Renal Cell Cancer
Conditions
Keywords
Cancer, renal cell cancer, kidney disease, kidney neoplasms, axitinib
Brief summary
This is a Phase 1b, open-label, multi-center, multiple-dose trial designed to estimate the maximum tolerated dose (MTD) and select the recommended phase 2 dose (RP2D) of avelumab (MSB0010718C) in combination with axitinib (AG-013736). Once the MTD of avelumab administered in combination with axitinib is estimated (dose finding portion), the dose expansion phase will be opened to further characterize the combination in term of safety profile, anti tumor activity, pharmacokinetics, pharmacodynamics and biomarker modulation.
Interventions
Avelumab with two dose levels: 10 mg/kg IV and 5 mg/kg IV every two weeks to find the maximum tolerated dose in combination with axitinib and continue treatment in a dose expansion.
Axitinib with two dose levels: 5 mg and 3 mg oral BID to find the maximum tolerated dose in combination with avelumab and continue treatment in a dose expansion.
Sponsors
Pfizer
Study design
Allocation
NA
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 RCC with clear cell component * Primary tumor resected * Availability of a recent 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 enrollment AND 2) the patient has not received any intervening systemic anti-cancer treatment from the time the tissue was obtained and enrollment onto the current study. If an FFPE tissue block cannot be provided as per documented regulations,, 15 unstained slides (10 minimum) will be acceptable. * Availability of an archival FFPE tumor tissue block from primary diagnosis specimen (if available and not provided per above). If an FFPE tissue block cannot be provided, 15 unstained slides (10 minimum) will be acceptable * At least one measureable lesion as defined by RECIST version 1.1 that has not been previously irradiated. * Age ≥18 years (≥ 20 years in Japan). * 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 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 as well as any prior therapies with other VEGF pathway inhibitors. * Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3), any history of anaphylaxis. * Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, 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 |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) | DLT observation period (from the beginning of Cycle 1 up to the end of Cycle 2 [28 days]) | DLT: greater than or equal to (\>=) Grade 3 hematologic/non-hematologic toxicity, Grade 3-4 liver-related laboratory test elevation (alanine aminotransferase, aspartate aminotransferase) with Grade 2 elevation of total bilirubin, non-hematologic Grade 3 laboratory abnormality (required medical intervention to treat participant/led to hospitalization), inability to complete \>=75% of first 2 cycles doses of axitinib (from Cycle 1 Day 1 after completion of lead-in period) or 2 infusions of avelumab within DLT observation period due to investigational product related toxicity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) | Baseline up to 30 days after the last dose of study treatment (maximum of 259.7 weeks) | Adverse event (AE)=any untoward medical occurrence in participant who received study treatment without regard to causality. TEAE=event between first dose of study treatment and up to 30 days after last dose that were absent before treatment or worsened relative to pretreatment state. Serious AE (SAE)=AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience; persistent or significant disability/incapacity; congenital anomaly. AEs were graded by worst National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 severity grade. Grade 3 event=unacceptable or intolerable event, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 event caused participant to be in imminent danger of death. Grade 5 event=death related to AE. The results reflect data available on cutoff of LPLV (04 Mar 2021). |
| Number of Participants With Treatment-related TEAEs | Baseline up to 30 days after the last dose of study treatment (maximum of 259.7 weeks) | Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. TEAE=event between first dose of study treatment and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience; persistent or significant disability/incapacity; congenital anomaly. AEs were graded by worst NCI CTCAE v4.03 severity grade. Grade 3 events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 events caused participant to be in imminent danger of death. Grade 5 events=death related to an AE. Treatment-related AEs and SAEs were determined by the investigator. The results reflect data available on cutoff of LPLV (04 Mar 2021). |
| Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | Baseline, Day 1 of each cycle, Day 8 of Cycles 1 and 2, end of treatment, Follow-up Days 30, 60, 90 for all participants in the analysis population, and Lead-in Day 7 for participants with lead-in (maximum of 139.6 weeks by PCD) | Blood pressure was taken with the participant in the seated position after the participant had been sitting quietly for at least 5 minutes. Baseline was defined as the last assessment prior to the date/time of the first dose of study treatment, which occurred on Day 1 in Lead-in period for participants with lead-in, and occurred on Cycle 1 Day 1 (C1D1) for participants without lead-in. The results reflect data available on cutoff of primary completion date (PCD) (03 Apr 2018). |
| Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology | Baseline up to 30 days after the last dose of study treatment and 1 day before the start day of new anti-cancer drug therapy (maximum of 259.7 weeks) | Laboratory abnormalities (hematology) reported included anemia, platelet count decreased, lymphocyte count decreased, and neutrophil count decreased. Grade 1=mild transient reaction; infusion interruption not indicated; intervention not indicated. Grade 2=therapy or infusion interruption indicated but responds promptly to symptomatic treatment; prophylactic medications indicated for \<=24 hours. Grade 3=prolonged; recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae. Grade 4=life threatening consequences; urgent intervention indicated. Grade 5=death. The results reflect data available on cutoff of LPLV (04 Mar 2021). |
| Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Baseline up to 30 days after the last dose of study treatment and 1 day before the start day of new anti-cancer drug therapy (maximum of 259.7 weeks) | Laboratory abnormalities (chemistry) reported included creatinine increased, serum amylase increased, lipase increased, alanine aminotransferase (ALT) increased, aspartate aminotransferase (AST) increased, blood bilirubin increased, creatine kinase increased, hypoglycemia, and hyperglycemia. Grade 1=mild transient reaction; infusion interruption not indicated; intervention not indicated. Grade 2=therapy or infusion interruption indicated but responds promptly to symptomatic treatment; prophylactic medications indicated for \<=24 hours. Grade 3=prolonged; recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae. Grade 4=life threatening consequences; urgent intervention indicated. Grade 5=death. The results reflect data available on cutoff of LPLV (04 Mar 2021). |
| Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | Baseline, Day 1 of each cycle, Day 8 of Cycles 1 and 2, end of treatment, Follow-up Days 30, 60, 90 for all participants in the analysis population, and Lead-in Day 7 for participants with lead-in (maximum of 139.6 weeks by PCD) | Blood pressure was taken with the participant in the seated position after the participant had been sitting quietly for at least 5 minutes. Baseline was defined as the last assessment prior to the date/time of the first dose of study treatment, which occurred on Day 1 in Lead-in period for participants with lead-in, and occurred on Cycle 1 Day 1 (C1D1) for participants without lead-in. The results reflect data available on cutoff of PCD (03 Apr 2018). |
| Change From Baseline in Vital Signs - Pulse Rate | Baseline, Day 1 of each cycle, Day 8 of Cycles 1 and 2, end of treatment, Follow-up Days 30, 60, 90 for all participants in the analysis population, and Lead-in Day 7 for participants with lead-in (maximum of 139.6 weeks by PCD) | Pulse rate was taken with the participant in the seated position after the participant had been sitting quietly for at least 5 minutes. Baseline was defined as the last assessment prior to the date/time of the first dose of study treatment, which occurred on Day 1 in Lead-in period for participants with lead-in, and occurred on Cycle 1 Day 1 (C1D1) for participants without lead-in. The results reflect data available on cutoff of PCD (03 Apr 2018). |
| Number of Participants Achieving Objective Response (OR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Cycle 1 Day 1 up to 30 months after the first dose | Confirmed OR was defined as complete response (CR) or partial response (PR) according to RECIST v1.1 from the start date until disease progression or death due to any cause. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \<10 mm). PR was defined as \>= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must have been assessed. The results reflect data available on cutoff of PCD (03 Apr 2018). |
| Number of Participants Achieving Disease Control (DC) Based on RECIST Version 1.1 | Cycle 1 Day 1 up to 30 months after the first dose | DC was defined as OR (CR or PR) or stable disease (SD) per RECIST v1.1 from the start date until the first documentation of objective disease progression or death due to any cause. SD was defined as not qualifying for CR, PR, or progression (PD). PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \<10 mm). PR was defined as \>= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must have been assessed. The results reflect data available on cutoff of PCD (03 Apr 2018). |
| Duration of Response (DR) Based on RECIST Version 1.1 | Cycle 1 Day 1 up to 30 months after the first dose | DR was defined as the time from the first documentation of objective tumor response (CR or PR) that was subsequently confirmed to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \<10 mm). PR was defined as \>= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must have been assessed. The results reflect data available on cutoff of PCD (03 Apr 2018). |
| Time for Cmax (Tmax) for Axitinib When Dosed Alone and in Combination With Avelumab | Predose, 1, 2, 3, 4, 6, and 8 hours post dose on Lead-in Day 7 and Cycle 4 Day 1 | Tmax for axitinib when dosed alone on Lead-in Day 7 and in combination with avelumab on Cycle 4 Day 1 for Axitinib + Avelumab with Lead-in Arm. The results reflect data available on cutoff of PCD (03 Apr 2018). |
| Time to Tumor Response (TTR) Based on RECIST Version 1.1 | Cycle 1 Day 1 up to 30 months after the first dose | TTR was defined as the time from start date to the first documentation of objective tumor response (CR or PR) that was subsequently confirmed. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \<10 mm). PR was defined as \>= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must have been assessed. The results reflect data available on cutoff of PCD (03 Apr 2018). |
| Overall Survival (OS) | Cycle 1 Day 1 up to 30 months after the first dose | OS was defined as the time from the start date to the date of death due to any cause. The results reflect data available on cutoff of PCD (03 Apr 2018). |
| Maximum Observed Plasma Concentration (Cmax) for Axitinib When Dosed Alone and in Combination With Avelumab | Predose, 1, 2, 3, 4, 6, and 8 hours post dose on Lead-in Day 7 and Cycle 4 Day 1 | Cmax for axitinib when dosed alone on Lead-in Day 7 and in combination with avelumab on Cycle 4 Day 1 for Axitinib + Avelumab with Lead-in Arm. The results reflect data available on cutoff of PCD (03 Apr 2018). |
| Area Under the Plasma Concentration Time Profile From Time Zero to the Next Dose at Steady State (AUCtau) for Axitinib When Dosed Alone and in Combination With Avelumab | Predose, 1, 2, 3, 4, 6, and 8 hours post dose on Lead-in Day 7 and Cycle 4 Day 1 | AUCtau was defined as area under the plasma concentration time profile from time zero to time tau, the dosing interval at steady state. tau = 12 hrs for Axitinib. AUCtau for Axitinib when dosed alone on Lead-in Day 7 and in combination with avelumab on Cycle 4 Day 1 for Axitinib + Avelumab with Lead-in Arm was reported. The results reflect data available on cutoff of PCD (03 Apr 2018). |
| Terminal Half-Life (t1/2) for Axitinib When Dosed Alone and in Combination With Avelumab | Predose, 1, 2, 3, 4, 6, and 8 hours post dose on Lead-in Day 7 and Cycle 4 Day 1 | t1/2 was calculated by Log e(2)/kel. kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration time-curve. Only those data points judged to describe the terminal log linear decline were used in the regression. t1/2 for Axitinib when dosed alone on Lead-in Day 7 and in combination with avelumab on Cycle 4 Day 1 for Axitinib + Avelumab with Lead-in Arm was reported. The results reflect data available on cutoff of PCD (03 Apr 2018). |
| Predose Concentration During Multiple Dosing (Ctrough) for Avelumab | Predose on Day 1 of Cycles 1, 2, 3, 4, 6, 8, 14, 20, 26, 32, 38, 44, and 50 | Ctrough was directly observed from data. The results reflect data available on cutoff of PCD (03 Apr 2018). |
| Cmax for Avelumab | Predose, 1 hour, and 168 hours post dose on Cycle 1 Day 1; predose and 1 hour post dose on Cycle 4 Day 1 | Cmax for avelumab on Cycle 1 Day (C1D1) and C1D4 were reported. The results reflect data available on cutoff of PCD (03 Apr 2018). |
| Number of Participants With Their Target Programmed Death-Ligand (PD-L1) Status at Baseline | Baseline | Number of participants with PD-L1 positive (PD-L1 \>=1%) status in immune cell (IC), tumor cell (TC), or both IC and TC. The results reflect data available on cutoff of PCD (03 Apr 2018). |
| Number of Participants With Anti-drug Antibody (ADA) Against Avelumab When Combined With Axitinib by Never and Ever Positive Status | Pre-dose on Day 1 of Cycles 1-4, 6, 8, then every 12 weeks thereafter until Cycle 50, and on Follow-up Day 30 (maximum of 2 years) | Whole blood specimens were collected at the designated times (Day 1 of Cycles 1-4, 6, and 8, then every 12 weeks until Cycle 50, and Follow-up Day 30) to provide serum for evaluation of avelumab immunogenicity. Human serum ADA specimens were analyzed for the presence or absence of anti-avelumab antibodies with quasi-quantitative enzyme-linked immunosorbent assay, following a tiered approach using screening, confirmation and titer/quantitation. ADA serum specimens were screened at tier 1. In the event that there were no positive specimens, no further analyses were to be conducted. If positive specimens were identified, these specimens were further tested with the confirmatory assay to confirm as positive. Number of participants with ADA positive at baseline, ADA never-positive, ADA ever-positive, treatment-boosted ADA, treatment-induced ADA, transient ADA response, or persistent ADA response from baseline up to 2 years. The results reflect data available on cutoff of PCD (03 Apr 2018). |
| Progression-free Survival (PFS) | Cycle 1 Day 1 up to 30 months after the first dose | PFS was defined as defined as the time from the start date to the date of the first documentation of objective progression of disease (PD) or death due to any cause, whichever occurred first. PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm. All target lesions must have been assessed. The results reflect data available on cutoff of PCD (03 Apr 2018). |
Countries
Japan, United Kingdom, United States
Participant flow
Pre-assignment details
In this study, a lead-in period was conducted (only axitinib administered) in few participants prior to the administration of combination treatment (axitinib+avelumab) in treatment period. After 5 years from study initiation, the study was closed by Sponsor due to an internal decision (ie, end of study). No safety concerns were related to the study closure. Data reported based on last participant last visit (LPLV) date (04 March 2021).
Participants by arm
| Arm | Count |
|---|---|
| Axitinib + Avelumab With Lead-in Participants received 5 mg axitinib tablets orally twice daily for 7 days in lead-in period (7 days) followed by 10 milligram/ kilogram (mg/kg) avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 255.4 weeks). | 16 |
| Axitinib + Avelumab Participants received 10 mg/kg avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 240.1 weeks). | 39 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 6 | 13 |
| Overall Study | Lost to Follow-up | 2 | 3 |
| Overall Study | Study closed by Sponsor due to an internal decision with no safety concerns related. | 6 | 15 |
| Overall Study | Withdrawal by Subject | 2 | 8 |
Baseline characteristics
| Characteristic | Axitinib + Avelumab | Axitinib + Avelumab With Lead-in | Total |
|---|---|---|---|
| Age, Continuous | 60.5 years STANDARD_DEVIATION 8.89 | 60.0 years STANDARD_DEVIATION 8.45 | 60.3 years STANDARD_DEVIATION 8.69 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 35 Participants | 16 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 6 Participants | 0 Participants | 6 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 29 Participants | 15 Participants | 44 Participants |
| Sex: Female, Male Female | 11 Participants | 2 Participants | 13 Participants |
| Sex: Female, Male Male | 28 Participants | 14 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 6 / 16 | 14 / 39 |
| other Total, other adverse events | 16 / 16 | 39 / 39 |
| serious Total, serious adverse events | 6 / 16 | 18 / 39 |
Outcome results
Primary
Number of Participants With Dose Limiting Toxicities (DLTs)
DLT: greater than or equal to (\>=) Grade 3 hematologic/non-hematologic toxicity, Grade 3-4 liver-related laboratory test elevation (alanine aminotransferase, aspartate aminotransferase) with Grade 2 elevation of total bilirubin, non-hematologic Grade 3 laboratory abnormality (required medical intervention to treat participant/led to hospitalization), inability to complete \>=75% of first 2 cycles doses of axitinib (from Cycle 1 Day 1 after completion of lead-in period) or 2 infusions of avelumab within DLT observation period due to investigational product related toxicity.
Time frame: DLT observation period (from the beginning of Cycle 1 up to the end of Cycle 2 [28 days])
Population: DLT evaluable analysis set: First 6 enrolled participants who received at least 1 dose of avelumab and axitinib, and either experienced DLT during DLT observation period or completed it. Data for this endpoint was only planned to be collected and analyzed for Axitinib + Avelumab with Lead-in arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Axitinib + Avelumab With Lead-in | Number of Participants With Dose Limiting Toxicities (DLTs) | 1 Participants |
Secondary
Area Under the Plasma Concentration Time Profile From Time Zero to the Next Dose at Steady State (AUCtau) for Axitinib When Dosed Alone and in Combination With Avelumab
AUCtau was defined as area under the plasma concentration time profile from time zero to time tau, the dosing interval at steady state. tau = 12 hrs for Axitinib. AUCtau for Axitinib when dosed alone on Lead-in Day 7 and in combination with avelumab on Cycle 4 Day 1 for Axitinib + Avelumab with Lead-in Arm was reported. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time frame: Predose, 1, 2, 3, 4, 6, and 8 hours post dose on Lead-in Day 7 and Cycle 4 Day 1
Population: The population for this outcome measure included all enrolled participants who received at least 1 dose of avelumab or axitinib and who had at least 1 of the pharmacokinetic (PK) parameters of interest of either study drug.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Axitinib + Avelumab With Lead-in | Area Under the Plasma Concentration Time Profile From Time Zero to the Next Dose at Steady State (AUCtau) for Axitinib When Dosed Alone and in Combination With Avelumab | Lean-in Day 7 | 113.11 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 206 |
| Axitinib + Avelumab With Lead-in | Area Under the Plasma Concentration Time Profile From Time Zero to the Next Dose at Steady State (AUCtau) for Axitinib When Dosed Alone and in Combination With Avelumab | Cycle 4 Day 1 | 95.60 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 162 |
Secondary
Change From Baseline in Vital Signs - Pulse Rate
Pulse rate was taken with the participant in the seated position after the participant had been sitting quietly for at least 5 minutes. Baseline was defined as the last assessment prior to the date/time of the first dose of study treatment, which occurred on Day 1 in Lead-in period for participants with lead-in, and occurred on Cycle 1 Day 1 (C1D1) for participants without lead-in. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time frame: Baseline, Day 1 of each cycle, Day 8 of Cycles 1 and 2, end of treatment, Follow-up Days 30, 60, 90 for all participants in the analysis population, and Lead-in Day 7 for participants with lead-in (maximum of 139.6 weeks by PCD)
Population: The population for this outcome measure included all enrolled participants who received at least 1 dose of avelumab or axitinib (ie, safety analysis set). Number of Participants Analyzed represents the total number of participants in the safety analysis set. Number Analyzed in each row represents the number of participants in the safety analysis set with at least 1 baseline and 1 post-baseline assessments at the visit.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C16D1 | -1.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C34D1 | -1.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C3D1 | 4.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C35D1 | -2.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C17D1 | -6.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C36D1 | 1.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C8D1 | -6.5 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C37D1 | 1.5 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C18D1 | 0.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C38D1 | -1.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C2D1 | 3.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C39D1 | 0.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C59D1 | 2.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C19D1 | -1.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C40D1 | -3.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C9D1 | -1.5 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C41D1 | -5.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C20D1 | 2.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C42D1 | -3.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C4D1 | 1.5 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C43D1 | 4.5 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C21D1 | -1.5 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C44D1 | 2.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C10D1 | -3.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C60D1 | 1.5 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C45D1 | 2.5 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C22D1 | 0.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C46D1 | 1.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C1D8 | -2.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C47D1 | 5.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C23D1 | 2.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C48D1 | -3.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C11D1 | -2.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C49D1 | 10.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C24D1 | -3.5 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C50D1 | -2.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C5D1 | 0.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C51D1 | 0.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C25D1 | 0.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C52D1 | 0.5 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C12D1 | -6.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C53D1 | 6.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C26D1 | -4.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C54D1 | 2.5 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C2D8 | 8.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C55D1 | -6.5 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C27D1 | 1.5 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C56D1 | 1.5 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C13D1 | -1.5 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C57D1 | -4.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C58D1 | 4.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C61D1 | 2.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C62D1 | 9.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | End of Treatment | 2.5 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C28D1 | -8.5 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | Follow-up Day 30 | -1.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C6D1 | -3.5 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | Follow-up Day 60 | 2.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C29D1 | -6.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | Follow-up Day 90 | 9.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | Lean-in Day 7 | -0.5 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C14D1 | 1.5 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C30D1 | -3.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C1D1 | -1.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C31D1 | 1.5 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C15D1 | -4.5 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C32D1 | 2.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C7D1 | 1.0 beats per minute (bpm) |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Pulse Rate | C33D1 | -4.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | Follow-up Day 90 | 5.5 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C1D8 | -2.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C2D1 | 4.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C2D8 | 2.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C3D1 | 2.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C4D1 | 4.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C5D1 | 2.5 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C6D1 | 3.5 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C7D1 | 1.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C8D1 | -1.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C9D1 | 1.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C10D1 | 3.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C11D1 | 3.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C12D1 | 1.5 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C13D1 | 2.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C14D1 | 5.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C15D1 | -3.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C16D1 | 1.5 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C17D1 | 1.5 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C18D1 | 3.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C19D1 | -3.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C20D1 | 1.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C21D1 | 2.5 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C22D1 | -6.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C23D1 | -3.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C24D1 | 0.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C25D1 | -4.5 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C26D1 | -3.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C27D1 | 0.5 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C28D1 | 0.5 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C29D1 | -4.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C30D1 | -2.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C31D1 | -3.5 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C32D1 | 2.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C33D1 | 1.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C34D1 | 1.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C35D1 | 2.5 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C36D1 | 0.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C37D1 | 0.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C38D1 | 2.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C39D1 | -1.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C40D1 | 2.5 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C41D1 | 1.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C42D1 | 0.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C43D1 | 1.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C44D1 | 5.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C45D1 | 9.5 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C46D1 | 11.5 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C47D1 | 5.5 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C48D1 | 4.5 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C49D1 | -0.5 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C50D1 | 4.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C51D1 | 6.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C52D1 | 3.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C53D1 | 10.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C54D1 | 1.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C55D1 | 5.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | C56D1 | 1.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | End of Treatment | 6.5 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | Follow-up Day 30 | -2.0 beats per minute (bpm) |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Pulse Rate | Follow-up Day 60 | 3.0 beats per minute (bpm) |
Secondary
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure
Blood pressure was taken with the participant in the seated position after the participant had been sitting quietly for at least 5 minutes. Baseline was defined as the last assessment prior to the date/time of the first dose of study treatment, which occurred on Day 1 in Lead-in period for participants with lead-in, and occurred on Cycle 1 Day 1 (C1D1) for participants without lead-in. The results reflect data available on cutoff of primary completion date (PCD) (03 Apr 2018).
Time frame: Baseline, Day 1 of each cycle, Day 8 of Cycles 1 and 2, end of treatment, Follow-up Days 30, 60, 90 for all participants in the analysis population, and Lead-in Day 7 for participants with lead-in (maximum of 139.6 weeks by PCD)
Population: The population for this outcome measure included all enrolled participants who received at least 1 dose of avelumab or axitinib (ie, safety analysis set). Number of Participants Analyzed represents the total number of participants in the safety analysis set. Number Analyzed in each row represents the number of participants in the safety analysis set with at least 1 baseline and 1 post-baseline assessments at the visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C16D1 | 7.5 millimeter of mercury (mm Hg) | Standard Deviation 10.33 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C34D1 | 3.5 millimeter of mercury (mm Hg) | Standard Deviation 13.67 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C3D1 | 6.1 millimeter of mercury (mm Hg) | Standard Deviation 12.16 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C35D1 | 7.2 millimeter of mercury (mm Hg) | Standard Deviation 9.76 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C17D1 | 6.2 millimeter of mercury (mm Hg) | Standard Deviation 9.84 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C36D1 | 7.5 millimeter of mercury (mm Hg) | Standard Deviation 9.4 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C8D1 | 5.7 millimeter of mercury (mm Hg) | Standard Deviation 10.76 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C37D1 | 9.9 millimeter of mercury (mm Hg) | Standard Deviation 10.47 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C18D1 | 4.3 millimeter of mercury (mm Hg) | Standard Deviation 8.45 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C38D1 | 5.0 millimeter of mercury (mm Hg) | Standard Deviation 8.92 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C2D1 | 3.4 millimeter of mercury (mm Hg) | Standard Deviation 13.15 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C39D1 | 6.6 millimeter of mercury (mm Hg) | Standard Deviation 10.1 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C19D1 | 6.3 millimeter of mercury (mm Hg) | Standard Deviation 7.58 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C40D1 | 7.8 millimeter of mercury (mm Hg) | Standard Deviation 10.75 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C9D1 | 3.9 millimeter of mercury (mm Hg) | Standard Deviation 10.8 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C41D1 | 6.6 millimeter of mercury (mm Hg) | Standard Deviation 9.76 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C20D1 | 7.9 millimeter of mercury (mm Hg) | Standard Deviation 6.71 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C42D1 | 5.9 millimeter of mercury (mm Hg) | Standard Deviation 9.35 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C4D1 | 3.6 millimeter of mercury (mm Hg) | Standard Deviation 10.34 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C43D1 | 13.0 millimeter of mercury (mm Hg) | Standard Deviation 11.53 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C21D1 | 8.9 millimeter of mercury (mm Hg) | Standard Deviation 9.35 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C44D1 | 8.3 millimeter of mercury (mm Hg) | Standard Deviation 11.04 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C10D1 | 7.3 millimeter of mercury (mm Hg) | Standard Deviation 9.8 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C45D1 | 8.1 millimeter of mercury (mm Hg) | Standard Deviation 10.23 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C22D1 | 7.2 millimeter of mercury (mm Hg) | Standard Deviation 9.34 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C46D1 | 11.1 millimeter of mercury (mm Hg) | Standard Deviation 11.27 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C1D8 | 3.2 millimeter of mercury (mm Hg) | Standard Deviation 12.8 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C47D1 | 8.4 millimeter of mercury (mm Hg) | Standard Deviation 13.62 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C23D1 | 9.2 millimeter of mercury (mm Hg) | Standard Deviation 9.54 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C48D1 | 6.3 millimeter of mercury (mm Hg) | Standard Deviation 9.75 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C11D1 | 7.4 millimeter of mercury (mm Hg) | Standard Deviation 8.98 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C49D1 | 9.4 millimeter of mercury (mm Hg) | Standard Deviation 10.67 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C24D1 | 7.3 millimeter of mercury (mm Hg) | Standard Deviation 8.42 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C50D1 | 9.0 millimeter of mercury (mm Hg) | Standard Deviation 9.27 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C5D1 | 4.8 millimeter of mercury (mm Hg) | Standard Deviation 10.53 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C51D1 | 9.3 millimeter of mercury (mm Hg) | Standard Deviation 10.17 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C25D1 | 3.1 millimeter of mercury (mm Hg) | Standard Deviation 9.62 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C52D1 | 9.3 millimeter of mercury (mm Hg) | Standard Deviation 11.6 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C12D1 | 5.3 millimeter of mercury (mm Hg) | Standard Deviation 8.2 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C53D1 | 15.4 millimeter of mercury (mm Hg) | Standard Deviation 18.37 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C26D1 | 5.6 millimeter of mercury (mm Hg) | Standard Deviation 9.65 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C54D1 | 12.5 millimeter of mercury (mm Hg) | Standard Deviation 7.42 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C2D8 | 1.8 millimeter of mercury (mm Hg) | Standard Deviation 10.01 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C55D1 | 16.0 millimeter of mercury (mm Hg) | Standard Deviation 19.71 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C27D1 | 4.5 millimeter of mercury (mm Hg) | Standard Deviation 8.64 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C56D1 | 10.0 millimeter of mercury (mm Hg) | Standard Deviation 13.74 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C13D1 | 6.0 millimeter of mercury (mm Hg) | Standard Deviation 7.71 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C57D1 | 14.5 millimeter of mercury (mm Hg) | Standard Deviation 12.15 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C58D1 | 16.5 millimeter of mercury (mm Hg) | Standard Deviation 12.82 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C59D1 | 26.5 millimeter of mercury (mm Hg) | Standard Deviation 9.19 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C60D1 | 22.5 millimeter of mercury (mm Hg) | Standard Deviation 4.95 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C61D1 | 24.5 millimeter of mercury (mm Hg) | Standard Deviation 4.95 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C62D1 | 22.0 millimeter of mercury (mm Hg) | Standard Deviation 1.41 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | End of Treatment | -1.6 millimeter of mercury (mm Hg) | Standard Deviation 10.38 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C28D1 | 4.9 millimeter of mercury (mm Hg) | Standard Deviation 7.53 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | Follow-up Day 30 | -3.2 millimeter of mercury (mm Hg) | Standard Deviation 8.41 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C6D1 | 3.0 millimeter of mercury (mm Hg) | Standard Deviation 9.84 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | Follow-up Day 60 | -4.7 millimeter of mercury (mm Hg) | Standard Deviation 10.26 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C29D1 | 5.4 millimeter of mercury (mm Hg) | Standard Deviation 9.9 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | Follow-up Day 90 | -2.0 millimeter of mercury (mm Hg) | Standard Deviation 4.58 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | Lead-in Day 7 | 5.4 millimeter of mercury (mm Hg) | Standard Deviation 9.32 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C14D1 | 5.4 millimeter of mercury (mm Hg) | Standard Deviation 10.87 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C30D1 | 5.6 millimeter of mercury (mm Hg) | Standard Deviation 8.53 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C1D1 | 4.1 millimeter of mercury (mm Hg) | Standard Deviation 9.36 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C31D1 | 4.8 millimeter of mercury (mm Hg) | Standard Deviation 11.4 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C15D1 | 6.9 millimeter of mercury (mm Hg) | Standard Deviation 6.56 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C32D1 | 7.1 millimeter of mercury (mm Hg) | Standard Deviation 11.06 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C7D1 | 4.8 millimeter of mercury (mm Hg) | Standard Deviation 11.82 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C33D1 | 5.5 millimeter of mercury (mm Hg) | Standard Deviation 6.59 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | Follow-up Day 90 | 1.3 millimeter of mercury (mm Hg) | Standard Deviation 6.18 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C1D8 | 9.8 millimeter of mercury (mm Hg) | Standard Deviation 11.81 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C2D1 | 10.1 millimeter of mercury (mm Hg) | Standard Deviation 10.03 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C2D8 | 14.7 millimeter of mercury (mm Hg) | Standard Deviation 5.03 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C3D1 | 10.2 millimeter of mercury (mm Hg) | Standard Deviation 11.8 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C4D1 | 8.8 millimeter of mercury (mm Hg) | Standard Deviation 9.6 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C5D1 | 6.9 millimeter of mercury (mm Hg) | Standard Deviation 11.64 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C6D1 | 7.5 millimeter of mercury (mm Hg) | Standard Deviation 11.76 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C7D1 | 7.5 millimeter of mercury (mm Hg) | Standard Deviation 12.5 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C8D1 | 9.0 millimeter of mercury (mm Hg) | Standard Deviation 10.86 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C9D1 | 10.0 millimeter of mercury (mm Hg) | Standard Deviation 13.44 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C10D1 | 7.7 millimeter of mercury (mm Hg) | Standard Deviation 8.97 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C11D1 | 7.5 millimeter of mercury (mm Hg) | Standard Deviation 11.09 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C12D1 | 6.6 millimeter of mercury (mm Hg) | Standard Deviation 12.07 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C13D1 | 10.5 millimeter of mercury (mm Hg) | Standard Deviation 11.92 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C14D1 | 7.2 millimeter of mercury (mm Hg) | Standard Deviation 14.04 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C15D1 | 7.6 millimeter of mercury (mm Hg) | Standard Deviation 12.13 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C16D1 | 5.8 millimeter of mercury (mm Hg) | Standard Deviation 13.57 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C17D1 | 6.4 millimeter of mercury (mm Hg) | Standard Deviation 13.2 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C18D1 | 5.1 millimeter of mercury (mm Hg) | Standard Deviation 12.22 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C19D1 | 5.5 millimeter of mercury (mm Hg) | Standard Deviation 10.67 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C20D1 | 6.9 millimeter of mercury (mm Hg) | Standard Deviation 11.69 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C21D1 | 6.6 millimeter of mercury (mm Hg) | Standard Deviation 10.22 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C22D1 | 6.2 millimeter of mercury (mm Hg) | Standard Deviation 11.96 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C23D1 | 4.5 millimeter of mercury (mm Hg) | Standard Deviation 11.52 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C24D1 | 4.3 millimeter of mercury (mm Hg) | Standard Deviation 12.91 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C25D1 | 6.0 millimeter of mercury (mm Hg) | Standard Deviation 13.34 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C26D1 | 7.8 millimeter of mercury (mm Hg) | Standard Deviation 12.33 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C27D1 | 6.2 millimeter of mercury (mm Hg) | Standard Deviation 13.39 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C28D1 | 6.2 millimeter of mercury (mm Hg) | Standard Deviation 13.35 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C29D1 | 7.1 millimeter of mercury (mm Hg) | Standard Deviation 11.13 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C30D1 | 6.1 millimeter of mercury (mm Hg) | Standard Deviation 13.32 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C31D1 | 6.7 millimeter of mercury (mm Hg) | Standard Deviation 10.41 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C32D1 | 7.6 millimeter of mercury (mm Hg) | Standard Deviation 13.52 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C33D1 | 3.6 millimeter of mercury (mm Hg) | Standard Deviation 13.67 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C34D1 | 5.0 millimeter of mercury (mm Hg) | Standard Deviation 15.71 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C35D1 | 8.1 millimeter of mercury (mm Hg) | Standard Deviation 12.46 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C36D1 | 10.9 millimeter of mercury (mm Hg) | Standard Deviation 11.31 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C37D1 | 7.6 millimeter of mercury (mm Hg) | Standard Deviation 13.32 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C38D1 | 6.9 millimeter of mercury (mm Hg) | Standard Deviation 12.73 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C39D1 | 7.9 millimeter of mercury (mm Hg) | Standard Deviation 14.61 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C40D1 | 6.0 millimeter of mercury (mm Hg) | Standard Deviation 13.08 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C41D1 | 8.4 millimeter of mercury (mm Hg) | Standard Deviation 11.7 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C42D1 | 5.7 millimeter of mercury (mm Hg) | Standard Deviation 13.64 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C43D1 | 2.5 millimeter of mercury (mm Hg) | Standard Deviation 7.73 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C44D1 | 6.6 millimeter of mercury (mm Hg) | Standard Deviation 10.08 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C45D1 | 5.4 millimeter of mercury (mm Hg) | Standard Deviation 13.16 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C46D1 | 3.0 millimeter of mercury (mm Hg) | Standard Deviation 14.03 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C47D1 | 1.1 millimeter of mercury (mm Hg) | Standard Deviation 12.01 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C48D1 | 3.9 millimeter of mercury (mm Hg) | Standard Deviation 13.37 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C49D1 | 11.8 millimeter of mercury (mm Hg) | Standard Deviation 11.44 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C50D1 | 7.0 millimeter of mercury (mm Hg) | Standard Deviation 11.53 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C51D1 | 4.3 millimeter of mercury (mm Hg) | Standard Deviation 10.14 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C52D1 | 8.2 millimeter of mercury (mm Hg) | Standard Deviation 11.48 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C53D1 | 2.0 millimeter of mercury (mm Hg) | Standard Deviation 14.72 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C54D1 | 0.3 millimeter of mercury (mm Hg) | Standard Deviation 12.66 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C55D1 | -3.0 millimeter of mercury (mm Hg) | — |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | C56D1 | 0.0 millimeter of mercury (mm Hg) | — |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | End of Treatment | 2.5 millimeter of mercury (mm Hg) | Standard Deviation 13.05 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | Follow-up Day 30 | -2.9 millimeter of mercury (mm Hg) | Standard Deviation 12.51 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure | Follow-up Day 60 | 3.8 millimeter of mercury (mm Hg) | Standard Deviation 8.33 |
Secondary
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure
Blood pressure was taken with the participant in the seated position after the participant had been sitting quietly for at least 5 minutes. Baseline was defined as the last assessment prior to the date/time of the first dose of study treatment, which occurred on Day 1 in Lead-in period for participants with lead-in, and occurred on Cycle 1 Day 1 (C1D1) for participants without lead-in. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time frame: Baseline, Day 1 of each cycle, Day 8 of Cycles 1 and 2, end of treatment, Follow-up Days 30, 60, 90 for all participants in the analysis population, and Lead-in Day 7 for participants with lead-in (maximum of 139.6 weeks by PCD)
Population: The population for this outcome measure included all enrolled participants who received at least 1 dose of avelumab or axitinib (ie, safety analysis set). Number of Participants Analyzed represents the total number of participants in the safety analysis set. Number Analyzed in each row represents the number of participants in the safety analysis set with at least 1 baseline and 1 post-baseline assessments at the visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C16D1 | 6.2 mm Hg | Standard Deviation 13.46 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C34D1 | 2.8 mm Hg | Standard Deviation 18.79 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C3D1 | 9.9 mm Hg | Standard Deviation 18.96 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C35D1 | 10.3 mm Hg | Standard Deviation 13.47 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C17D1 | 7.3 mm Hg | Standard Deviation 15.55 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C36D1 | 9.0 mm Hg | Standard Deviation 12.92 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C8D1 | 13.5 mm Hg | Standard Deviation 12.07 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C37D1 | 10.2 mm Hg | Standard Deviation 11.48 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C18D1 | 3.5 mm Hg | Standard Deviation 14.67 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C38D1 | 8.3 mm Hg | Standard Deviation 11.83 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C2D1 | 4.6 mm Hg | Standard Deviation 18.49 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C39D1 | 3.8 mm Hg | Standard Deviation 13.33 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C19D1 | 5.8 mm Hg | Standard Deviation 16.04 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C40D1 | 10.9 mm Hg | Standard Deviation 14.13 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C9D1 | 11.4 mm Hg | Standard Deviation 14.24 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C41D1 | 7.9 mm Hg | Standard Deviation 16.74 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C20D1 | 8.3 mm Hg | Standard Deviation 9.67 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C42D1 | 11.6 mm Hg | Standard Deviation 15.74 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C4D1 | 6.7 mm Hg | Standard Deviation 15.61 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C43D1 | 12.3 mm Hg | Standard Deviation 13.2 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C21D1 | 5.0 mm Hg | Standard Deviation 14.14 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C44D1 | 9.6 mm Hg | Standard Deviation 21.41 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C10D1 | 8.9 mm Hg | Standard Deviation 16.83 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C45D1 | 9.1 mm Hg | Standard Deviation 17.71 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C22D1 | 2.9 mm Hg | Standard Deviation 14.53 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C46D1 | 6.1 mm Hg | Standard Deviation 11.28 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C1D8 | 8.0 mm Hg | Standard Deviation 18.94 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C47D1 | 6.6 mm Hg | Standard Deviation 18.31 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C23D1 | 9.3 mm Hg | Standard Deviation 14.19 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C48D1 | -0.1 mm Hg | Standard Deviation 15.04 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C11D1 | 7.8 mm Hg | Standard Deviation 15.36 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C49D1 | 5.4 mm Hg | Standard Deviation 13.73 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C24D1 | 9.1 mm Hg | Standard Deviation 12.55 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C50D1 | 9.7 mm Hg | Standard Deviation 10.5 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C5D1 | 6.2 mm Hg | Standard Deviation 19.45 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C51D1 | 13.5 mm Hg | Standard Deviation 13.85 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C25D1 | 4.0 mm Hg | Standard Deviation 12.78 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C52D1 | 4.3 mm Hg | Standard Deviation 16.17 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C12D1 | 6.8 mm Hg | Standard Deviation 11.27 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C53D1 | 17.0 mm Hg | Standard Deviation 16.29 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C26D1 | 2.8 mm Hg | Standard Deviation 15.86 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C54D1 | 10.8 mm Hg | Standard Deviation 14.2 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C2D8 | 0.8 mm Hg | Standard Deviation 15.63 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C55D1 | 15.8 mm Hg | Standard Deviation 19.17 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C27D1 | 5.4 mm Hg | Standard Deviation 14.74 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C56D1 | 8.5 mm Hg | Standard Deviation 11.62 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C13D1 | 7.3 mm Hg | Standard Deviation 11.17 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C57D1 | 11.5 mm Hg | Standard Deviation 12.23 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C58D1 | 8.0 mm Hg | Standard Deviation 17.45 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C59D1 | 21.5 mm Hg | Standard Deviation 4.95 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C60D1 | 22.0 mm Hg | Standard Deviation 19.8 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C61D1 | 20.0 mm Hg | Standard Deviation 15.56 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C62D1 | 14.5 mm Hg | Standard Deviation 13.44 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | End of Treatment | 11.3 mm Hg | Standard Deviation 25.45 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C28D1 | 7.8 mm Hg | Standard Deviation 14.49 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | Follow-up Day 30 | 15.0 mm Hg | Standard Deviation 20.65 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C6D1 | 6.5 mm Hg | Standard Deviation 15.05 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | Follow-up Day 60 | 16.0 mm Hg | Standard Deviation 9.54 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C29D1 | 3.3 mm Hg | Standard Deviation 14.28 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | Follow-up Day 90 | 20.7 mm Hg | Standard Deviation 13.32 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | Lead-in Day 7 | 9.7 mm Hg | Standard Deviation 13.44 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C14D1 | 5.8 mm Hg | Standard Deviation 15.49 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C30D1 | 6.4 mm Hg | Standard Deviation 13.57 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C1D1 | 11.0 mm Hg | Standard Deviation 18.2 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C31D1 | 2.7 mm Hg | Standard Deviation 13.14 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C15D1 | 7.3 mm Hg | Standard Deviation 13.89 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C32D1 | 8.6 mm Hg | Standard Deviation 16.71 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C7D1 | 10.2 mm Hg | Standard Deviation 14.46 |
| Axitinib + Avelumab With Lead-in | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C33D1 | 2.9 mm Hg | Standard Deviation 16.07 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | Follow-up Day 90 | 9.3 mm Hg | Standard Deviation 10.24 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C1D8 | 10.3 mm Hg | Standard Deviation 16.12 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C2D1 | 11.2 mm Hg | Standard Deviation 11.47 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C2D8 | 17.7 mm Hg | Standard Deviation 6.66 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C3D1 | 8.7 mm Hg | Standard Deviation 15.05 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C4D1 | 5.8 mm Hg | Standard Deviation 11.73 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C5D1 | 6.7 mm Hg | Standard Deviation 14.9 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C6D1 | 5.2 mm Hg | Standard Deviation 13.34 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C7D1 | 6.1 mm Hg | Standard Deviation 14.49 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C8D1 | 8.0 mm Hg | Standard Deviation 15.14 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C9D1 | 10.2 mm Hg | Standard Deviation 16.29 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C10D1 | 8.4 mm Hg | Standard Deviation 15.69 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C11D1 | 7.2 mm Hg | Standard Deviation 14.83 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C12D1 | 4.1 mm Hg | Standard Deviation 14.29 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C13D1 | 8.6 mm Hg | Standard Deviation 16.01 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C14D1 | 3.9 mm Hg | Standard Deviation 17.66 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C15D1 | 7.3 mm Hg | Standard Deviation 20.46 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C16D1 | 5.5 mm Hg | Standard Deviation 16.8 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C17D1 | 3.5 mm Hg | Standard Deviation 17.32 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C18D1 | 4.2 mm Hg | Standard Deviation 15.07 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C19D1 | 2.6 mm Hg | Standard Deviation 14.15 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C20D1 | 1.1 mm Hg | Standard Deviation 12.2 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C21D1 | 3.1 mm Hg | Standard Deviation 10.17 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C22D1 | 0.2 mm Hg | Standard Deviation 14.31 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C23D1 | 1.5 mm Hg | Standard Deviation 15.05 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C24D1 | -0.1 mm Hg | Standard Deviation 16.57 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C25D1 | 3.5 mm Hg | Standard Deviation 15.28 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C26D1 | 3.4 mm Hg | Standard Deviation 15.82 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C27D1 | 1.6 mm Hg | Standard Deviation 16.13 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C28D1 | 2.1 mm Hg | Standard Deviation 16.65 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C29D1 | 4.1 mm Hg | Standard Deviation 11.82 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C30D1 | 2.9 mm Hg | Standard Deviation 15.17 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C31D1 | 1.7 mm Hg | Standard Deviation 10.52 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C32D1 | 3.8 mm Hg | Standard Deviation 14.22 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C33D1 | 0.2 mm Hg | Standard Deviation 15.02 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C34D1 | 2.5 mm Hg | Standard Deviation 15.97 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C35D1 | 2.9 mm Hg | Standard Deviation 12.89 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C36D1 | 5.3 mm Hg | Standard Deviation 19.01 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C37D1 | 2.7 mm Hg | Standard Deviation 16.02 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C38D1 | 4.9 mm Hg | Standard Deviation 14.66 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C39D1 | 4.3 mm Hg | Standard Deviation 15.83 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C40D1 | 3.8 mm Hg | Standard Deviation 12.86 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C41D1 | 3.7 mm Hg | Standard Deviation 14.22 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C42D1 | 0.9 mm Hg | Standard Deviation 15.02 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C43D1 | -1.9 mm Hg | Standard Deviation 11.49 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C44D1 | 0.8 mm Hg | Standard Deviation 5.7 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C45D1 | -3.5 mm Hg | Standard Deviation 14.18 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C46D1 | -3.4 mm Hg | Standard Deviation 10.65 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C47D1 | 2.8 mm Hg | Standard Deviation 13.29 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C48D1 | -1.3 mm Hg | Standard Deviation 9.5 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C49D1 | 7.0 mm Hg | Standard Deviation 14.11 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C50D1 | 0.9 mm Hg | Standard Deviation 10.06 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C51D1 | 1.4 mm Hg | Standard Deviation 10.01 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C52D1 | 5.4 mm Hg | Standard Deviation 17.74 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C53D1 | 1.5 mm Hg | Standard Deviation 17.94 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C54D1 | 0.0 mm Hg | Standard Deviation 18.36 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C55D1 | 6.0 mm Hg | — |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | C56D1 | 3.0 mm Hg | — |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | End of Treatment | 3.5 mm Hg | Standard Deviation 18.94 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | Follow-up Day 30 | 1.7 mm Hg | Standard Deviation 18.67 |
| Axitinib + Avelumab | Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure | Follow-up Day 60 | 15.3 mm Hg | Standard Deviation 15.68 |
Secondary
Cmax for Avelumab
Cmax for avelumab on Cycle 1 Day (C1D1) and C1D4 were reported. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time frame: Predose, 1 hour, and 168 hours post dose on Cycle 1 Day 1; predose and 1 hour post dose on Cycle 4 Day 1
Population: The population for this outcome measure included all enrolled participants who received at least 1 dose of avelumab or axitinib and who had at least 1 of the pharmacokinetic (PK) parameters of interest of either study drug.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Axitinib + Avelumab With Lead-in | Cmax for Avelumab | C1D1 | 233.4 ug/mL | Geometric Coefficient of Variation 27 |
| Axitinib + Avelumab With Lead-in | Cmax for Avelumab | C4D1 | 278.0 ug/mL | Geometric Coefficient of Variation 60 |
Secondary
Duration of Response (DR) Based on RECIST Version 1.1
DR was defined as the time from the first documentation of objective tumor response (CR or PR) that was subsequently confirmed to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \<10 mm). PR was defined as \>= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must have been assessed. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time frame: Cycle 1 Day 1 up to 30 months after the first dose
Population: The population for this outcome measure included all participants who received at least 1 dose of study drug (axitinib or avelumab), all participants who were randomized independent of whether they had received a dose of study drug, and all participants who had achieved confirmed CR or PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Axitinib + Avelumab With Lead-in | Duration of Response (DR) Based on RECIST Version 1.1 | NA months |
| Axitinib + Avelumab | Duration of Response (DR) Based on RECIST Version 1.1 | NA months |
Secondary
Maximum Observed Plasma Concentration (Cmax) for Axitinib When Dosed Alone and in Combination With Avelumab
Cmax for axitinib when dosed alone on Lead-in Day 7 and in combination with avelumab on Cycle 4 Day 1 for Axitinib + Avelumab with Lead-in Arm. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time frame: Predose, 1, 2, 3, 4, 6, and 8 hours post dose on Lead-in Day 7 and Cycle 4 Day 1
Population: The population for this outcome measure included all enrolled participants who received at least 1 dose of avelumab or axitinib and who had at least 1 of the pharmacokinetic (PK) parameters of interest of either study drug.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Axitinib + Avelumab With Lead-in | Maximum Observed Plasma Concentration (Cmax) for Axitinib When Dosed Alone and in Combination With Avelumab | Lean-in Day 7 | 23.1947 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 178 |
| Axitinib + Avelumab With Lead-in | Maximum Observed Plasma Concentration (Cmax) for Axitinib When Dosed Alone and in Combination With Avelumab | Cycle 4 Day 1 | 16.5806 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 254 |
Secondary
Number of Participants Achieving Disease Control (DC) Based on RECIST Version 1.1
DC was defined as OR (CR or PR) or stable disease (SD) per RECIST v1.1 from the start date until the first documentation of objective disease progression or death due to any cause. SD was defined as not qualifying for CR, PR, or progression (PD). PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \<10 mm). PR was defined as \>= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must have been assessed. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time frame: Cycle 1 Day 1 up to 30 months after the first dose
Population: The population for this outcome measure included all participants who received at least 1 dose of study drug (axitinib or avelumab) and all participants who were randomized independent of whether they had received a dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Axitinib + Avelumab With Lead-in | Number of Participants Achieving Disease Control (DC) Based on RECIST Version 1.1 | 15 Participants |
| Axitinib + Avelumab | Number of Participants Achieving Disease Control (DC) Based on RECIST Version 1.1 | 28 Participants |
Secondary
Number of Participants Achieving Objective Response (OR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Confirmed OR was defined as complete response (CR) or partial response (PR) according to RECIST v1.1 from the start date until disease progression or death due to any cause. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \<10 mm). PR was defined as \>= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must have been assessed. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time frame: Cycle 1 Day 1 up to 30 months after the first dose
Population: The population for this outcome measure included all participants who received at least 1 dose of study drug (axitinib or avelumab) and all participants who were randomized independent of whether they had received a dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Axitinib + Avelumab With Lead-in | Number of Participants Achieving Objective Response (OR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | CR | 2 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants Achieving Objective Response (OR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | PR | 8 Participants |
| Axitinib + Avelumab | Number of Participants Achieving Objective Response (OR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | CR | 2 Participants |
| Axitinib + Avelumab | Number of Participants Achieving Objective Response (OR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | PR | 21 Participants |
Secondary
Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs)
Adverse event (AE)=any untoward medical occurrence in participant who received study treatment without regard to causality. TEAE=event between first dose of study treatment and up to 30 days after last dose that were absent before treatment or worsened relative to pretreatment state. Serious AE (SAE)=AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience; persistent or significant disability/incapacity; congenital anomaly. AEs were graded by worst National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 severity grade. Grade 3 event=unacceptable or intolerable event, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 event caused participant to be in imminent danger of death. Grade 5 event=death related to AE. The results reflect data available on cutoff of LPLV (04 Mar 2021).
Time frame: Baseline up to 30 days after the last dose of study treatment (maximum of 259.7 weeks)
Population: The population for this outcome measure included all enrolled participants who received at least 1 dose of avelumab or axitinib.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Axitinib + Avelumab With Lead-in | Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) | Participants with TEAEs | 16 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) | Participants with Grade >=3 TEAEs | 13 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) | Participants with SAEs | 6 Participants |
| Axitinib + Avelumab | Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) | Participants with TEAEs | 39 Participants |
| Axitinib + Avelumab | Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) | Participants with Grade >=3 TEAEs | 30 Participants |
| Axitinib + Avelumab | Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) | Participants with SAEs | 18 Participants |
Secondary
Number of Participants With Anti-drug Antibody (ADA) Against Avelumab When Combined With Axitinib by Never and Ever Positive Status
Whole blood specimens were collected at the designated times (Day 1 of Cycles 1-4, 6, and 8, then every 12 weeks until Cycle 50, and Follow-up Day 30) to provide serum for evaluation of avelumab immunogenicity. Human serum ADA specimens were analyzed for the presence or absence of anti-avelumab antibodies with quasi-quantitative enzyme-linked immunosorbent assay, following a tiered approach using screening, confirmation and titer/quantitation. ADA serum specimens were screened at tier 1. In the event that there were no positive specimens, no further analyses were to be conducted. If positive specimens were identified, these specimens were further tested with the confirmatory assay to confirm as positive. Number of participants with ADA positive at baseline, ADA never-positive, ADA ever-positive, treatment-boosted ADA, treatment-induced ADA, transient ADA response, or persistent ADA response from baseline up to 2 years. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time frame: Pre-dose on Day 1 of Cycles 1-4, 6, 8, then every 12 weeks thereafter until Cycle 50, and on Follow-up Day 30 (maximum of 2 years)
Population: The analysis population (ie, Number of Participants Analyzed)=number of participants (#p) received at least 1 dose of study drug and with at least 1 ADA sample collected. Number Analyzed =Number of Participants Analyzed for ADA\_p and ADA\_n; = #p with valid baseline ADA result for ADA\_bp; = #p with valid baseline and at least 1 valid post-baseline ADA results for Tb\_ADA; = #p with at least 1 valid post-baseline ADA result and without positive baseline ADA result for Ti\_ADA, t\_ADA, and p\_ADA.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Axitinib + Avelumab With Lead-in | Number of Participants With Anti-drug Antibody (ADA) Against Avelumab When Combined With Axitinib by Never and Ever Positive Status | ADA ever-positive (ADA_p) | 3 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Anti-drug Antibody (ADA) Against Avelumab When Combined With Axitinib by Never and Ever Positive Status | Treatment-induced ADA (Ti_ADA) | 1 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Anti-drug Antibody (ADA) Against Avelumab When Combined With Axitinib by Never and Ever Positive Status | ADA never-positive (ADA_n) | 12 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Anti-drug Antibody (ADA) Against Avelumab When Combined With Axitinib by Never and Ever Positive Status | Transient ADA response (t_ADA) | 0 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Anti-drug Antibody (ADA) Against Avelumab When Combined With Axitinib by Never and Ever Positive Status | Treatment-boosted ADA (Tb_ADA) | 0 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Anti-drug Antibody (ADA) Against Avelumab When Combined With Axitinib by Never and Ever Positive Status | Persistent ADA response (p_ADA) | 1 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Anti-drug Antibody (ADA) Against Avelumab When Combined With Axitinib by Never and Ever Positive Status | ADA positive at baseline (ADA_bp) | 2 Participants |
| Axitinib + Avelumab | Number of Participants With Anti-drug Antibody (ADA) Against Avelumab When Combined With Axitinib by Never and Ever Positive Status | Persistent ADA response (p_ADA) | 3 Participants |
| Axitinib + Avelumab | Number of Participants With Anti-drug Antibody (ADA) Against Avelumab When Combined With Axitinib by Never and Ever Positive Status | ADA positive at baseline (ADA_bp) | 0 Participants |
| Axitinib + Avelumab | Number of Participants With Anti-drug Antibody (ADA) Against Avelumab When Combined With Axitinib by Never and Ever Positive Status | ADA never-positive (ADA_n) | 31 Participants |
| Axitinib + Avelumab | Number of Participants With Anti-drug Antibody (ADA) Against Avelumab When Combined With Axitinib by Never and Ever Positive Status | ADA ever-positive (ADA_p) | 8 Participants |
| Axitinib + Avelumab | Number of Participants With Anti-drug Antibody (ADA) Against Avelumab When Combined With Axitinib by Never and Ever Positive Status | Treatment-boosted ADA (Tb_ADA) | 0 Participants |
| Axitinib + Avelumab | Number of Participants With Anti-drug Antibody (ADA) Against Avelumab When Combined With Axitinib by Never and Ever Positive Status | Treatment-induced ADA (Ti_ADA) | 8 Participants |
| Axitinib + Avelumab | Number of Participants With Anti-drug Antibody (ADA) Against Avelumab When Combined With Axitinib by Never and Ever Positive Status | Transient ADA response (t_ADA) | 5 Participants |
Secondary
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry
Laboratory abnormalities (chemistry) reported included creatinine increased, serum amylase increased, lipase increased, alanine aminotransferase (ALT) increased, aspartate aminotransferase (AST) increased, blood bilirubin increased, creatine kinase increased, hypoglycemia, and hyperglycemia. Grade 1=mild transient reaction; infusion interruption not indicated; intervention not indicated. Grade 2=therapy or infusion interruption indicated but responds promptly to symptomatic treatment; prophylactic medications indicated for \<=24 hours. Grade 3=prolonged; recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae. Grade 4=life threatening consequences; urgent intervention indicated. Grade 5=death. The results reflect data available on cutoff of LPLV (04 Mar 2021).
Time frame: Baseline up to 30 days after the last dose of study treatment and 1 day before the start day of new anti-cancer drug therapy (maximum of 259.7 weeks)
Population: The population for this outcome measure included all enrolled participants who received at least 1 dose of avelumab or axitinib.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Axitinib + Avelumab With Lead-in | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=1 ALT increased | 8 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=3 AST increased | 1 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=3 serum amylase increased | 4 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=3 hypoglycemia | 0 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=3 ALT increased | 2 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=1 hyperglycemia | 5 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=1 blood bilirubin increased | 2 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=1 serum amylase increased | 11 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=3 blood bilirubin increased | 0 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=3 lipase increased | 5 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=1 creatine kinase increased | 6 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=1 lipase increased | 9 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=3 creatine kinase increased | 1 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=3 creatinine increased | 0 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=1 hypoglycemia | 4 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=1 AST increased | 10 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=3 hyperglycemia | 2 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=1 creatinine increased | 16 Participants |
| Axitinib + Avelumab | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=3 hyperglycemia | 1 Participants |
| Axitinib + Avelumab | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=1 creatinine increased | 37 Participants |
| Axitinib + Avelumab | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=3 creatinine increased | 0 Participants |
| Axitinib + Avelumab | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=1 serum amylase increased | 16 Participants |
| Axitinib + Avelumab | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=3 serum amylase increased | 3 Participants |
| Axitinib + Avelumab | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=1 lipase increased | 16 Participants |
| Axitinib + Avelumab | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=1 ALT increased | 20 Participants |
| Axitinib + Avelumab | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=3 ALT increased | 2 Participants |
| Axitinib + Avelumab | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=3 lipase increased | 8 Participants |
| Axitinib + Avelumab | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=1 hypoglycemia | 4 Participants |
| Axitinib + Avelumab | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=1 AST increased | 21 Participants |
| Axitinib + Avelumab | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=3 AST increased | 1 Participants |
| Axitinib + Avelumab | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=3 hypoglycemia | 0 Participants |
| Axitinib + Avelumab | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=1 blood bilirubin increased | 7 Participants |
| Axitinib + Avelumab | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=3 blood bilirubin increased | 0 Participants |
| Axitinib + Avelumab | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=1 creatine kinase increased | 15 Participants |
| Axitinib + Avelumab | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=3 creatine kinase increased | 0 Participants |
| Axitinib + Avelumab | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry | Participants with Grade >=1 hyperglycemia | 13 Participants |
Secondary
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology
Laboratory abnormalities (hematology) reported included anemia, platelet count decreased, lymphocyte count decreased, and neutrophil count decreased. Grade 1=mild transient reaction; infusion interruption not indicated; intervention not indicated. Grade 2=therapy or infusion interruption indicated but responds promptly to symptomatic treatment; prophylactic medications indicated for \<=24 hours. Grade 3=prolonged; recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae. Grade 4=life threatening consequences; urgent intervention indicated. Grade 5=death. The results reflect data available on cutoff of LPLV (04 Mar 2021).
Time frame: Baseline up to 30 days after the last dose of study treatment and 1 day before the start day of new anti-cancer drug therapy (maximum of 259.7 weeks)
Population: The population for this outcome measure included all enrolled participants who received at least 1 dose of avelumab or axitinib.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Axitinib + Avelumab With Lead-in | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology | Participants with Grade >=1 anemia | 8 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology | Participants with Grade >=3 anemia | 0 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology | Participants with Grade >=1 platelet count decreased | 4 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology | Participants with Grade >=3 platelet count decreased | 0 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology | Participants with Grade >=1 lymphocyte count decreased | 10 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology | Participants with Grade >=3 lymphocyte count decreased | 1 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology | Participants with Grade >=1 neutrophil count decreased | 1 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology | Participants with Grade >=3 neutrophil count decreased | 0 Participants |
| Axitinib + Avelumab | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology | Participants with Grade >=3 neutrophil count decreased | 0 Participants |
| Axitinib + Avelumab | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology | Participants with Grade >=1 anemia | 24 Participants |
| Axitinib + Avelumab | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology | Participants with Grade >=1 lymphocyte count decreased | 16 Participants |
| Axitinib + Avelumab | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology | Participants with Grade >=3 anemia | 2 Participants |
| Axitinib + Avelumab | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology | Participants with Grade >=1 neutrophil count decreased | 4 Participants |
| Axitinib + Avelumab | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology | Participants with Grade >=1 platelet count decreased | 11 Participants |
| Axitinib + Avelumab | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology | Participants with Grade >=3 lymphocyte count decreased | 3 Participants |
| Axitinib + Avelumab | Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology | Participants with Grade >=3 platelet count decreased | 0 Participants |
Secondary
Number of Participants With Their Target Programmed Death-Ligand (PD-L1) Status at Baseline
Number of participants with PD-L1 positive (PD-L1 \>=1%) status in immune cell (IC), tumor cell (TC), or both IC and TC. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time frame: Baseline
Population: The population for this outcome measure included all enrolled participants who had at least 1 screening biomarker assessment and who received at least 1 dose of avelumab or axitinib.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Axitinib + Avelumab With Lead-in | Number of Participants With Their Target Programmed Death-Ligand (PD-L1) Status at Baseline | IC | 11 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Their Target Programmed Death-Ligand (PD-L1) Status at Baseline | TC | 3 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Their Target Programmed Death-Ligand (PD-L1) Status at Baseline | IC+TC | 11 Participants |
| Axitinib + Avelumab | Number of Participants With Their Target Programmed Death-Ligand (PD-L1) Status at Baseline | IC | 30 Participants |
| Axitinib + Avelumab | Number of Participants With Their Target Programmed Death-Ligand (PD-L1) Status at Baseline | TC | 15 Participants |
| Axitinib + Avelumab | Number of Participants With Their Target Programmed Death-Ligand (PD-L1) Status at Baseline | IC+TC | 32 Participants |
Secondary
Number of Participants With Treatment-related TEAEs
Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. TEAE=event between first dose of study treatment and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience; persistent or significant disability/incapacity; congenital anomaly. AEs were graded by worst NCI CTCAE v4.03 severity grade. Grade 3 events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 events caused participant to be in imminent danger of death. Grade 5 events=death related to an AE. Treatment-related AEs and SAEs were determined by the investigator. The results reflect data available on cutoff of LPLV (04 Mar 2021).
Time frame: Baseline up to 30 days after the last dose of study treatment (maximum of 259.7 weeks)
Population: The population for this outcome measure included all enrolled participants who received at least 1 dose of avelumab or axitinib.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Axitinib + Avelumab With Lead-in | Number of Participants With Treatment-related TEAEs | Participants with treatment-related TEAEs | 15 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Treatment-related TEAEs | Participants with Grade >=3 treatment-related TEAEs | 11 Participants |
| Axitinib + Avelumab With Lead-in | Number of Participants With Treatment-related TEAEs | Participants with treatment-related SAEs | 3 Participants |
| Axitinib + Avelumab | Number of Participants With Treatment-related TEAEs | Participants with treatment-related TEAEs | 39 Participants |
| Axitinib + Avelumab | Number of Participants With Treatment-related TEAEs | Participants with Grade >=3 treatment-related TEAEs | 23 Participants |
| Axitinib + Avelumab | Number of Participants With Treatment-related TEAEs | Participants with treatment-related SAEs | 10 Participants |
Secondary
Overall Survival (OS)
OS was defined as the time from the start date to the date of death due to any cause. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time frame: Cycle 1 Day 1 up to 30 months after the first dose
Population: The population for this outcome measure included all participants who received at least 1 dose of study drug (axitinib or avelumab) and all participants who were randomized independent of whether they had received a dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Axitinib + Avelumab With Lead-in | Overall Survival (OS) | NA months |
| Axitinib + Avelumab | Overall Survival (OS) | NA months |
Secondary
Predose Concentration During Multiple Dosing (Ctrough) for Avelumab
Ctrough was directly observed from data. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time frame: Predose on Day 1 of Cycles 1, 2, 3, 4, 6, 8, 14, 20, 26, 32, 38, 44, and 50
Population: The population for this outcome measure included all enrolled participants who received at least 1 dose of avelumab or axitinib and who had at least 1 of the pharmacokinetic (PK) parameters of interest of either study drug.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Axitinib + Avelumab With Lead-in | Predose Concentration During Multiple Dosing (Ctrough) for Avelumab | Cycle 1 Day 1 (C1D1) | 1.0 microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 181 |
| Axitinib + Avelumab With Lead-in | Predose Concentration During Multiple Dosing (Ctrough) for Avelumab | C2D1 | 20.3 microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 82 |
| Axitinib + Avelumab With Lead-in | Predose Concentration During Multiple Dosing (Ctrough) for Avelumab | C3D1 | 23.9 microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 151 |
| Axitinib + Avelumab With Lead-in | Predose Concentration During Multiple Dosing (Ctrough) for Avelumab | C4D1 | 23.4 microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 103 |
| Axitinib + Avelumab With Lead-in | Predose Concentration During Multiple Dosing (Ctrough) for Avelumab | C6D1 | 26.3 microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 134 |
| Axitinib + Avelumab With Lead-in | Predose Concentration During Multiple Dosing (Ctrough) for Avelumab | C8D1 | 28.3 microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 106 |
| Axitinib + Avelumab With Lead-in | Predose Concentration During Multiple Dosing (Ctrough) for Avelumab | C14D1 | 36.1 microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 59 |
| Axitinib + Avelumab With Lead-in | Predose Concentration During Multiple Dosing (Ctrough) for Avelumab | C20D1 | 41.0 microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 60 |
| Axitinib + Avelumab With Lead-in | Predose Concentration During Multiple Dosing (Ctrough) for Avelumab | C26D1 | 38.4 microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 77 |
| Axitinib + Avelumab With Lead-in | Predose Concentration During Multiple Dosing (Ctrough) for Avelumab | C32D1 | 40.8 microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 72 |
| Axitinib + Avelumab With Lead-in | Predose Concentration During Multiple Dosing (Ctrough) for Avelumab | C38D1 | 44.5 microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 68 |
| Axitinib + Avelumab With Lead-in | Predose Concentration During Multiple Dosing (Ctrough) for Avelumab | C44D1 | 67.5 microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 52 |
| Axitinib + Avelumab With Lead-in | Predose Concentration During Multiple Dosing (Ctrough) for Avelumab | C50D1 | 40.5 microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 121 |
Secondary
Progression-free Survival (PFS)
PFS was defined as defined as the time from the start date to the date of the first documentation of objective progression of disease (PD) or death due to any cause, whichever occurred first. PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm. All target lesions must have been assessed. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time frame: Cycle 1 Day 1 up to 30 months after the first dose
Population: The population for this outcome measure included all participants who received at least 1 dose of study drug (axitinib or avelumab) and all participants who were randomized independent of whether they had received a dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Axitinib + Avelumab With Lead-in | Progression-free Survival (PFS) | 19.2 months |
| Axitinib + Avelumab | Progression-free Survival (PFS) | 7.6 months |
Secondary
Terminal Half-Life (t1/2) for Axitinib When Dosed Alone and in Combination With Avelumab
t1/2 was calculated by Log e(2)/kel. kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration time-curve. Only those data points judged to describe the terminal log linear decline were used in the regression. t1/2 for Axitinib when dosed alone on Lead-in Day 7 and in combination with avelumab on Cycle 4 Day 1 for Axitinib + Avelumab with Lead-in Arm was reported. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time frame: Predose, 1, 2, 3, 4, 6, and 8 hours post dose on Lead-in Day 7 and Cycle 4 Day 1
Population: The population for this outcome measure included all enrolled participants who received at least 1 dose of avelumab or axitinib and who had at least 1 of the pharmacokinetic (PK) parameters of interest of either study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Axitinib + Avelumab With Lead-in | Terminal Half-Life (t1/2) for Axitinib When Dosed Alone and in Combination With Avelumab | Lean-in Day 7 | 2.755 hrs | Standard Deviation 1.5417 |
| Axitinib + Avelumab With Lead-in | Terminal Half-Life (t1/2) for Axitinib When Dosed Alone and in Combination With Avelumab | Cycle 4 Day 1 | 3.252 hrs | Standard Deviation 1.3389 |
Secondary
Time for Cmax (Tmax) for Axitinib When Dosed Alone and in Combination With Avelumab
Tmax for axitinib when dosed alone on Lead-in Day 7 and in combination with avelumab on Cycle 4 Day 1 for Axitinib + Avelumab with Lead-in Arm. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time frame: Predose, 1, 2, 3, 4, 6, and 8 hours post dose on Lead-in Day 7 and Cycle 4 Day 1
Population: The population for this outcome measure included all enrolled participants who received at least 1 dose of avelumab or axitinib and who had at least 1 of the pharmacokinetic (PK) parameters of interest of either study drug.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Axitinib + Avelumab With Lead-in | Time for Cmax (Tmax) for Axitinib When Dosed Alone and in Combination With Avelumab | Lean-in Day 7 | 2.0900 hours (hrs) |
| Axitinib + Avelumab With Lead-in | Time for Cmax (Tmax) for Axitinib When Dosed Alone and in Combination With Avelumab | Cycle 4 Day 1 | 1.9850 hours (hrs) |
Secondary
Time to Tumor Response (TTR) Based on RECIST Version 1.1
TTR was defined as the time from start date to the first documentation of objective tumor response (CR or PR) that was subsequently confirmed. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \<10 mm). PR was defined as \>= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must have been assessed. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time frame: Cycle 1 Day 1 up to 30 months after the first dose
Population: The population for this outcome measure included all participants who received at least 1 dose of study drug (axitinib or avelumab), all participants who were randomized independent of whether they had received a dose of study drug, and all participants who had achieved confirmed CR or PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Axitinib + Avelumab With Lead-in | Time to Tumor Response (TTR) Based on RECIST Version 1.1 | 1.6 months |
| Axitinib + Avelumab | Time to Tumor Response (TTR) Based on RECIST Version 1.1 | 1.4 months |