR was defined as complete disappearance of all target and non-target lesions with the exception of nodal disease. All lymph nodes must decrease to normal size (short axis\<10 mm). All target lesions must be assessed. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. All target lesions must be assessed. 95% CI was based on Clopper-Pearson method. |
| Percentage of Participants With Disease Control (DC) as Assessed by BICR Irrespective of PD-L1 Expression | From date of randomization until PD (maximum up to approximately 26 months) | DC was defined as a best overall response of CR, PR, non-CR/non-PD or stable disease (SD) according to RECIST v1.1 as assessed by BICR. CR was defined as complete disappearance of all target and non-target lesions, with the exception of nodal disease and sustained for at least 4 weeks. All lymph nodes must decrease to normal size (short axis\<10mm). PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions. Non-CR/Non-PD was defined as persistence of any non-target lesions and/or tumor marker level above the normal limits. SD was defined as not to qualify for CR, PR or PD for target lesions and followed PR only if the sum increased by less than 20% from the nadir (smallest sum of diameters consider baseline and all assessments prior to the time point under evaluation), but enough that a previously documented 30% decrease no longer holds. |
| Percentage of Participants With DC as Assessed by Investigator Irrespective of PD-L1 Expression | From date of randomization until PD (maximum up to approximately 89 months) | DC was defined as a best overall response of CR, PR, non-CR/non-PD or SD according to RECIST v1.1 as assessed by investigator. CR was defined as complete disappearance of all target and non-target lesions, with the exception of nodal disease and sustained for at least 4 weeks. All lymph nodes must decrease to normal size (short axis\<10mm). PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions. Non-CR/Non-PD was defined as persistence of any non-target lesions and/or tumor marker level above the normal limits. SD was defined as not to qualify for CR, PR or PD for target lesions and followed PR only if the sum increased by less than 20% from the nadir (smallest sum of diameters consider baseline and all assessments prior to the time point under evaluation), but enough that a previously documented 30% decrease no longer holds. |
| Time to Tumor Response (TTR) as Assessed by BICR in Participants Irrespective of PD-L1 Expression | From the date of randomization to the first documentation of objective response (CR or PR) (maximum up to approximately 26 months) | TTR was defined as the time from randomization to the first documentation of objective tumor response according to RECIST v1.1 as assessed by BICR (CR or PR) which is subsequently confirmed. CR was defined as complete disappearance of all target and non-target lesions with the exception of nodal disease. All lymph nodes must decrease to normal size (short axis\<10 mm). All target lesions must be assessed. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. All target lesions must be assessed. |
| TTR as Assessed by Investigator in Participants Irrespective of PD-L1 Expression | From the date of randomization to the first documentation of objective response (CR or PR) (maximum up to approximately 89 months) | TTR was defined as the time from randomization to the first documentation of objective tumor response according to RECIST v1.1 as assessed by investigator (CR or PR) which is subsequently confirmed. CR was defined as complete disappearance of all target and non-target lesions with the exception of nodal disease. All lymph nodes must decrease to normal size (short axis\<10 mm). All target lesions must be assessed. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. All target lesions must be assessed. |
| Duration of Response (DR) as Assessed by BICR in Participants Irrespective of PD-L1 Expression | From documentation of OR until date of first documentation of PD or death due to any cause, whichever occurred first (maximum up to approximately 26 months) | BICR assessed DR: time from first documentation of OR (confirmed CR or PR) to date of first documentation of objective tumor progression assessed by BICR or death due to any cause whichever occurred first. As per RECIST v1.1. CR: complete disappearance of all target and non-target lesions with the exception of nodal disease. All lymph nodes must decrease to normal size (short axis\<10 mm). All target lesions must be assessed. PR: \>=30% decrease under baseline of the sum of diameters of all target measurable lesions. All target lesions must be assessed. PD: at least a 20% increase in the sum of all the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to relative increase of 20%, sum must have also demonstrated an absolute \> of at least 5 mm. The appearance of one or more new lesions was also considered progression. |
| DR as Assessed by Investigator in Participants Irrespective of PD-L1 Expression | From documentation of OR until date of first documentation of PD or death due to any cause, whichever occurred first (maximum up to approximately 89 months) | Investigator assessed DR: time from first documentation of OR (confirmed CR or PR) to date of first documentation of objective tumor progression (PD) assessed by investigator or death due to any cause whichever occurred first. As per RECIST v1.1. CR: complete disappearance of all target and non-target lesions with the exception of nodal disease. All lymph nodes must decrease to normal size (short axis\<10 mm). All target lesions must be assessed. PR: \>=30% decrease under baseline of the sum of diameters of all target measurable lesions. All target lesions must be assessed. PD: at least a 20% increase in the sum of all the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to relative increase of 20%, sum must have also demonstrated an absolute \> of at least 5 mm. The appearance of one or more new lesions was also considered progression. |
| PFS as Assessed by Investigator in Participants Irrespective of PD-L1 Expression | From date of randomization until PD, whichever occurred first (maximum up to approximately 89 months) | Investigator assessed PFS: time from the date of randomization to the date of the first documentation of PD according to RECIST v1.1 or death due to any cause, whichever occurred first. PFS data was censored on date of last adequate tumor assessment for participants who did not have an event (PD or death), who started new anti-cancer therapy prior to an event or for participants with an event after 2 or more missing tumor assessments. PD was defined as at least a 20% increase in the sum of all the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to relative increase of 20 %, sum must have also demonstrated an absolute \> of at least 5 mm. The appearance of one or more new lesions was also considered progression. |
| Progression-Free Survival on Next-line Therapy (PFS2) in Participants Irrespective of PD-L1 Expression | From date of randomization until PD or death, whichever occurred first (maximum up to approximately 89 months) | PFS2 is defined as the time (in months) from randomization to discontinuation of next-line treatment after first objective disease progression by investigator assessment, second objective disease progression by investigator assessment after initiation of next-line treatment, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of all the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to relative increase of 20 %, sum must have also demonstrated an absolute \> of at least 5 mm. The appearance of one or more new lesions was also considered progression. |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) Graded Based on National Cancer Institute -Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (V) 4.03 | From start of study treatment until 90 days after last dose of study treatment (maximum up to approximately 92 months) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were those events with onset dates occurring during the on-treatment period for the first time, or if the worsening of an event was during the on-treatment period (time from the first dose of study treatment through 90 days after last dose of study treatment or start day of new anti-cancer drug therapy-1 day). As per NCI-CTCAE v4.03, grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening consequences and grade 5=death. |
| Number of Participants According to Grade Shift in Hematology Parameters | From start of study treatment until 90 days after last dose of study treatment (maximum up to approximately 92 months) | Following hematology parameters were assessed: hemoglobin decreased (anemia), hemoglobin increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased and white blood cell (WBC) decreased. Laboratory abnormalities were graded as per NCI- CTCAE v 4.03 where, grade(G) 0= non-missing lab value that does not meet either of G1 through 4 criteria, G1=mild, G2=moderate, G3=severe, G4=life-threatening consequences and G5=death. Baseline was defined as last assessment prior to first dose of study treatment. Number of participants with a baseline grade of 0 to 4 which shifted to G3-4 post-baseline are reported in this outcome measure. Only non-zero categories for any reporting arm are reported. |
| Number of Participants According to Grade Shift in Chemistry Parameters | From start of study treatment until 90 days after last dose of study treatment (maximum up to approximately 92 months) | Following chemistry parameters were assessed: alanine aminotransferase(ALT) increased, alkaline phosphatase(ALP) increased, aspartate aminotransferase(AST) increased, blood bilirubin increased, cholesterol high, creatinine phosphokinase(CPK) increased, creatinine increased, gamma glutamyl transferase(GGT) increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesmia, hypernatremia, hypertriglyceridemia, hypoalbuminemia, hypokalemia, hypomagnesemia, hyponatremia, lipase increased and serum amylase increased. Laboratory abnormality graded as per NCI CTCAE v4.03; G0=non-missing lab value that does not meet either of G1 through 4 criteria, G1=mild, G2=moderate, G3=severe, G4=life-threatening consequences and G5=death. Number of participants with a baseline grade of 0 to 4 which shifted to G3-4 post-baseline are reported. Only non-zero categories for any reporting arm are reported. |
| Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Baseline (pre-dose on Day 1 of Cycle 1), Day 1 of Cycle 2, 3, 4, 5, 6, 7, EOT visit (maximum up to approximately 89 months) (each cycle=42 days) | Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured with the participant in the seated position after the participant had been sitting quietly for at least 5 minutes. |
| Change From Baseline in Vital Signs - Pulse Rate at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and EOT Visit | Baseline (pre-dose on Day 1 of Cycle 1), Day 1 of Cycle 2, 3, 4, 5, 6, 7, EOT visit (maximum up to approximately 89 months) (each cycle=42 days) | Pulse rate was measured with the participant in the seated position after the participant had been sitting quietly for at least 5 minutes. |
| PFS as Assessed by BICR in Participants Irrespective of PD-L1 Expression | From date of randomization to the first documentation of PD or death due to any cause or censoring date, whichever occurred first (maximum up to approximately 26 months) | PFS: time from the date of randomization to the date of the first documentation of PD or death due to any cause, whichever occurred first as assessed by BICR. PFS data was censored on date of last adequate tumor assessment for participants who did not have an event (PD or death), who started new anti-cancer therapy prior to an event or for participants with an event after 2 or more missing tumor assessments. PD was defined as at least a 20% increase in the sum of all the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to relative increase of 20 %, sum must have also demonstrated an absolute \> of at least 5 mm. The appearance of one or more new lesions was also considered progression. |
| Time to Treatment Discontinuation/Failure Due to Toxicity | From first dose of study treatment until discontinuation of study treatment (maximum up to approximately 89 months) | Time to treatment discontinuation/ failure due to toxicity was defined as the time from first dose of study treatment to discontinuation of study treatment due to an adverse event or death due to study treatment toxicity. |
| Trough Plasma Concentration (Ctrough) of Avelumab | Pre dose (0 hour) on Day 1, 15 and 29 of Cycle 1, Day 1 and 29 of Cycles 2, 3, 4 and Day 1 of Cycle 6 | Predose concentration during multiple dosing. |
| Ctrough of Axitinib | Pre dose (0 hour) on day 15 and 29 of cycle 1 (each cycle= 6 weeks) | Predose concentration during multiple dosing. |
| Maximum Plasma Concentration (Cmax) of Axitinib | 2 hours post-dose on Day 1, pre-dose and 2 hours post dose on Days 15 and 29 of Cycle 1 | — |
| Number of Participants With Positive PD-L1 Biomarker Expression in Pre-treatment Tumor Tissue | At screening | Tumor biospecimens from pre-treatment tissue samples were analyzed by immunohistochemistry for PD-L1 biomarker expression. Number of participants with positive PD-L1 biomarker expression are reported in this outcome measure. |
| PFS in PD-L1 Biomarker-Positive and PD-L1 Biomarker-Negative Subgroups | From date of randomization to the first documentation of PD or death due to any cause or censoring date, whichever occurred first (maximum up to approximately 26 months) | PFS: time from the date of randomization to the date of the first documentation of PD according to RECIST v1.1 or death due to any cause, whichever occurred first. PFS data was censored on date of last adequate tumor assessment for participants who did not have an event (PD or death), who started new anti-cancer therapy prior to an event or for participants with an event after 2 or more missing tumor assessments. PD was defined as at least a 20% increase in the sum of all the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to relative increase of 20 %, sum must have also demonstrated an absolute \> of at least 5 mm. The appearance of one or more new lesions was also considered progression. |
| Percentage of Participants With OR in PD-L1 Biomarker-Positive and PD-L1 Biomarker-Negative Subgroups | From date of randomization until PD (maximum up to approximately 26 months) | OR was defined as best overall response of CR or PR according to RECIST v1.1 as assessed by BICR recorded from date of randomization until disease progression. CR was defined as complete disappearance of all target and non-target lesions with the exception of nodal disease. All lymph nodes must decrease to normal size (short axis\<10 mm). All target lesions must be assessed. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. All target lesions must be assessed. |
| Percentage of Participants With DC in Biomarker-Positive Subgroup | From date of randomization until PD or death, whichever occurred first (maximum up to approximately 26 months) | DC was defined as a best overall response of CR, PR, or stable disease (SD) according to the RECIST v.1.1 recorded from randomization until disease progression or death due to any cause, whichever occurred first. CR was defined as complete disappearance of all target and non-target lesions with the exception of nodal disease. All lymph nodes must decrease to normal size (short axis\<10 mm). All target lesions must be assessed. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. All target lesions must be assessed. SD was defined as PR that the sum increases by less than 20% from the nadir, (smallest sum of diameters consider baseline and all assessments prior to the time point under evaluation), but enough that a previously documented 30% decrease no longer holds. |
| TTR in Biomarker-Positive Subgroup | From the date of randomization to the first documentation of objective response (CR or PR) (maximum up to approximately 26 months) | TTR was defined as the time from randomization to the first documentation of objective tumor response (CR or PR) according to RECIST v1.1 which is subsequently confirmed. CR was defined as complete disappearance of all target and non-target lesions with the exception of nodal disease. All lymph nodes must decrease to normal size (short axis\<10 mm). All target lesions must be assessed. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. All target lesions must be assessed. |
| DR in PD-L1 Biomarker-Positive and PD-L1 Biomarker-Negative Subgroups | From documentation of OR until date of first documentation of PD or death due to any cause, whichever occurred first (maximum up to approximately 26 months) | DR: time from first documentation of OR (confirmed CR or PR) to date of first documentation of PD or death due to any cause, whichever occurred first. As per RECIST version 1.1, CR: disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (target or non-target) must have reduction in short axis to \<10 mm. PR: at least 30%\< in sum of longest dimensions of target lesions taking as reference baseline sum longest dimensions. PD: defined as at least a 20% \> in sum of diameters of target lesions, taking as reference the smallest sum on study (this included baseline sum if that is smallest on study). In addition to relative increase of 20%, sum must have also demonstrated an absolute increase of at least 5 mm. Appearance of one or more new lesions was also considered progression. |
| Number of Participants With Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb) of Avelumab When Used in Combination With Axitinib | From start of treatment until 30 days after the end of avelumab treatment (maximum up to approximately 89 months) | — |
| Time to Symptom Deterioration (TTD) for Functional Assessment of Cancer Therapy (FACT)-Kidney Symptom Index - Disease Related Symptoms (FKSI-DRS) | Date of randomization to the first time the participant's score showed a 3-point or greater decrease in FKSI-DRS (maximum up to approximately 26 months) | TTD was defined as the time from date of randomization to the first time the participant's score showed a 3-point or greater decrease in FKSI-DRS. FKSI was used to assess symptoms and quality of life (QoL) for those diagnosed with advanced kidney cancer and it consisted of 19 questions. A 9-item subscale of the FKSI known as FKSI-Disease Related Symptoms subscale (FKSI-DRS). This subscale included 9 items: lack of energy, pain, losing weight, bone pain, fatigue, shortness of breath, coughing, bothered by fevers, and hematuria. Each of the 9 items was answered on a 5-point Likert-type scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI-DRS score = sum of the 9 item scores; total range: 0 - 36; 0 (no symptoms) to 36 (very much); higher score indicated greater presence of symptoms. |
| Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Baseline, Day 1 of Cycle 2 to Cycle 60, End of treatment (any Day from Day 1 of dosing; maximum up to approximately 89 months) | EQ-5D-5L is a 5-item participant-completed questionnaire designed to assess health status in terms of a single utility score. EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Overall scores ranged from 0 to 1, with low scores representing a higher level of dysfunction. Published UK weights were used to create a single summary utility score. Utility scores range from -0.594 to 1, with higher scores representing better health status. |
| Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Baseline, Day 1 of Cycle 2 to Cycle 60, End of treatment (any Day from Day 1 of dosing; maximum up to approximately 89 months) | EQ-VAS records the participant's self-rated health status from 0 (worst imaginable health status) to 100 (best imaginable health status), where higher scores indicated better health status. |
| Number of Participants Who Discontinued Treatment Due to Toxicity | From first dose of study treatment until discontinuation of study treatment (maximum up to approximately 89 months) | Number of participants who discontinued treatment due to toxicity are reported in this outcome measure. |
| OS in Participants Irrespective of PD-L1 Expression | From the date of randomization to the date of death due to any cause or censoring date, whichever occurred first (maximum up to approximately 89 months) | OS was defined as the time (in months) from the date of randomization 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. |
Countries
Australia, Austria, Belgium, Canada, Denmark, France, Germany, Hungary, Israel, Italy, Japan, Mexico, Netherlands, New Zealand, Romania, Russia, South Korea, Spain, Sweden, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 886 participants were enrolled and randomized in the study.
Participants by arm
| Arm | Count |
|---|---|
| Avelumab + Axitinib Participants with aRCC received avelumab 10 mg/kg, IV at Q2W in a 6-week cycle plus axitinib 5 mg, orally BID. Each treatment cycle was of 42 days. | 442 |
| Sunitinib Participants with aRCC received sunitinib 50 mg orally, QD on a schedule of 4 weeks on treatment followed by 2 weeks off treatment (schedule 4/2 in 6-week cycles). Each treatment cycle was of 42 days. | 444 |
| Total | 886 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 86 | 65 |
| Overall Study | Death | 25 | 22 |
| Overall Study | Global deterioration of health status | 18 | 20 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | No longer met eligibility criteria | 6 | 2 |
| Overall Study | Non-compliance with study drug | 1 | 1 |
| Overall Study | Other | 18 | 6 |
| Overall Study | Participation terminated by sponsor | 6 | 9 |
| Overall Study | Physician Decision | 15 | 8 |
| Overall Study | Progressive disease | 236 | 266 |
| Overall Study | Protocol Violation | 2 | 1 |
| Overall Study | Withdrawal by Subject | 29 | 43 |
Baseline characteristics
| Characteristic | Sunitinib | Total | Avelumab + Axitinib |
|---|---|---|---|
| Age, Continuous | 60.66 Years STANDARD_DEVIATION 10.28 | 60.76 Years STANDARD_DEVIATION 10.11 | 60.86 Years STANDARD_DEVIATION 9.95 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants | 37 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 377 Participants | 765 Participants | 388 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 49 Participants | 84 Participants | 35 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants | 8 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 63 Participants | 133 Participants | 70 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 20 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 32 Participants | 58 Participants | 26 Participants |
| Race (NIH/OMB) White | 334 Participants | 666 Participants | 332 Participants |
| Sex: Female, Male Female | 100 Participants | 226 Participants | 126 Participants |
| Sex: Female, Male Male | 344 Participants | 660 Participants | 316 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 284 / 442 | 296 / 444 |
| other Total, other adverse events | 429 / 434 | 433 / 439 |
| serious Total, serious adverse events | 231 / 434 | 166 / 439 |
Outcome results
Primary
Overall Survival (OS) in PD-L1 Positive Participants
OS was defined as the time from the date of randomization 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.
Time frame: From the date of randomization to the date of death due to any cause or censoring date, whichever occurred first (maximum up to approximately 89 months)
Population: FAS included all participants who are randomized. Analysis was performed on subset of randomized participants, who were PD-L1 positive.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Avelumab + Axitinib | Overall Survival (OS) in PD-L1 Positive Participants | 43.2 Months |
| Sunitinib | Overall Survival (OS) in PD-L1 Positive Participants | 36.2 Months |
p-value: 0.150995% CI: [0.701, 1.057]Log Rank
Primary
Progression Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) in Programmed Death-Ligand 1 (PD-L1) Positive Participants
PFS: time from the date of randomization to the date of the first documentation of progressive disease (PD) according to Response Evaluation Criteria in Solid Tumours (RECIST version \[v\] 1.1) or death due to any cause, whichever occurred first as assessed by BICR. PFS data was censored on date of last adequate tumor assessment for participants who did not have an event (PD or death), who started new anti-cancer therapy prior to an event or for participants with an event after 2 or more missing tumor assessments. PD was defined as at least a 20 percent (%), increase in the sum of all the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to relative increase of 20 %, sum must have also demonstrated an absolute more than (\>) of at least 5 millimeter (mm). The appearance of one or more new lesions was also considered progression.
Time frame: From date of randomization to the first documentation of PD or death due to any cause or censoring date, whichever occurred first (maximum up to approximately 26 months)
Population: FAS included all participants who were randomized. Analysis was performed on subset of randomized participants, who were PD-L1 positive.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Avelumab + Axitinib | Progression Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) in Programmed Death-Ligand 1 (PD-L1) Positive Participants | 13.8 Months |
| Sunitinib | Progression Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) in Programmed Death-Ligand 1 (PD-L1) Positive Participants | 7.2 Months |
p-value: 0.000195% CI: [0.475, 0.79]Log Rank
Secondary
Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score
EQ-VAS records the participant's self-rated health status from 0 (worst imaginable health status) to 100 (best imaginable health status), where higher scores indicated better health status.
Time frame: Baseline, Day 1 of Cycle 2 to Cycle 60, End of treatment (any Day from Day 1 of dosing; maximum up to approximately 89 months)
Population: FAS included all randomized participants. All participants reported under Number of Participants Analyzed contributed data to the table; however, may not have evaluable data for every row. Number Analyzed signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 32 (Day 1) | 5.4 Units on a scale | Standard Deviation 16.35 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 10 (Day 1) | 1.6 Units on a scale | Standard Deviation 15.12 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 33 (Day 1) | 5.5 Units on a scale | Standard Deviation 16.07 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 18 (Day 1) | 3.2 Units on a scale | Standard Deviation 15.31 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 34 (Day 1) | 4.8 Units on a scale | Standard Deviation 15.25 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 3 (Day 1) | -0.4 Units on a scale | Standard Deviation 16.39 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 35 (Day 1) | 6.0 Units on a scale | Standard Deviation 14.53 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 19 (Day 1) | 4.5 Units on a scale | Standard Deviation 15.61 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 36 (Day 1) | 6.0 Units on a scale | Standard Deviation 15.63 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 11 (Day 1) | 2.5 Units on a scale | Standard Deviation 15.7 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 37 (Day 1) | 5.8 Units on a scale | Standard Deviation 14.63 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 20 (Day 1) | 3.9 Units on a scale | Standard Deviation 15.15 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 38 (Day 1) | 5.3 Units on a scale | Standard Deviation 14.58 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 7 (Day 1) | 1.2 Units on a scale | Standard Deviation 16.34 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 39 (Day 1) | 5.3 Units on a scale | Standard Deviation 14.04 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 21 (Day 1) | 3.7 Units on a scale | Standard Deviation 16.3 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 40 (Day 1) | 6.0 Units on a scale | Standard Deviation 15 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 12 (Day 1) | 2.1 Units on a scale | Standard Deviation 14.72 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 41 (Day 1) | 5.6 Units on a scale | Standard Deviation 13.69 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 22 (Day 1) | 4.3 Units on a scale | Standard Deviation 16.43 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 42 (Day 1) | 5.3 Units on a scale | Standard Deviation 13.68 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 5 (Day 1) | 0.4 Units on a scale | Standard Deviation 16.66 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 43 (Day 1) | 6.6 Units on a scale | Standard Deviation 11.64 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 23 (Day 1) | 3.7 Units on a scale | Standard Deviation 16.9 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 44 (Day 1) | 4.9 Units on a scale | Standard Deviation 13.38 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 13 (Day 1) | 3.0 Units on a scale | Standard Deviation 14.39 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 45 (Day 1) | 6.3 Units on a scale | Standard Deviation 12.55 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 24 (Day 1) | 3.3 Units on a scale | Standard Deviation 18.7 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 46 (Day 1) | 6.7 Units on a scale | Standard Deviation 13.25 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 8 (Day 1) | 1.4 Units on a scale | Standard Deviation 16.54 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 47 (Day 1) | 5.4 Units on a scale | Standard Deviation 11.1 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 25 (Day 1) | 4.6 Units on a scale | Standard Deviation 15.28 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 48 (Day 1) | 4.4 Units on a scale | Standard Deviation 11.73 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 14 (Day 1) | 2.7 Units on a scale | Standard Deviation 15.07 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 49 (Day 1) | 4.2 Units on a scale | Standard Deviation 12.21 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 26 (Day 1) | 4.4 Units on a scale | Standard Deviation 17.1 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 50 (Day 1) | 4.8 Units on a scale | Standard Deviation 13.07 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 4 (Day 1) | -0.1 Units on a scale | Standard Deviation 17.23 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 51 (Day 1) | 5.8 Units on a scale | Standard Deviation 12.36 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 27 (Day 1) | 4.7 Units on a scale | Standard Deviation 16.59 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 52 (Day 1) | 4.2 Units on a scale | Standard Deviation 11.37 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 15 (Day 1) | 3.1 Units on a scale | Standard Deviation 14.97 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 53 (Day 1) | 3.2 Units on a scale | Standard Deviation 11.43 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 28 (Day 1) | 6.3 Units on a scale | Standard Deviation 16.08 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 54 (Day 1) | 4.6 Units on a scale | Standard Deviation 11.54 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 9 (Day 1) | 2.0 Units on a scale | Standard Deviation 16.06 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 55 (Day 1) | 4.6 Units on a scale | Standard Deviation 11.65 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 29 (Day 1) | 4.8 Units on a scale | Standard Deviation 15.44 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 56 (Day 1) | -0.6 Units on a scale | Standard Deviation 8.08 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 16 (Day 1) | 2.9 Units on a scale | Standard Deviation 15.08 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 57 (Day 1) | -1.9 Units on a scale | Standard Deviation 10.67 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 30 (Day 1) | 6.0 Units on a scale | Standard Deviation 15.78 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 58 (Day 1) | -2.1 Units on a scale | Standard Deviation 8.59 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 6 (Day 1) | 1.3 Units on a scale | Standard Deviation 16.05 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 59 (Day 1) | 0.0 Units on a scale | Standard Deviation 9.35 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 60 (Day 1) | -1.7 Units on a scale | Standard Deviation 16.07 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | End of treatment | -5.0 Units on a scale | Standard Deviation 19.92 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 2 (Day 1) | -0.9 Units on a scale | Standard Deviation 16.12 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 31 (Day 1) | 5.7 Units on a scale | Standard Deviation 15.42 |
| Avelumab + Axitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 17 (Day 1) | 3.0 Units on a scale | Standard Deviation 15.44 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | End of treatment | -4.3 Units on a scale | Standard Deviation 19.63 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 2 (Day 1) | -0.2 Units on a scale | Standard Deviation 15.85 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 3 (Day 1) | 0.4 Units on a scale | Standard Deviation 16.44 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 4 (Day 1) | 0.7 Units on a scale | Standard Deviation 17.26 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 5 (Day 1) | 1.8 Units on a scale | Standard Deviation 16.16 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 6 (Day 1) | 2.6 Units on a scale | Standard Deviation 15.35 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 7 (Day 1) | 3.3 Units on a scale | Standard Deviation 14.91 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 8 (Day 1) | 2.9 Units on a scale | Standard Deviation 13.84 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 9 (Day 1) | 3.3 Units on a scale | Standard Deviation 13.77 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 10 (Day 1) | 2.4 Units on a scale | Standard Deviation 14.46 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 11 (Day 1) | 4.1 Units on a scale | Standard Deviation 12.91 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 12 (Day 1) | 2.6 Units on a scale | Standard Deviation 14.59 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 13 (Day 1) | 2.7 Units on a scale | Standard Deviation 14.29 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 14 (Day 1) | 3.0 Units on a scale | Standard Deviation 13.98 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 15 (Day 1) | 4.7 Units on a scale | Standard Deviation 13.63 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 16 (Day 1) | 3.6 Units on a scale | Standard Deviation 14.02 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 17 (Day 1) | 3.2 Units on a scale | Standard Deviation 12.88 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 18 (Day 1) | 2.0 Units on a scale | Standard Deviation 13.69 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 19 (Day 1) | 3.0 Units on a scale | Standard Deviation 13.1 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 20 (Day 1) | 3.1 Units on a scale | Standard Deviation 12.58 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 21 (Day 1) | 2.1 Units on a scale | Standard Deviation 13 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 22 (Day 1) | 2.6 Units on a scale | Standard Deviation 12.82 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 23 (Day 1) | 1.3 Units on a scale | Standard Deviation 15.16 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 24 (Day 1) | 4.5 Units on a scale | Standard Deviation 13.45 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 25 (Day 1) | 4.2 Units on a scale | Standard Deviation 14.42 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 26 (Day 1) | 3.4 Units on a scale | Standard Deviation 13 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 27 (Day 1) | 5.4 Units on a scale | Standard Deviation 13.43 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 28 (Day 1) | 5.0 Units on a scale | Standard Deviation 13.84 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 29 (Day 1) | 5.4 Units on a scale | Standard Deviation 14.24 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 30 (Day 1) | 5.3 Units on a scale | Standard Deviation 14.61 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 31 (Day 1) | 5.2 Units on a scale | Standard Deviation 14.88 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 32 (Day 1) | 6.0 Units on a scale | Standard Deviation 13.57 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 33 (Day 1) | 3.6 Units on a scale | Standard Deviation 20.61 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 34 (Day 1) | 6.1 Units on a scale | Standard Deviation 15.91 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 35 (Day 1) | 6.4 Units on a scale | Standard Deviation 15.61 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 36 (Day 1) | 5.2 Units on a scale | Standard Deviation 17.11 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 37 (Day 1) | 4.5 Units on a scale | Standard Deviation 15.86 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 38 (Day 1) | 4.3 Units on a scale | Standard Deviation 17.58 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 39 (Day 1) | 5.9 Units on a scale | Standard Deviation 15.75 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 40 (Day 1) | 4.7 Units on a scale | Standard Deviation 18.17 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 41 (Day 1) | 6.2 Units on a scale | Standard Deviation 18.37 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 42 (Day 1) | 5.4 Units on a scale | Standard Deviation 18.19 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 43 (Day 1) | 5.4 Units on a scale | Standard Deviation 20.14 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 44 (Day 1) | 5.1 Units on a scale | Standard Deviation 19.77 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 45 (Day 1) | 1.5 Units on a scale | Standard Deviation 17.97 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 46 (Day 1) | 0.3 Units on a scale | Standard Deviation 19.31 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 47 (Day 1) | 2.5 Units on a scale | Standard Deviation 18.07 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 48 (Day 1) | 3.5 Units on a scale | Standard Deviation 21.77 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 49 (Day 1) | 1.9 Units on a scale | Standard Deviation 21.42 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 50 (Day 1) | 2.9 Units on a scale | Standard Deviation 20.53 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 51 (Day 1) | 2.1 Units on a scale | Standard Deviation 22.93 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 52 (Day 1) | 1.5 Units on a scale | Standard Deviation 19.94 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 53 (Day 1) | 7.7 Units on a scale | Standard Deviation 16.22 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 54 (Day 1) | 7.5 Units on a scale | Standard Deviation 13.34 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 55 (Day 1) | 7.8 Units on a scale | Standard Deviation 17.89 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 56 (Day 1) | -6.0 Units on a scale | Standard Deviation 5.66 |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 57 (Day 1) | -2.0 Units on a scale | — |
| Sunitinib | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Score | Cycle 58 (Day 1) | -2.0 Units on a scale | — |
Secondary
Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score
EQ-5D-5L is a 5-item participant-completed questionnaire designed to assess health status in terms of a single utility score. EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Overall scores ranged from 0 to 1, with low scores representing a higher level of dysfunction. Published UK weights were used to create a single summary utility score. Utility scores range from -0.594 to 1, with higher scores representing better health status.
Time frame: Baseline, Day 1 of Cycle 2 to Cycle 60, End of treatment (any Day from Day 1 of dosing; maximum up to approximately 89 months)
Population: FAS included all randomized participants. All participants reported under Number of Participants Analyzed contributed data to the table; however, may not have evaluable data for every row. Number Analyzed signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 32 (Day 1) | -0.044 Units on a scale | Standard Deviation 0.2095 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 10 (Day 1) | -0.025 Units on a scale | Standard Deviation 0.1935 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 33 (Day 1) | -0.051 Units on a scale | Standard Deviation 0.2294 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 18 (Day 1) | -0.040 Units on a scale | Standard Deviation 0.1667 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 34 (Day 1) | -0.029 Units on a scale | Standard Deviation 0.1776 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 3 (Day 1) | -0.023 Units on a scale | Standard Deviation 0.1826 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 35 (Day 1) | -0.010 Units on a scale | Standard Deviation 0.1442 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 19 (Day 1) | -0.059 Units on a scale | Standard Deviation 0.1959 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 36 (Day 1) | -0.016 Units on a scale | Standard Deviation 0.1599 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 11 (Day 1) | -0.020 Units on a scale | Standard Deviation 0.1854 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 37 (Day 1) | -0.027 Units on a scale | Standard Deviation 0.1507 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 20 (Day 1) | -0.050 Units on a scale | Standard Deviation 0.1942 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 38 (Day 1) | -0.016 Units on a scale | Standard Deviation 0.1459 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 7 (Day 1) | -0.018 Units on a scale | Standard Deviation 0.1651 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 39 (Day 1) | -0.042 Units on a scale | Standard Deviation 0.1569 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 21 (Day 1) | -0.048 Units on a scale | Standard Deviation 0.1902 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 40 (Day 1) | -0.021 Units on a scale | Standard Deviation 0.1484 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 12 (Day 1) | -0.026 Units on a scale | Standard Deviation 0.1875 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 41 (Day 1) | -0.030 Units on a scale | Standard Deviation 0.1492 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 22 (Day 1) | 0.037 Units on a scale | Standard Deviation 0.1919 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 42 (Day 1) | -0.021 Units on a scale | Standard Deviation 0.1634 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 5 (Day 1) | -0.019 Units on a scale | Standard Deviation 0.1622 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 43 (Day 1) | -0.031 Units on a scale | Standard Deviation 0.1334 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 23 (Day 1) | -0.033 Units on a scale | Standard Deviation 0.2021 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 44 (Day 1) | -0.028 Units on a scale | Standard Deviation 0.13 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 13 (Day 1) | -0.026 Units on a scale | Standard Deviation 0.1777 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 45 (Day 1) | -0.050 Units on a scale | Standard Deviation 0.1442 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 24 (Day 1) | -0.036 Units on a scale | Standard Deviation 0.1982 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 46 (Day 1) | -0.042 Units on a scale | Standard Deviation 0.138 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 8 (Day 1) | -0.029 Units on a scale | Standard Deviation 0.1848 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 47 (Day 1) | -0.019 Units on a scale | Standard Deviation 0.124 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 25 (Day 1) | -0.019 Units on a scale | Standard Deviation 0.1825 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 48 (Day 1) | -0.025 Units on a scale | Standard Deviation 0.1566 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 14 (Day 1) | -0.036 Units on a scale | Standard Deviation 0.1938 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 49 (Day 1) | -0.028 Units on a scale | Standard Deviation 0.1356 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 26 (Day 1) | -0.039 Units on a scale | Standard Deviation 0.1927 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 50 (Day 1) | -0.028 Units on a scale | Standard Deviation 0.1359 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 4 (Day 1) | -0.029 Units on a scale | Standard Deviation 0.1829 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 51 (Day 1) | -0.011 Units on a scale | Standard Deviation 0.1304 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 27 (Day 1) | -0.046 Units on a scale | Standard Deviation 0.2233 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 52 (Day 1) | -0.036 Units on a scale | Standard Deviation 0.1265 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 15 (Day 1) | -0.036 Units on a scale | Standard Deviation 0.1892 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 53 (Day 1) | -0.084 Units on a scale | Standard Deviation 0.1437 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 28 (Day 1) | -0.039 Units on a scale | Standard Deviation 0.206 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 54 (Day 1) | -0.040 Units on a scale | Standard Deviation 0.1425 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 9 (Day 1) | -0.029 Units on a scale | Standard Deviation 0.2021 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 55 (Day 1) | -0.046 Units on a scale | Standard Deviation 0.1121 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 29 (Day 1) | -0.019 Units on a scale | Standard Deviation 0.2095 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 56 (Day 1) | -0.083 Units on a scale | Standard Deviation 0.1081 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 16 (Day 1) | -0.044 Units on a scale | Standard Deviation 0.1757 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 57 (Day 1) | -0.104 Units on a scale | Standard Deviation 0.1347 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 30 (Day 1) | -0.032 Units on a scale | Standard Deviation 0.2244 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 58 (Day 1) | -0.078 Units on a scale | Standard Deviation 0.1408 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 6 (Day 1) | -0.025 Units on a scale | Standard Deviation 0.1787 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 59 (Day 1) | -0.106 Units on a scale | Standard Deviation 0.1053 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 60 (Day 1) | -0.040 Units on a scale | Standard Deviation 0.1167 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | End of Treatment | -0.111 Units on a scale | Standard Deviation 0.2464 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 2 (Day 1) | -0.034 Units on a scale | Standard Deviation 0.1743 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 31 (Day 1) | -0.042 Units on a scale | Standard Deviation 0.2246 |
| Avelumab + Axitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 17 (Day 1) | -0.050 Units on a scale | Standard Deviation 0.195 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | End of Treatment | -0.069 Units on a scale | Standard Deviation 0.2375 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 2 (Day 1) | 0.001 Units on a scale | Standard Deviation 0.1632 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 3 (Day 1) | -0.017 Units on a scale | Standard Deviation 0.1804 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 4 (Day 1) | -0.022 Units on a scale | Standard Deviation 0.1667 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 5 (Day 1) | -0.016 Units on a scale | Standard Deviation 0.1826 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 6 (Day 1) | -0.003 Units on a scale | Standard Deviation 0.1967 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 7 (Day 1) | 0.008 Units on a scale | Standard Deviation 0.1618 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 8 (Day 1) | 0.002 Units on a scale | Standard Deviation 0.1731 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 9 (Day 1) | -0.011 Units on a scale | Standard Deviation 0.1662 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 10 (Day 1) | -0.018 Units on a scale | Standard Deviation 0.1617 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 11 (Day 1) | 0.004 Units on a scale | Standard Deviation 0.1642 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 12 (Day 1) | -0.016 Units on a scale | Standard Deviation 0.1712 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 13 (Day 1) | -0.017 Units on a scale | Standard Deviation 0.1549 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 14 (Day 1) | -0.006 Units on a scale | Standard Deviation 0.16 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 15 (Day 1) | 0.018 Units on a scale | Standard Deviation 0.1487 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 16 (Day 1) | 0.020 Units on a scale | Standard Deviation 0.1663 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 17 (Day 1) | -0.000 Units on a scale | Standard Deviation 0.1675 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 18 (Day 1) | -0.027 Units on a scale | Standard Deviation 0.1765 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 19 (Day 1) | 0.003 Units on a scale | Standard Deviation 0.1665 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 20 (Day 1) | 0.001 Units on a scale | Standard Deviation 0.1538 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 21 (Day 1) | -0.004 Units on a scale | Standard Deviation 0.1904 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 22 (Day 1) | 0.002 Units on a scale | Standard Deviation 0.1561 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 23 (Day 1) | -0.028 Units on a scale | Standard Deviation 0.1729 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 24 (Day 1) | 0.004 Units on a scale | Standard Deviation 0.1618 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 25 (Day 1) | -0.007 Units on a scale | Standard Deviation 0.1678 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 26 (Day 1) | -0.009 Units on a scale | Standard Deviation 0.1471 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 27 (Day 1) | 0.014 Units on a scale | Standard Deviation 0.1492 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 28 (Day 1) | -0.007 Units on a scale | Standard Deviation 0.1639 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 29 (Day 1) | 0.017 Units on a scale | Standard Deviation 0.1601 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 30 (Day 1) | -0.003 Units on a scale | Standard Deviation 0.1557 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 31 (Day 1) | -0.009 Units on a scale | Standard Deviation 0.1508 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 32 (Day 1) | 0.032 Units on a scale | Standard Deviation 0.1255 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 33 (Day 1) | -0.060 Units on a scale | Standard Deviation 0.355 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 34 (Day 1) | 0.038 Units on a scale | Standard Deviation 0.1558 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 35 (Day 1) | -0.002 Units on a scale | Standard Deviation 0.161 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 36 (Day 1) | 0.030 Units on a scale | Standard Deviation 0.1551 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 37 (Day 1) | 0.052 Units on a scale | Standard Deviation 0.1601 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 38 (Day 1) | 0.057 Units on a scale | Standard Deviation 0.1666 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 39 (Day 1) | 0.052 Units on a scale | Standard Deviation 0.1386 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 40 (Day 1) | 0.060 Units on a scale | Standard Deviation 0.1232 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 41 (Day 1) | 0.056 Units on a scale | Standard Deviation 0.1853 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 42 (Day 1) | 0.034 Units on a scale | Standard Deviation 0.1585 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 43 (Day 1) | 0.011 Units on a scale | Standard Deviation 0.2062 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 44 (Day 1) | 0.016 Units on a scale | Standard Deviation 0.2114 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 45 (Day 1) | 0.007 Units on a scale | Standard Deviation 0.2191 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 46 (Day 1) | -0.007 Units on a scale | Standard Deviation 0.2495 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 47 (Day 1) | -0.015 Units on a scale | Standard Deviation 0.2335 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 48 (Day 1) | 0.009 Units on a scale | Standard Deviation 0.2833 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 49 (Day 1) | 0.010 Units on a scale | Standard Deviation 0.1873 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 50 (Day 1) | 0.028 Units on a scale | Standard Deviation 0.2507 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 51 (Day 1) | -0.010 Units on a scale | Standard Deviation 0.2594 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 52 (Day 1) | -0.035 Units on a scale | Standard Deviation 0.2524 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 53 (Day 1) | 0.048 Units on a scale | Standard Deviation 0.1308 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 54 (Day 1) | 0.078 Units on a scale | Standard Deviation 0.1157 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 55 (Day 1) | 0.051 Units on a scale | Standard Deviation 0.106 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 56 (Day 1) | 0.025 Units on a scale | Standard Deviation 0.1796 |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 57 (Day 1) | 0.031 Units on a scale | — |
| Sunitinib | Change From Baseline in European Quality of Life (EuroQol) 5-Dimension 5 Levels (EQ-5D-5L) Utility Score | Cycle 58 (Day 1) | 0.031 Units on a scale | — |
Secondary
Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit
Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured with the participant in the seated position after the participant had been sitting quietly for at least 5 minutes.
Time frame: Baseline (pre-dose on Day 1 of Cycle 1), Day 1 of Cycle 2, 3, 4, 5, 6, 7, EOT visit (maximum up to approximately 89 months) (each cycle=42 days)
Population: Safety analysis set included all participants who received at least one dose of study drug. Number Analyzed signifies number of participants evaluable for the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Avelumab + Axitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Change at Cycle 4, Day 1: Sitting DBP | 4.8 Millimeters of mercury | Standard Deviation 11.61 |
| Avelumab + Axitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Change at Cycle 5, Day 1: Sitting DBP | 4.5 Millimeters of mercury | Standard Deviation 11.17 |
| Avelumab + Axitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Change at Cycle 6, Day 1: Sitting DBP | 3.8 Millimeters of mercury | Standard Deviation 10.18 |
| Avelumab + Axitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Change at Cycle 7, Day 1: Sitting DBP | 3.8 Millimeters of mercury | Standard Deviation 11.04 |
| Avelumab + Axitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Change at End of Treatment: Sitting DBP | 1.5 Millimeters of mercury | Standard Deviation 12.7 |
| Avelumab + Axitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Baseline: Sitting SBP | 126.5 Millimeters of mercury | Standard Deviation 13.52 |
| Avelumab + Axitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Change at Cycle 2, Day 1: Sitting SBP | 4.7 Millimeters of mercury | Standard Deviation 16.08 |
| Avelumab + Axitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Change at Cycle 3, Day 1: Sitting SBP | 3.8 Millimeters of mercury | Standard Deviation 16.43 |
| Avelumab + Axitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Change at Cycle 4, Day 1: Sitting SBP | 3.0 Millimeters of mercury | Standard Deviation 15.95 |
| Avelumab + Axitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Change at Cycle 5, Day 1: Sitting SBP | 2.5 Millimeters of mercury | Standard Deviation 15.42 |
| Avelumab + Axitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Change at Cycle 6, Day 1: Sitting SBP | 1.6 Millimeters of mercury | Standard Deviation 15.39 |
| Avelumab + Axitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Change at Cycle 7, Day 1: Sitting SBP | 1.9 Millimeters of mercury | Standard Deviation 15.39 |
| Avelumab + Axitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Change at End of Treatment: Sitting SBP | 0.9 Millimeters of mercury | Standard Deviation 17.4 |
| Avelumab + Axitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Baseline: Sitting DBP | 75.7 Millimeters of mercury | Standard Deviation 9.32 |
| Avelumab + Axitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Change at Cycle 2, Day 1: Sitting DBP | 5.8 Millimeters of mercury | Standard Deviation 10.92 |
| Avelumab + Axitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Change at Cycle 3, Day 1: Sitting DBP | 4.9 Millimeters of mercury | Standard Deviation 10.98 |
| Sunitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Change at Cycle 3, Day 1: Sitting DBP | 0.0 Millimeters of mercury | Standard Deviation 9.64 |
| Sunitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Change at Cycle 4, Day 1: Sitting DBP | -1.9 Millimeters of mercury | Standard Deviation 9.3 |
| Sunitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Change at Cycle 4, Day 1: Sitting SBP | 0.1 Millimeters of mercury | Standard Deviation 13.01 |
| Sunitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Change at Cycle 5, Day 1: Sitting DBP | -1.9 Millimeters of mercury | Standard Deviation 9.71 |
| Sunitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Change at End of Treatment: Sitting SBP | 1.7 Millimeters of mercury | Standard Deviation 15.67 |
| Sunitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Change at Cycle 6, Day 1: Sitting DBP | -1.3 Millimeters of mercury | Standard Deviation 9.89 |
| Sunitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Change at Cycle 5, Day 1: Sitting SBP | -0.1 Millimeters of mercury | Standard Deviation 12.26 |
| Sunitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Change at Cycle 7, Day 1: Sitting DBP | -1.1 Millimeters of mercury | Standard Deviation 9.9 |
| Sunitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Change at Cycle 2, Day 1: Sitting DBP | -0.1 Millimeters of mercury | Standard Deviation 8.6 |
| Sunitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Change at End of Treatment: Sitting DBP | -0.9 Millimeters of mercury | Standard Deviation 10.92 |
| Sunitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Change at Cycle 6, Day 1: Sitting SBP | -0.1 Millimeters of mercury | Standard Deviation 12.97 |
| Sunitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Baseline: Sitting SBP | 126.3 Millimeters of mercury | Standard Deviation 12 |
| Sunitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Baseline: Sitting DBP | 75.9 Millimeters of mercury | Standard Deviation 9.41 |
| Sunitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Change at Cycle 2, Day 1: Sitting SBP | 0.8 Millimeters of mercury | Standard Deviation 12.49 |
| Sunitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Change at Cycle 7, Day 1: Sitting SBP | 0.4 Millimeters of mercury | Standard Deviation 13.56 |
| Sunitinib | Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit | Change at Cycle 3, Day 1: Sitting SBP | 1.2 Millimeters of mercury | Standard Deviation 12.81 |
Secondary
Change From Baseline in Vital Signs - Pulse Rate at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and EOT Visit
Pulse rate was measured with the participant in the seated position after the participant had been sitting quietly for at least 5 minutes.
Time frame: Baseline (pre-dose on Day 1 of Cycle 1), Day 1 of Cycle 2, 3, 4, 5, 6, 7, EOT visit (maximum up to approximately 89 months) (each cycle=42 days)
Population: Safety analysis set included all participants who received at least one dose of study drug. Here Number of Participants Analyzed signifies number of participants evaluable for this outcome measure. Number Analyzed signifies number of participants evaluable for the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Avelumab + Axitinib | Change From Baseline in Vital Signs - Pulse Rate at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and EOT Visit | Change at Cycle 5, Day 1 | -0.5 beats per minute | Standard Deviation 12 |
| Avelumab + Axitinib | Change From Baseline in Vital Signs - Pulse Rate at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and EOT Visit | Change at Cycle 3, Day 1 | 0.8 beats per minute | Standard Deviation 12.58 |
| Avelumab + Axitinib | Change From Baseline in Vital Signs - Pulse Rate at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and EOT Visit | Change at Cycle 6, Day 1 | -1.9 beats per minute | Standard Deviation 12.37 |
| Avelumab + Axitinib | Change From Baseline in Vital Signs - Pulse Rate at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and EOT Visit | Baseline | 75.4 beats per minute | Standard Deviation 12.49 |
| Avelumab + Axitinib | Change From Baseline in Vital Signs - Pulse Rate at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and EOT Visit | Change at Cycle 7, Day 1 | -1.9 beats per minute | Standard Deviation 11.69 |
| Avelumab + Axitinib | Change From Baseline in Vital Signs - Pulse Rate at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and EOT Visit | Change at Cycle 4, Day 1 | -0.6 beats per minute | Standard Deviation 12.79 |
| Avelumab + Axitinib | Change From Baseline in Vital Signs - Pulse Rate at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and EOT Visit | Change at End of Treatment | 2.9 beats per minute | Standard Deviation 15.29 |
| Avelumab + Axitinib | Change From Baseline in Vital Signs - Pulse Rate at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and EOT Visit | Change at Cycle 2, Day 1 | 0.4 beats per minute | Standard Deviation 12.77 |
| Sunitinib | Change From Baseline in Vital Signs - Pulse Rate at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and EOT Visit | Change at End of Treatment | 3.5 beats per minute | Standard Deviation 12.27 |
| Sunitinib | Change From Baseline in Vital Signs - Pulse Rate at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and EOT Visit | Baseline | 75.6 beats per minute | Standard Deviation 12.63 |
| Sunitinib | Change From Baseline in Vital Signs - Pulse Rate at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and EOT Visit | Change at Cycle 3, Day 1 | 3.1 beats per minute | Standard Deviation 11.34 |
| Sunitinib | Change From Baseline in Vital Signs - Pulse Rate at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and EOT Visit | Change at Cycle 4, Day 1 | 2.8 beats per minute | Standard Deviation 10.34 |
| Sunitinib | Change From Baseline in Vital Signs - Pulse Rate at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and EOT Visit | Change at Cycle 5, Day 1 | 2.5 beats per minute | Standard Deviation 10.82 |
| Sunitinib | Change From Baseline in Vital Signs - Pulse Rate at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and EOT Visit | Change at Cycle 6, Day 1 | 1.6 beats per minute | Standard Deviation 10.75 |
| Sunitinib | Change From Baseline in Vital Signs - Pulse Rate at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and EOT Visit | Change at Cycle 7, Day 1 | 2.1 beats per minute | Standard Deviation 10.13 |
| Sunitinib | Change From Baseline in Vital Signs - Pulse Rate at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and EOT Visit | Change at Cycle 2, Day 1 | 3.1 beats per minute | Standard Deviation 10.69 |
Secondary
Ctrough of Axitinib
Predose concentration during multiple dosing.
Time frame: Pre dose (0 hour) on day 15 and 29 of cycle 1 (each cycle= 6 weeks)
Population: Axitinib PK concentration analysis set: all participants who received at least one dose of study drug and have at least one post-dose concentration above lower limit of quantitation (LLQ) for axitinib. Here 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure. 'Number Analyzed' signifies number of participants evaluable for the specified rows. This outcome measure was not planned to be analyzed in ''Sunitinib'' reporting group.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Avelumab + Axitinib | Ctrough of Axitinib | Cycle1 (day 15) | 4.904 Nanograms per milliliter | Geometric Coefficient of Variation 172 |
| Avelumab + Axitinib | Ctrough of Axitinib | Cycle1 (day 29) | 6.272 Nanograms per milliliter | Geometric Coefficient of Variation 174 |
Secondary
DR as Assessed by Investigator in Participants Irrespective of PD-L1 Expression
Investigator assessed DR: time from first documentation of OR (confirmed CR or PR) to date of first documentation of objective tumor progression (PD) assessed by investigator or death due to any cause whichever occurred first. As per RECIST v1.1. CR: complete disappearance of all target and non-target lesions with the exception of nodal disease. All lymph nodes must decrease to normal size (short axis\<10 mm). All target lesions must be assessed. PR: \>=30% decrease under baseline of the sum of diameters of all target measurable lesions. All target lesions must be assessed. PD: at least a 20% increase in the sum of all the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to relative increase of 20%, sum must have also demonstrated an absolute \> of at least 5 mm. The appearance of one or more new lesions was also considered progression.
Time frame: From documentation of OR until date of first documentation of PD or death due to any cause, whichever occurred first (maximum up to approximately 89 months)
Population: FAS included all randomized participants. Here Number of Participants Analyzed signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Avelumab + Axitinib | DR as Assessed by Investigator in Participants Irrespective of PD-L1 Expression | 19.4 Months |
| Sunitinib | DR as Assessed by Investigator in Participants Irrespective of PD-L1 Expression | 14.5 Months |
Secondary
DR in PD-L1 Biomarker-Positive and PD-L1 Biomarker-Negative Subgroups
DR: time from first documentation of OR (confirmed CR or PR) to date of first documentation of PD or death due to any cause, whichever occurred first. As per RECIST version 1.1, CR: disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (target or non-target) must have reduction in short axis to \<10 mm. PR: at least 30%\< in sum of longest dimensions of target lesions taking as reference baseline sum longest dimensions. PD: defined as at least a 20% \> in sum of diameters of target lesions, taking as reference the smallest sum on study (this included baseline sum if that is smallest on study). In addition to relative increase of 20%, sum must have also demonstrated an absolute increase of at least 5 mm. Appearance of one or more new lesions was also considered progression.
Time frame: From documentation of OR until date of first documentation of PD or death due to any cause, whichever occurred first (maximum up to approximately 26 months)
Population: Biomarker positive/negative subset in FAS included participants who had at least one biomarker baseline assessment. Here Number of Participants Analyzed signifies participants evaluable for this outcome measure. Number Analyzed signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Avelumab + Axitinib | DR in PD-L1 Biomarker-Positive and PD-L1 Biomarker-Negative Subgroups | PD-L1 Positive Tumors | NA Months |
| Avelumab + Axitinib | DR in PD-L1 Biomarker-Positive and PD-L1 Biomarker-Negative Subgroups | PD-L1 Negative Tumors | NA Months |
| Sunitinib | DR in PD-L1 Biomarker-Positive and PD-L1 Biomarker-Negative Subgroups | PD-L1 Positive Tumors | NA Months |
| Sunitinib | DR in PD-L1 Biomarker-Positive and PD-L1 Biomarker-Negative Subgroups | PD-L1 Negative Tumors | NA Months |
Secondary
Duration of Response (DR) as Assessed by BICR in Participants Irrespective of PD-L1 Expression
BICR assessed DR: time from first documentation of OR (confirmed CR or PR) to date of first documentation of objective tumor progression assessed by BICR or death due to any cause whichever occurred first. As per RECIST v1.1. CR: complete disappearance of all target and non-target lesions with the exception of nodal disease. All lymph nodes must decrease to normal size (short axis\<10 mm). All target lesions must be assessed. PR: \>=30% decrease under baseline of the sum of diameters of all target measurable lesions. All target lesions must be assessed. PD: at least a 20% increase in the sum of all the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to relative increase of 20%, sum must have also demonstrated an absolute \> of at least 5 mm. The appearance of one or more new lesions was also considered progression.
Time frame: From documentation of OR until date of first documentation of PD or death due to any cause, whichever occurred first (maximum up to approximately 26 months)
Population: FAS included all randomized participants. Here Number of Participants Analyzed signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Avelumab + Axitinib | Duration of Response (DR) as Assessed by BICR in Participants Irrespective of PD-L1 Expression | NA Months |
| Sunitinib | Duration of Response (DR) as Assessed by BICR in Participants Irrespective of PD-L1 Expression | NA Months |
Secondary
Maximum Plasma Concentration (Cmax) of Axitinib
Time frame: 2 hours post-dose on Day 1, pre-dose and 2 hours post dose on Days 15 and 29 of Cycle 1
Population: Axitinib PK concentration analysis: all participants who received at least one dose of study drug and have at least one post-dose concentration above lower limit of quantitation (LLQ) for axitinib. Here Number of Participants Analyzed signifies participants evaluable for this outcome measure. Number Analyzed signifies number of participants evaluable for the specified rows. This outcome measure was not planned to be analyzed in ''Sunitinib'' reporting group.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Avelumab + Axitinib | Maximum Plasma Concentration (Cmax) of Axitinib | Cycle1 (day 1); Post Dose | 17.93 Nanogram per milliliter | Geometric Coefficient of Variation 182 |
| Avelumab + Axitinib | Maximum Plasma Concentration (Cmax) of Axitinib | Cycle1 (day 15); Pre-Dose | 4.904 Nanogram per milliliter | Geometric Coefficient of Variation 172 |
| Avelumab + Axitinib | Maximum Plasma Concentration (Cmax) of Axitinib | Cycle1 (day 15); Post Dose | 18.45 Nanogram per milliliter | Geometric Coefficient of Variation 157 |
| Avelumab + Axitinib | Maximum Plasma Concentration (Cmax) of Axitinib | Cycle1 (day 29); Pre-Dose | 6.272 Nanogram per milliliter | Geometric Coefficient of Variation 174 |
| Avelumab + Axitinib | Maximum Plasma Concentration (Cmax) of Axitinib | Cycle1 (day 29); Post Dose | 17.19 Nanogram per milliliter | Geometric Coefficient of Variation 174 |
Secondary
Number of Participants According to Grade Shift in Chemistry Parameters
Following chemistry parameters were assessed: alanine aminotransferase(ALT) increased, alkaline phosphatase(ALP) increased, aspartate aminotransferase(AST) increased, blood bilirubin increased, cholesterol high, creatinine phosphokinase(CPK) increased, creatinine increased, gamma glutamyl transferase(GGT) increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesmia, hypernatremia, hypertriglyceridemia, hypoalbuminemia, hypokalemia, hypomagnesemia, hyponatremia, lipase increased and serum amylase increased. Laboratory abnormality graded as per NCI CTCAE v4.03; G0=non-missing lab value that does not meet either of G1 through 4 criteria, G1=mild, G2=moderate, G3=severe, G4=life-threatening consequences and G5=death. Number of participants with a baseline grade of 0 to 4 which shifted to G3-4 post-baseline are reported. Only non-zero categories for any reporting arm are reported.
Time frame: From start of study treatment until 90 days after last dose of study treatment (maximum up to approximately 92 months)
Population: Safety analysis set included all participants who received at least one dose of study drug. Here Number of Participants Analyzed signifies number of participants evaluable for this outcome measure. Number Analyzed signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Blood bilirubin increased (Baseline G1 to post-baseline G3-4) | 2 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypercalcemia (Baseline G1 to post-baseline G3-4) | 1 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | ALT increased (Baseline G1 to post-baseline G3-4) | 3 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypercalcemia (Baseline G2 to post-baseline G3-4) | 1 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Cholesterol high (Baseline G0 to post-baseline G3-4) | 8 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypercalcemia (Baseline G3 to post-baseline G3-4) | 0 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypoalbunemia (Baseline G1 to post-baseline G3-4) | 1 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypercalcemia (Baseline G4 to post-baseline G3-4) | 0 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Cholesterol high (Baseline G1 to post-baseline G3-4) | 4 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hyperglycemia (Baseline G0 to post-baseline G3-4) | 37 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | ALP increased (Baseline G0 to post-baseline G3-4) | 9 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hyperglycemia (Baseline G1 to post-baseline G3-4) | 4 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Cholesterol high (Baseline G2 to post-baseline G3-4) | 0 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hyperglycemia (Baseline G2 to post-baseline G3-4) | 5 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypertriglyceridemia (Baseline G1 to post-baseline G3-4) | 31 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hyperglycemia (Baseline G3 to post-baseline G3-4) | 6 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | CPK increased (Baseline G0 to post-baseline G3-4) | 7 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hyperkalemia (Baseline G0 to post-baseline G3-4) | 19 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | ALP increased (Baseline G1 to post-baseline G3-4) | 5 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hyperkalemia (Baseline G1 to post-baseline G3-4) | 1 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | CPK increased (Baseline G2 to post-baseline G3-4) | 0 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hyperkalemia (Baseline G2 to post-baseline G3-4) | 3 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | ALP increased (Baseline G2 to post-baseline G3-4) | 1 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hyperkalemia (Baseline G3 to post-baseline G3-4) | 1 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | CPK increased (Baseline G1 to post-baseline G3-4) | 0 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hyperkalemia (Baseline G4 to post-baseline G3-4) | 0 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypoalbunemia (Baseline G2 to post-baseline G3-4) | 2 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypermagnesemia (Baseline G0 to post-baseline G3-4) | 13 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypertriglyceridemia (Baseline G4 to post-baseline G3-4) | 0 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypermagnesemia (Baseline G1 to post-baseline G3-4) | 1 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | CPK increased (Baseline G3 to post-baseline G3-4) | 1 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypernatremia (Baseline G0 to post-baseline G3-4) | 7 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | ALP increased (Baseline G3 to post-baseline G3-4) | 4 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypertriglyceridemia (Baseline G0 to post-baseline G3-4) | 18 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypocalcemia (Baseline G1 to post-baseline G3-4) | 0 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Creatinine increased (Baseline G0 to post-baseline G3-4) | 7 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypocalcemia (Baseline G2 to post-baseline G3-4) | 1 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypertriglyceridemia (Baseline G3 to post-baseline G3-4) | 4 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypoglycemia (Baseline G0 to post-baseline G3-4) | 2 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Creatinine increased (Baseline G1 to post-baseline G3-4) | 4 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypokalemia (Baseline G0 to post-baseline G3-4) | 17 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | AST increased (Baseline G0 to post-baseline G3-4) | 26 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypokalemia (Baseline G2 to post-baseline G3-4) | 2 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Creatinine increased (Baseline G2 to post-baseline G3-4) | 0 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypomagnesemia (Baseline G0 to post-baseline G3-4) | 3 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypoalbunemia (Baseline G0 to post-baseline G3-4) | 3 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypomagnesemia (Baseline G1 to post-baseline G3-4) | 2 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Creatinine increased (Baseline G3 to post-baseline G3-4) | 0 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypomagnesemia (Baseline G2 to post-baseline G3-4) | 1 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | AST increased (Baseline G1 to post-baseline G3-4) | 6 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hyponatremia (Baseline G0 to post-baseline G3-4) | 42 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | GGT increased (Baseline G0 to post-baseline G3-4) | 15 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hyponatremia (Baseline G1 to post-baseline G3-4) | 19 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypocalcemia (Baseline G0 to post-baseline G3-4) | 4 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hyponatremia (Baseline G3 to post-baseline G3-4) | 1 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | GGT increased (Baseline G1 to post-baseline G3-4) | 20 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Lipase increased (Baseline G0 to post-baseline G3-4) | 63 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | AST increased (Baseline G3 to post-baseline G3-4) | 1 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Lipase increased (Baseline G1 to post-baseline G3-4) | 19 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | GGT increased (Baseline G2 to post-baseline G3-4) | 12 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Lipase increased (Baseline G2 to post-baseline G3-4) | 7 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | ALT increased (Baseline G0 to post-baseline G3-4) | 42 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Lipase increased (Baseline G3 to post-baseline G3-4) | 2 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | GGT increased (Baseline G3 to post-baseline G3-4) | 7 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Lipase increased (Baseline G4 to post-baseline G3-4) | 1 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Blood bilirubin increased (Baseline G0 to post-baseline G3-4) | 3 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Serum amylase increased (Baseline G0 to post-baseline G3-4) | 21 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | GGT increased (Baseline G4 to post-baseline G3-4) | 0 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Serum amylase increased (Baseline G1 to post-baseline G3-4) | 12 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypertriglyceridemia (Baseline G2 to post-baseline G3-4) | 15 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Serum amylase increased (Baseline G2 to post-baseline G3-4) | 4 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypercalcemia (Baseline G0 to post-baseline G3-4) | 4 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Serum amylase increased (Baseline G3 to post-baseline G3-4) | 1 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypoalbunemia (Baseline G3 to post-baseline G3-4) | 1 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Serum amylase increased (Baseline G3 to post-baseline G3-4) | 3 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypocalcemia (Baseline G0 to post-baseline G3-4) | 4 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | ALP increased (Baseline G1 to post-baseline G3-4) | 6 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypermagnesemia (Baseline G0 to post-baseline G3-4) | 20 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypertriglyceridemia (Baseline G1 to post-baseline G3-4) | 23 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypertriglyceridemia (Baseline G2 to post-baseline G3-4) | 6 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypertriglyceridemia (Baseline G3 to post-baseline G3-4) | 5 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypertriglyceridemia (Baseline G0 to post-baseline G3-4) | 3 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypertriglyceridemia (Baseline G4 to post-baseline G3-4) | 1 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypoalbunemia (Baseline G0 to post-baseline G3-4) | 6 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypoalbunemia (Baseline G1 to post-baseline G3-4) | 1 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypoalbunemia (Baseline G2 to post-baseline G3-4) | 2 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypoalbunemia (Baseline G3 to post-baseline G3-4) | 2 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | ALT increased (Baseline G0 to post-baseline G3-4) | 19 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | ALT increased (Baseline G1 to post-baseline G3-4) | 0 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | ALP increased (Baseline G0 to post-baseline G3-4) | 0 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | ALP increased (Baseline G2 to post-baseline G3-4) | 3 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | ALP increased (Baseline G3 to post-baseline G3-4) | 1 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | AST increased (Baseline G0 to post-baseline G3-4) | 16 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | AST increased (Baseline G1 to post-baseline G3-4) | 4 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | AST increased (Baseline G3 to post-baseline G3-4) | 0 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Blood bilirubin increased (Baseline G0 to post-baseline G3-4) | 6 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Blood bilirubin increased (Baseline G1 to post-baseline G3-4) | 0 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Cholesterol high (Baseline G0 to post-baseline G3-4) | 3 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Cholesterol high (Baseline G1 to post-baseline G3-4) | 3 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Cholesterol high (Baseline G2 to post-baseline G3-4) | 1 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | CPK increased (Baseline G0 to post-baseline G3-4) | 7 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | CPK increased (Baseline G2 to post-baseline G3-4) | 1 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | CPK increased (Baseline G1 to post-baseline G3-4) | 2 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | CPK increased (Baseline G3 to post-baseline G3-4) | 0 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Creatinine increased (Baseline G0 to post-baseline G3-4) | 2 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Creatinine increased (Baseline G1 to post-baseline G3-4) | 5 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Creatinine increased (Baseline G2 to post-baseline G3-4) | 1 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Creatinine increased (Baseline G3 to post-baseline G3-4) | 1 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | GGT increased (Baseline G0 to post-baseline G3-4) | 16 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | GGT increased (Baseline G1 to post-baseline G3-4) | 7 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | GGT increased (Baseline G2 to post-baseline G3-4) | 4 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | GGT increased (Baseline G3 to post-baseline G3-4) | 2 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | GGT increased (Baseline G4 to post-baseline G3-4) | 1 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypercalcemia (Baseline G0 to post-baseline G3-4) | 4 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypercalcemia (Baseline G1 to post-baseline G3-4) | 2 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypercalcemia (Baseline G2 to post-baseline G3-4) | 1 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypercalcemia (Baseline G3 to post-baseline G3-4) | 2 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypercalcemia (Baseline G4 to post-baseline G3-4) | 1 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hyperglycemia (Baseline G0 to post-baseline G3-4) | 20 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hyperglycemia (Baseline G1 to post-baseline G3-4) | 3 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hyperglycemia (Baseline G2 to post-baseline G3-4) | 3 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hyperglycemia (Baseline G3 to post-baseline G3-4) | 4 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hyperkalemia (Baseline G0 to post-baseline G3-4) | 16 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hyperkalemia (Baseline G1 to post-baseline G3-4) | 5 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hyperkalemia (Baseline G2 to post-baseline G3-4) | 3 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hyperkalemia (Baseline G3 to post-baseline G3-4) | 0 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hyperkalemia (Baseline G4 to post-baseline G3-4) | 1 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypermagnesemia (Baseline G1 to post-baseline G3-4) | 2 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypernatremia (Baseline G0 to post-baseline G3-4) | 2 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypocalcemia (Baseline G1 to post-baseline G3-4) | 1 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypocalcemia (Baseline G2 to post-baseline G3-4) | 0 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypoglycemia (Baseline G0 to post-baseline G3-4) | 1 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypokalemia (Baseline G0 to post-baseline G3-4) | 15 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypokalemia (Baseline G2 to post-baseline G3-4) | 1 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypomagnesemia (Baseline G0 to post-baseline G3-4) | 1 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypomagnesemia (Baseline G1 to post-baseline G3-4) | 1 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hypomagnesemia (Baseline G2 to post-baseline G3-4) | 0 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hyponatremia (Baseline G0 to post-baseline G3-4) | 35 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hyponatremia (Baseline G1 to post-baseline G3-4) | 14 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Hyponatremia (Baseline G3 to post-baseline G3-4) | 2 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Lipase increased (Baseline G0 to post-baseline G3-4) | 27 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Lipase increased (Baseline G1 to post-baseline G3-4) | 8 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Lipase increased (Baseline G2 to post-baseline G3-4) | 3 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Lipase increased (Baseline G3 to post-baseline G3-4) | 7 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Lipase increased (Baseline G4 to post-baseline G3-4) | 0 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Serum amylase increased (Baseline G0 to post-baseline G3-4) | 4 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Serum amylase increased (Baseline G1 to post-baseline G3-4) | 4 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Chemistry Parameters | Serum amylase increased (Baseline G2 to post-baseline G3-4) | 4 Participants |
Secondary
Number of Participants According to Grade Shift in Hematology Parameters
Following hematology parameters were assessed: hemoglobin decreased (anemia), hemoglobin increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased and white blood cell (WBC) decreased. Laboratory abnormalities were graded as per NCI- CTCAE v 4.03 where, grade(G) 0= non-missing lab value that does not meet either of G1 through 4 criteria, G1=mild, G2=moderate, G3=severe, G4=life-threatening consequences and G5=death. Baseline was defined as last assessment prior to first dose of study treatment. Number of participants with a baseline grade of 0 to 4 which shifted to G3-4 post-baseline are reported in this outcome measure. Only non-zero categories for any reporting arm are reported.
Time frame: From start of study treatment until 90 days after last dose of study treatment (maximum up to approximately 92 months)
Population: Safety analysis set included all participants who received at least one dose of study drug. Here Number of Participants Analyzed signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Hematology Parameters | Anemia (Baseline G0 to post-baseline G3-4) | 3 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Hematology Parameters | Anemia (Baseline G1 to post-baseline G3-4) | 6 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Hematology Parameters | Anemia (Baseline G2 to post-baseline G3-4) | 4 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Hematology Parameters | Anemia (Baseline G3 to post-baseline G3-4) | 0 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Hematology Parameters | Lymphocytes count decreased (Baseline G0 to post-baseline G3-4) | 21 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Hematology Parameters | Lymphocytes count decreased (Baseline G1 to post-baseline G3-4) | 11 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Hematology Parameters | Lymphocytes count decreased (Baseline G2 to post-baseline G3-4) | 7 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Hematology Parameters | Lymphocytes count decreased (Baseline G3 to post-baseline G3-4) | 2 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Hematology Parameters | Neutrophils count decreased (Baseline G0 to post-baseline G3-4) | 7 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Hematology Parameters | Neutrophils count decreased (Baseline G1 to post-baseline G3-4) | 0 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Hematology Parameters | Neutrophils count decreased (Baseline G2 to post-baseline G3-4) | 0 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Hematology Parameters | Platelets count decreased (Baseline G0 to post-baseline G3-4) | 3 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Hematology Parameters | Platelets count decreased (Baseline G1 to post-baseline G3-4) | 1 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Hematology Parameters | WBC decreased (Baseline G0 to post-baseline G3-4) | 1 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Hematology Parameters | WBC decreased (Baseline G1 to post-baseline G3-4) | 0 Participants |
| Avelumab + Axitinib | Number of Participants According to Grade Shift in Hematology Parameters | WBC decreased (Baseline G2 to post-baseline G3-4) | 0 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Hematology Parameters | WBC decreased (Baseline G2 to post-baseline G3-4) | 2 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Hematology Parameters | Anemia (Baseline G0 to post-baseline G3-4) | 9 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Hematology Parameters | Neutrophils count decreased (Baseline G0 to post-baseline G3-4) | 108 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Hematology Parameters | Anemia (Baseline G1 to post-baseline G3-4) | 21 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Hematology Parameters | Platelets count decreased (Baseline G1 to post-baseline G3-4) | 6 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Hematology Parameters | Anemia (Baseline G2 to post-baseline G3-4) | 14 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Hematology Parameters | Neutrophils count decreased (Baseline G1 to post-baseline G3-4) | 2 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Hematology Parameters | Anemia (Baseline G3 to post-baseline G3-4) | 2 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Hematology Parameters | WBC decreased (Baseline G1 to post-baseline G3-4) | 7 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Hematology Parameters | Lymphocytes count decreased (Baseline G0 to post-baseline G3-4) | 53 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Hematology Parameters | Neutrophils count decreased (Baseline G2 to post-baseline G3-4) | 1 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Hematology Parameters | Lymphocytes count decreased (Baseline G1 to post-baseline G3-4) | 18 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Hematology Parameters | WBC decreased (Baseline G0 to post-baseline G3-4) | 35 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Hematology Parameters | Lymphocytes count decreased (Baseline G2 to post-baseline G3-4) | 15 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Hematology Parameters | Platelets count decreased (Baseline G0 to post-baseline G3-4) | 61 Participants |
| Sunitinib | Number of Participants According to Grade Shift in Hematology Parameters | Lymphocytes count decreased (Baseline G3 to post-baseline G3-4) | 6 Participants |
Secondary
Number of Participants Who Discontinued Treatment Due to Toxicity
Number of participants who discontinued treatment due to toxicity are reported in this outcome measure.
Time frame: From first dose of study treatment until discontinuation of study treatment (maximum up to approximately 89 months)
Population: Safety analysis set included all participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Avelumab + Axitinib | Number of Participants Who Discontinued Treatment Due to Toxicity | 136 Participants |
| Sunitinib | Number of Participants Who Discontinued Treatment Due to Toxicity | 65 Participants |
Secondary
Number of Participants With Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb) of Avelumab When Used in Combination With Axitinib
Time frame: From start of treatment until 30 days after the end of avelumab treatment (maximum up to approximately 89 months)
Population: Immunogenicity analysis set included all participants who received at least one dose of study drug and who had at least one ADA/nAb sample collected for avelumab in Avelumab + Axitinib arm. Here Number of Participants Analyzed signifies participants evaluable for this outcome measure. This outcome measure was not planned to be analyzed for ''Sunitinib'' reporting group.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Avelumab + Axitinib | Number of Participants With Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb) of Avelumab When Used in Combination With Axitinib | ADA Positive | 77 Participants |
| Avelumab + Axitinib | Number of Participants With Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb) of Avelumab When Used in Combination With Axitinib | nAb Positive | 51 Participants |
Secondary
Number of Participants With Positive PD-L1 Biomarker Expression in Pre-treatment Tumor Tissue
Tumor biospecimens from pre-treatment tissue samples were analyzed by immunohistochemistry for PD-L1 biomarker expression. Number of participants with positive PD-L1 biomarker expression are reported in this outcome measure.
Time frame: At screening
Population: Biomarker analysis set for biomarkers that are measured only at screening, included all participants who received at least one dose of study drug and who had at least one screening biomarker assessment. Here Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Avelumab + Axitinib | Number of Participants With Positive PD-L1 Biomarker Expression in Pre-treatment Tumor Tissue | 266 Participants |
| Sunitinib | Number of Participants With Positive PD-L1 Biomarker Expression in Pre-treatment Tumor Tissue | 288 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (AEs) Graded Based on National Cancer Institute -Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (V) 4.03
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were those events with onset dates occurring during the on-treatment period for the first time, or if the worsening of an event was during the on-treatment period (time from the first dose of study treatment through 90 days after last dose of study treatment or start day of new anti-cancer drug therapy-1 day). As per NCI-CTCAE v4.03, grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening consequences and grade 5=death.
Time frame: From start of study treatment until 90 days after last dose of study treatment (maximum up to approximately 92 months)
Population: Safety analysis set included all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Avelumab + Axitinib | Number of Participants With Treatment-Emergent Adverse Events (AEs) Graded Based on National Cancer Institute -Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (V) 4.03 | Grade 2 | 64 Participants |
| Avelumab + Axitinib | Number of Participants With Treatment-Emergent Adverse Events (AEs) Graded Based on National Cancer Institute -Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (V) 4.03 | Grade 4 | 64 Participants |
| Avelumab + Axitinib | Number of Participants With Treatment-Emergent Adverse Events (AEs) Graded Based on National Cancer Institute -Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (V) 4.03 | Grade 3 | 271 Participants |
| Avelumab + Axitinib | Number of Participants With Treatment-Emergent Adverse Events (AEs) Graded Based on National Cancer Institute -Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (V) 4.03 | Grade 5 | 30 Participants |
| Avelumab + Axitinib | Number of Participants With Treatment-Emergent Adverse Events (AEs) Graded Based on National Cancer Institute -Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (V) 4.03 | Grade 1 | 5 Participants |
| Sunitinib | Number of Participants With Treatment-Emergent Adverse Events (AEs) Graded Based on National Cancer Institute -Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (V) 4.03 | Grade 5 | 24 Participants |
| Sunitinib | Number of Participants With Treatment-Emergent Adverse Events (AEs) Graded Based on National Cancer Institute -Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (V) 4.03 | Grade 1 | 17 Participants |
| Sunitinib | Number of Participants With Treatment-Emergent Adverse Events (AEs) Graded Based on National Cancer Institute -Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (V) 4.03 | Grade 2 | 73 Participants |
| Sunitinib | Number of Participants With Treatment-Emergent Adverse Events (AEs) Graded Based on National Cancer Institute -Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (V) 4.03 | Grade 3 | 268 Participants |
| Sunitinib | Number of Participants With Treatment-Emergent Adverse Events (AEs) Graded Based on National Cancer Institute -Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (V) 4.03 | Grade 4 | 54 Participants |
Secondary
OS in Participants Irrespective of PD-L1 Expression
OS was defined as the time (in months) from the date of randomization 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.
Time frame: From the date of randomization to the date of death due to any cause or censoring date, whichever occurred first (maximum up to approximately 89 months)
Population: FAS included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Avelumab + Axitinib | OS in Participants Irrespective of PD-L1 Expression | 44.8 Months |
| Sunitinib | OS in Participants Irrespective of PD-L1 Expression | 38.9 Months |
p-value: 0.133895% CI: [0.749, 1.039]Log Rank
Secondary
Percentage of Participants With DC as Assessed by Investigator Irrespective of PD-L1 Expression
DC was defined as a best overall response of CR, PR, non-CR/non-PD or SD according to RECIST v1.1 as assessed by investigator. CR was defined as complete disappearance of all target and non-target lesions, with the exception of nodal disease and sustained for at least 4 weeks. All lymph nodes must decrease to normal size (short axis\<10mm). PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions. Non-CR/Non-PD was defined as persistence of any non-target lesions and/or tumor marker level above the normal limits. SD was defined as not to qualify for CR, PR or PD for target lesions and followed PR only if the sum increased by less than 20% from the nadir (smallest sum of diameters consider baseline and all assessments prior to the time point under evaluation), but enough that a previously documented 30% decrease no longer holds.
Time frame: From date of randomization until PD (maximum up to approximately 89 months)
Population: FAS included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Avelumab + Axitinib | Percentage of Participants With DC as Assessed by Investigator Irrespective of PD-L1 Expression | 85.1 Percentage of participants |
| Sunitinib | Percentage of Participants With DC as Assessed by Investigator Irrespective of PD-L1 Expression | 76.4 Percentage of participants |
Secondary
Percentage of Participants With DC in Biomarker-Positive Subgroup
DC was defined as a best overall response of CR, PR, or stable disease (SD) according to the RECIST v.1.1 recorded from randomization until disease progression or death due to any cause, whichever occurred first. CR was defined as complete disappearance of all target and non-target lesions with the exception of nodal disease. All lymph nodes must decrease to normal size (short axis\<10 mm). All target lesions must be assessed. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. All target lesions must be assessed. SD was defined as PR that the sum increases by less than 20% from the nadir, (smallest sum of diameters consider baseline and all assessments prior to the time point under evaluation), but enough that a previously documented 30% decrease no longer holds.
Time frame: From date of randomization until PD or death, whichever occurred first (maximum up to approximately 26 months)
Population: Biomarker positive subset in FAS included participants who had at least one biomarker baseline assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Avelumab + Axitinib | Percentage of Participants With DC in Biomarker-Positive Subgroup | 84.4 Percentage of participants |
| Sunitinib | Percentage of Participants With DC in Biomarker-Positive Subgroup | 71.0 Percentage of participants |
Secondary
Percentage of Participants With Disease Control (DC) as Assessed by BICR Irrespective of PD-L1 Expression
DC was defined as a best overall response of CR, PR, non-CR/non-PD or stable disease (SD) according to RECIST v1.1 as assessed by BICR. CR was defined as complete disappearance of all target and non-target lesions, with the exception of nodal disease and sustained for at least 4 weeks. All lymph nodes must decrease to normal size (short axis\<10mm). PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions. Non-CR/Non-PD was defined as persistence of any non-target lesions and/or tumor marker level above the normal limits. SD was defined as not to qualify for CR, PR or PD for target lesions and followed PR only if the sum increased by less than 20% from the nadir (smallest sum of diameters consider baseline and all assessments prior to the time point under evaluation), but enough that a previously documented 30% decrease no longer holds.
Time frame: From date of randomization until PD (maximum up to approximately 26 months)
Population: FAS included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Avelumab + Axitinib | Percentage of Participants With Disease Control (DC) as Assessed by BICR Irrespective of PD-L1 Expression | 82.8 Percentage of participants |
| Sunitinib | Percentage of Participants With Disease Control (DC) as Assessed by BICR Irrespective of PD-L1 Expression | 73.4 Percentage of participants |
Secondary
Percentage of Participants With Objective Response (OR) as Assessed by BICR Irrespective of PD-L1 Expression
OR was defined as best overall response of complete response (CR) or partial response (PR) according to RECIST v1.1 as assessed by BICR recorded from date of randomization until disease progression. CR was defined as complete disappearance of all target and non-target lesions with the exception of nodal disease. All lymph nodes must decrease to normal size (short axis\<10 mm). All target lesions must be assessed. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. All target lesions must be assessed. 95% CI was based on Clopper-Pearson method.
Time frame: From date of randomization until PD (maximum up to approximately 26 months)
Population: FAS included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Avelumab + Axitinib | Percentage of Participants With Objective Response (OR) as Assessed by BICR Irrespective of PD-L1 Expression | 51.4 Percentage of participants |
| Sunitinib | Percentage of Participants With Objective Response (OR) as Assessed by BICR Irrespective of PD-L1 Expression | 25.7 Percentage of participants |
Secondary
Percentage of Participants With OR as Assessed by Investigator Irrespective of PD-L1 Expression
OR was defined as best overall response of CR or PR according to RECIST v1.1 as assessed by investigator recorded from date of randomization until disease progression. CR was defined as complete disappearance of all target and non-target lesions with the exception of nodal disease. All lymph nodes must decrease to normal size (short axis\<10 mm). All target lesions must be assessed. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. All target lesions must be assessed. 95% CI was based on Clopper-Pearson method.
Time frame: From date of randomization until PD (maximum up to approximately 89 months)
Population: FAS included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Avelumab + Axitinib | Percentage of Participants With OR as Assessed by Investigator Irrespective of PD-L1 Expression | 59.7 Percentage of participants |
| Sunitinib | Percentage of Participants With OR as Assessed by Investigator Irrespective of PD-L1 Expression | 32.0 Percentage of participants |
Secondary
Percentage of Participants With OR in PD-L1 Biomarker-Positive and PD-L1 Biomarker-Negative Subgroups
OR was defined as best overall response of CR or PR according to RECIST v1.1 as assessed by BICR recorded from date of randomization until disease progression. CR was defined as complete disappearance of all target and non-target lesions with the exception of nodal disease. All lymph nodes must decrease to normal size (short axis\<10 mm). All target lesions must be assessed. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. All target lesions must be assessed.
Time frame: From date of randomization until PD (maximum up to approximately 26 months)
Population: Biomarker positive/negative subset in FAS included participants who had at least one biomarker baseline assessment. Here Number of Participants Analyzed signifies participants evaluable for this outcome measure. Number Analyzed signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Avelumab + Axitinib | Percentage of Participants With OR in PD-L1 Biomarker-Positive and PD-L1 Biomarker-Negative Subgroups | PD-L1 Positive Tumors | 55.2 Percentage of participants |
| Avelumab + Axitinib | Percentage of Participants With OR in PD-L1 Biomarker-Positive and PD-L1 Biomarker-Negative Subgroups | PD-L1 Negative Tumors | 47.0 Percentage of participants |
| Sunitinib | Percentage of Participants With OR in PD-L1 Biomarker-Positive and PD-L1 Biomarker-Negative Subgroups | PD-L1 Positive Tumors | 25.5 Percentage of participants |
| Sunitinib | Percentage of Participants With OR in PD-L1 Biomarker-Positive and PD-L1 Biomarker-Negative Subgroups | PD-L1 Negative Tumors | 28.3 Percentage of participants |
Secondary
PFS as Assessed by BICR in Participants Irrespective of PD-L1 Expression
PFS: time from the date of randomization to the date of the first documentation of PD or death due to any cause, whichever occurred first as assessed by BICR. PFS data was censored on date of last adequate tumor assessment for participants who did not have an event (PD or death), who started new anti-cancer therapy prior to an event or for participants with an event after 2 or more missing tumor assessments. PD was defined as at least a 20% increase in the sum of all the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to relative increase of 20 %, sum must have also demonstrated an absolute \> of at least 5 mm. The appearance of one or more new lesions was also considered progression.
Time frame: From date of randomization to the first documentation of PD or death due to any cause or censoring date, whichever occurred first (maximum up to approximately 26 months)
Population: FAS included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Avelumab + Axitinib | PFS as Assessed by BICR in Participants Irrespective of PD-L1 Expression | 13.8 Months |
| Sunitinib | PFS as Assessed by BICR in Participants Irrespective of PD-L1 Expression | 8.4 Months |
p-value: 0.000295% CI: [0.563, 0.84]Log Rank
Secondary
PFS as Assessed by Investigator in Participants Irrespective of PD-L1 Expression
Investigator assessed PFS: time from the date of randomization to the date of the first documentation of PD according to RECIST v1.1 or death due to any cause, whichever occurred first. PFS data was censored on date of last adequate tumor assessment for participants who did not have an event (PD or death), who started new anti-cancer therapy prior to an event or for participants with an event after 2 or more missing tumor assessments. PD was defined as at least a 20% increase in the sum of all the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to relative increase of 20 %, sum must have also demonstrated an absolute \> of at least 5 mm. The appearance of one or more new lesions was also considered progression.
Time frame: From date of randomization until PD, whichever occurred first (maximum up to approximately 89 months)
Population: FAS included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Avelumab + Axitinib | PFS as Assessed by Investigator in Participants Irrespective of PD-L1 Expression | 13.9 Months |
| Sunitinib | PFS as Assessed by Investigator in Participants Irrespective of PD-L1 Expression | 8.5 Months |
p-value: <0.000195% CI: [0.565, 0.768]Log Rank
Secondary
PFS in PD-L1 Biomarker-Positive and PD-L1 Biomarker-Negative Subgroups
PFS: time from the date of randomization to the date of the first documentation of PD according to RECIST v1.1 or death due to any cause, whichever occurred first. PFS data was censored on date of last adequate tumor assessment for participants who did not have an event (PD or death), who started new anti-cancer therapy prior to an event or for participants with an event after 2 or more missing tumor assessments. PD was defined as at least a 20% increase in the sum of all the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to relative increase of 20 %, sum must have also demonstrated an absolute \> of at least 5 mm. The appearance of one or more new lesions was also considered progression.
Time frame: From date of randomization to the first documentation of PD or death due to any cause or censoring date, whichever occurred first (maximum up to approximately 26 months)
Population: Biomarker positive/negative subset in FAS included participants who had at least one biomarker baseline assessment. Here Number of Participants Analyzed signifies participants evaluable for this outcome measure. Number Analyzed signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Avelumab + Axitinib | PFS in PD-L1 Biomarker-Positive and PD-L1 Biomarker-Negative Subgroups | PD-L1 Positive Tumors | 13.8 Months |
| Avelumab + Axitinib | PFS in PD-L1 Biomarker-Positive and PD-L1 Biomarker-Negative Subgroups | PD-L1 Negative Tumors | 16.1 Months |
| Sunitinib | PFS in PD-L1 Biomarker-Positive and PD-L1 Biomarker-Negative Subgroups | PD-L1 Positive Tumors | 7.2 Months |
| Sunitinib | PFS in PD-L1 Biomarker-Positive and PD-L1 Biomarker-Negative Subgroups | PD-L1 Negative Tumors | 11.1 Months |
Secondary
Progression-Free Survival on Next-line Therapy (PFS2) in Participants Irrespective of PD-L1 Expression
PFS2 is defined as the time (in months) from randomization to discontinuation of next-line treatment after first objective disease progression by investigator assessment, second objective disease progression by investigator assessment after initiation of next-line treatment, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of all the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to relative increase of 20 %, sum must have also demonstrated an absolute \> of at least 5 mm. The appearance of one or more new lesions was also considered progression.
Time frame: From date of randomization until PD or death, whichever occurred first (maximum up to approximately 89 months)
Population: FAS included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Avelumab + Axitinib | Progression-Free Survival on Next-line Therapy (PFS2) in Participants Irrespective of PD-L1 Expression | 30.4 Months |
| Sunitinib | Progression-Free Survival on Next-line Therapy (PFS2) in Participants Irrespective of PD-L1 Expression | 19.4 Months |
95% CI: [0.551, 0.754]
Secondary
Time to Symptom Deterioration (TTD) for Functional Assessment of Cancer Therapy (FACT)-Kidney Symptom Index - Disease Related Symptoms (FKSI-DRS)
TTD was defined as the time from date of randomization to the first time the participant's score showed a 3-point or greater decrease in FKSI-DRS. FKSI was used to assess symptoms and quality of life (QoL) for those diagnosed with advanced kidney cancer and it consisted of 19 questions. A 9-item subscale of the FKSI known as FKSI-Disease Related Symptoms subscale (FKSI-DRS). This subscale included 9 items: lack of energy, pain, losing weight, bone pain, fatigue, shortness of breath, coughing, bothered by fevers, and hematuria. Each of the 9 items was answered on a 5-point Likert-type scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI-DRS score = sum of the 9 item scores; total range: 0 - 36; 0 (no symptoms) to 36 (very much); higher score indicated greater presence of symptoms.
Time frame: Date of randomization to the first time the participant's score showed a 3-point or greater decrease in FKSI-DRS (maximum up to approximately 26 months)
Population: FAS included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Avelumab + Axitinib | Time to Symptom Deterioration (TTD) for Functional Assessment of Cancer Therapy (FACT)-Kidney Symptom Index - Disease Related Symptoms (FKSI-DRS) | 4.2 Months |
| Sunitinib | Time to Symptom Deterioration (TTD) for Functional Assessment of Cancer Therapy (FACT)-Kidney Symptom Index - Disease Related Symptoms (FKSI-DRS) | 6.3 Months |
Secondary
Time to Treatment Discontinuation/Failure Due to Toxicity
Time to treatment discontinuation/ failure due to toxicity was defined as the time from first dose of study treatment to discontinuation of study treatment due to an adverse event or death due to study treatment toxicity.
Time frame: From first dose of study treatment until discontinuation of study treatment (maximum up to approximately 89 months)
Population: Safety analysis set included all participants who received at least one dose of study drug. Here Number of Participants Analyzed signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Avelumab + Axitinib | Time to Treatment Discontinuation/Failure Due to Toxicity | 13.5 Months | Standard Deviation 17.41 |
| Sunitinib | Time to Treatment Discontinuation/Failure Due to Toxicity | 10.5 Months | Standard Deviation 12.82 |
Secondary
Time to Tumor Response (TTR) as Assessed by BICR in Participants Irrespective of PD-L1 Expression
TTR was defined as the time from randomization to the first documentation of objective tumor response according to RECIST v1.1 as assessed by BICR (CR or PR) which is subsequently confirmed. CR was defined as complete disappearance of all target and non-target lesions with the exception of nodal disease. All lymph nodes must decrease to normal size (short axis\<10 mm). All target lesions must be assessed. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. All target lesions must be assessed.
Time frame: From the date of randomization to the first documentation of objective response (CR or PR) (maximum up to approximately 26 months)
Population: FAS included all randomized participants. Here Number of Participants Analyzed signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Avelumab + Axitinib | Time to Tumor Response (TTR) as Assessed by BICR in Participants Irrespective of PD-L1 Expression | 2.6 Months |
| Sunitinib | Time to Tumor Response (TTR) as Assessed by BICR in Participants Irrespective of PD-L1 Expression | 3.2 Months |
Secondary
Trough Plasma Concentration (Ctrough) of Avelumab
Predose concentration during multiple dosing.
Time frame: Pre dose (0 hour) on Day 1, 15 and 29 of Cycle 1, Day 1 and 29 of Cycles 2, 3, 4 and Day 1 of Cycle 6
Population: Avelumab PK concentration analysis set: all participants who had at least one post-dose concentration above lower limit of quantitation (LLQ) for avelumab. Here Number of Participants Analyzed signifies participants evaluable for this outcome measure. Number Analyzed signifies number of participants evaluable for the specified rows. This outcome measure was not planned to be analyzed in ''Sunitinib'' reporting group.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Avelumab + Axitinib | Trough Plasma Concentration (Ctrough) of Avelumab | Cycle 1 (day 1) | 4.218 Micrograms per milliliter | Geometric Coefficient of Variation 1232 |
| Avelumab + Axitinib | Trough Plasma Concentration (Ctrough) of Avelumab | Cycle 1 (day 15) | 18.69 Micrograms per milliliter | Geometric Coefficient of Variation 102 |
| Avelumab + Axitinib | Trough Plasma Concentration (Ctrough) of Avelumab | Cycle 1 (day 29) | 21.99 Micrograms per milliliter | Geometric Coefficient of Variation 96 |
| Avelumab + Axitinib | Trough Plasma Concentration (Ctrough) of Avelumab | Cycle 2 (day 1) | 24.87 Micrograms per milliliter | Geometric Coefficient of Variation 92 |
| Avelumab + Axitinib | Trough Plasma Concentration (Ctrough) of Avelumab | Cycle 2 (day 29) | 22.62 Micrograms per milliliter | Geometric Coefficient of Variation 113 |
| Avelumab + Axitinib | Trough Plasma Concentration (Ctrough) of Avelumab | Cycle 3 (day 1) | 26.04 Micrograms per milliliter | Geometric Coefficient of Variation 98 |
| Avelumab + Axitinib | Trough Plasma Concentration (Ctrough) of Avelumab | Cycle 3 (day 29) | 30.13 Micrograms per milliliter | Geometric Coefficient of Variation 82 |
| Avelumab + Axitinib | Trough Plasma Concentration (Ctrough) of Avelumab | Cycle 4 (day 1) | 29.15 Micrograms per milliliter | Geometric Coefficient of Variation 98 |
| Avelumab + Axitinib | Trough Plasma Concentration (Ctrough) of Avelumab | Cycle 4 (day 29) | 31.38 Micrograms per milliliter | Geometric Coefficient of Variation 86 |
| Avelumab + Axitinib | Trough Plasma Concentration (Ctrough) of Avelumab | Cycle 6 (day 1) | 39.11 Micrograms per milliliter | Geometric Coefficient of Variation 58 |
Secondary
TTR as Assessed by Investigator in Participants Irrespective of PD-L1 Expression
TTR was defined as the time from randomization to the first documentation of objective tumor response according to RECIST v1.1 as assessed by investigator (CR or PR) which is subsequently confirmed. CR was defined as complete disappearance of all target and non-target lesions with the exception of nodal disease. All lymph nodes must decrease to normal size (short axis\<10 mm). All target lesions must be assessed. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. All target lesions must be assessed.
Time frame: From the date of randomization to the first documentation of objective response (CR or PR) (maximum up to approximately 89 months)
Population: FAS included all randomized participants. Here Number of Participants Analyzed signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Avelumab + Axitinib | TTR as Assessed by Investigator in Participants Irrespective of PD-L1 Expression | 2.8 Months |
| Sunitinib | TTR as Assessed by Investigator in Participants Irrespective of PD-L1 Expression | 2.8 Months |
Secondary
TTR in Biomarker-Positive Subgroup
TTR was defined as the time from randomization to the first documentation of objective tumor response (CR or PR) according to RECIST v1.1 which is subsequently confirmed. CR was defined as complete disappearance of all target and non-target lesions with the exception of nodal disease. All lymph nodes must decrease to normal size (short axis\<10 mm). All target lesions must be assessed. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. All target lesions must be assessed.
Time frame: From the date of randomization to the first documentation of objective response (CR or PR) (maximum up to approximately 26 months)
Population: Biomarker positive subset in FAS included participants who had at least one biomarker baseline assessment. Here Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Avelumab + Axitinib | TTR in Biomarker-Positive Subgroup | 1.6 Months |
| Sunitinib | TTR in Biomarker-Positive Subgroup | 3.0 Months |