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A Study Of Avelumab In Combination With Axitinib In Advanced Renal Cell Cancer (JAVELIN Renal 100)

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT02493751
Collaborator
(none)
55
Enrollment
21
Locations
1
Arm
64.3
Actual Duration (Months)
2.6
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Avelumab (MSB0010718C)
  • Drug: Axitinib (AG-013736)
 Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
55 participants
Allocation:
N/A
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A PHASE 1B, OPEN-LABEL, DOSE-FINDING STUDY TO EVALUATE SAFETY, PHARMACOKINETICS AND PHARMACODYNAMICS OF AVELUMAB (MSB0010718C) IN COMBINATION WITH AXITINIB (AG-013736) IN PATIENTS WITH PREVIOUSLY UNTREATED ADVANCED RENAL CELL CANCER
Actual Study Start Date :
Oct 26, 2015
Actual Primary Completion Date :
Apr 3, 2018
Actual Study Completion Date :
Mar 4, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Dose finding phase and dose expansion phase.

To test the maximum tolerated dose of avelumab (MSB0010718C) in combination with axitinib (AG-013736)

Drug: Avelumab (MSB0010718C)
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.

Drug: Axitinib (AG-013736)
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.

Outcome Measures

Primary Outcome Measures

  1. 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 Outcome Measures

  1. 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).

  2. 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).

  3. 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).

  4. 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).

  5. 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).

  6. 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).

  7. 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).

  8. 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).

  9. 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).

  10. 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).

  11. 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).

  12. 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).

  13. 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).

  14. 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).

  15. 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).

  16. 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).

  17. 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).

  18. 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).

  19. 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).

  20. 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).

  21. 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).

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts 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).

Contacts and Locations

Locations

Site City State Country Postal Code
1 Scottsdale Healthcare Hospitals d/b/a HonorHealth Scottsdale Arizona United States 85258
2 Georgetown University Medical Center Washington District of Columbia United States 20007
3 Brigham & Women's Hospital Boston Massachusetts United States 02115
4 Beth Israel Deaconess Medical Center Boston Massachusetts United States 02215
5 Dana Farber Cancer Institute Boston Massachusetts United States 02215
6 Laura & Isaac Perlmutter Cancer Center At NYU Langone New York New York United States 10016
7 NYU Langone Medical Center New York New York United States 10016
8 Cleveland Clinic Taussig Cancer Center Cleveland Ohio United States 44106
9 Cleveland Clinic Cleveland Ohio United States 44195
10 Henry Joyce Cancer Clinic Nashville Tennessee United States 37232-5310
11 University of Utah, Huntsman Cancer Hospital Salt Lake City Utah United States 84112
12 University of Utah, Huntsman Cancer Institute Salt Lake City Utah United States 84112
13 Niigata University Medical & Dental Hospital Chuo-ku, Niigata Niigata Japan 951-8520
14 Kindai University Hospital Osakasayama Osaka Japan 589-8511
15 Keio University Hospital Shinjuku-ku Tokyo Japan 160-8582
16 Mount Vernon Cancer Center, East and North Herts. NHS Trust London Middlesex United Kingdom HA6 2RN
17 St Helier Hospital Carshalton Surrey United Kingdom SM5 1AA
18 St. Bartholomew's Hospital London United Kingdom EC1A 7BE
19 The Royal Marsden NHS Foundation Trust London United Kingdom SW3 6JJ
20 The Christie NHS Foundation Trust Manchester United Kingdom M20 4BX
21 The Royal Marsden NHS Foundation Trust Sutton United Kingdom SM2 5PT

Sponsors and Collaborators

  • Pfizer

Investigators

  • Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT02493751
Other Study ID Numbers:
  • B9991002
  • 2015-001137-25
  • Javelin Renal 100
First Posted:
Jul 9, 2015
Last Update Posted:
Feb 18, 2022
Last Verified:
Dec 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Keywords provided by Pfizer
Cancer, renal cell cancer, kidney disease, kidney neoplasms, axitinib
Additional relevant MeSH terms:
Carcinoma, Renal Cell
Avelumab
Axitinib

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail 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).
Arm/Group Title Axitinib + Avelumab With Lead-in Axitinib + Avelumab
Arm/Group Description 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). 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).
Period Title: Overall Study
STARTED 16 39
COMPLETED 0 0
NOT COMPLETED 16 39

Baseline Characteristics

Arm/Group Title Axitinib + Avelumab With Lead-in Axitinib + Avelumab Total
Arm/Group Description 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). 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). Total of all reporting groups
Overall Participants 16 39 55
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
60.0
(8.45)
60.5
(8.89)
60.3
(8.69)
Sex: Female, Male (Count of Participants)
Female
2
12.5%
11
28.2%
13
23.6%
Male
14
87.5%
28
71.8%
42
76.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
0
0%
0
0%
0
0%
Not Hispanic or Latino
16
100%
35
89.7%
51
92.7%
Unknown or Not Reported
0
0%
4
10.3%
4
7.3%
Race/Ethnicity, Customized (Count of Participants)
Black or African American
1
6.3%
2
5.1%
3
5.5%
American Indian or Alaska Native
0
0%
0
0%
0
0%
Asian
0
0%
6
15.4%
6
10.9%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
White
15
93.8%
29
74.4%
44
80%
Other
0
0%
1
2.6%
1
1.8%
Unknown
0
0%
1
2.6%
1
1.8%

Outcome Measures

1. Primary Outcome
Title Number of Participants With Dose Limiting Toxicities (DLTs)
Description 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])

Outcome Measure Data

Analysis Population Description
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/Group Title Axitinib + Avelumab With Lead-in
Arm/Group Description 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).
Measure Participants 6
Count of Participants [Participants]
1
6.3%
2. Secondary Outcome
Title Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs)
Description 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)

Outcome Measure Data

Analysis Population Description
The population for this outcome measure included all enrolled participants who received at least 1 dose of avelumab or axitinib.
Arm/Group Title Axitinib + Avelumab With Lead-in Axitinib + Avelumab
Arm/Group Description 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). 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).
Measure Participants 16 39
Participants with TEAEs
16
100%
39
100%
Participants with Grade >=3 TEAEs
13
81.3%
30
76.9%
Participants with SAEs
6
37.5%
18
46.2%
3. Secondary Outcome
Title Number of Participants With Treatment-related TEAEs
Description 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)

Outcome Measure Data

Analysis Population Description
The population for this outcome measure included all enrolled participants who received at least 1 dose of avelumab or axitinib.
Arm/Group Title Axitinib + Avelumab With Lead-in Axitinib + Avelumab
Arm/Group Description 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). 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).
Measure Participants 16 39
Participants with treatment-related TEAEs
15
93.8%
39
100%
Participants with Grade >=3 treatment-related TEAEs
11
68.8%
23
59%
Participants with treatment-related SAEs
3
18.8%
10
25.6%
4. Secondary Outcome
Title Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology
Description 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)

Outcome Measure Data

Analysis Population Description
The population for this outcome measure included all enrolled participants who received at least 1 dose of avelumab or axitinib.
Arm/Group Title Axitinib + Avelumab With Lead-in Axitinib + Avelumab
Arm/Group Description 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). 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).
Measure Participants 16 39
Participants with Grade >=1 anemia
8
50%
24
61.5%
Participants with Grade >=3 anemia
0
0%
2
5.1%
Participants with Grade >=1 platelet count decreased
4
25%
11
28.2%
Participants with Grade >=3 platelet count decreased
0
0%
0
0%
Participants with Grade >=1 lymphocyte count decreased
10
62.5%
16
41%
Participants with Grade >=3 lymphocyte count decreased
1
6.3%
3
7.7%
Participants with Grade >=1 neutrophil count decreased
1
6.3%
4
10.3%
Participants with Grade >=3 neutrophil count decreased
0
0%
0
0%
5. Secondary Outcome
Title Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry
Description 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)

Outcome Measure Data

Analysis Population Description
The population for this outcome measure included all enrolled participants who received at least 1 dose of avelumab or axitinib.
Arm/Group Title Axitinib + Avelumab With Lead-in Axitinib + Avelumab
Arm/Group Description 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). 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).
Measure Participants 16 39
Participants with Grade >=1 creatinine increased
16
100%
37
94.9%
Participants with Grade >=3 creatinine increased
0
0%
0
0%
Participants with Grade >=1 serum amylase increased
11
68.8%
16
41%
Participants with Grade >=3 serum amylase increased
4
25%
3
7.7%
Participants with Grade >=1 lipase increased
9
56.3%
16
41%
Participants with Grade >=3 lipase increased
5
31.3%
8
20.5%
Participants with Grade >=1 ALT increased
8
50%
20
51.3%
Participants with Grade >=3 ALT increased
2
12.5%
2
5.1%
Participants with Grade >=1 AST increased
10
62.5%
21
53.8%
Participants with Grade >=3 AST increased
1
6.3%
1
2.6%
Participants with Grade >=1 blood bilirubin increased
2
12.5%
7
17.9%
Participants with Grade >=3 blood bilirubin increased
0
0%
0
0%
Participants with Grade >=1 creatine kinase increased
6
37.5%
15
38.5%
Participants with Grade >=3 creatine kinase increased
1
6.3%
0
0%
Participants with Grade >=1 hypoglycemia
4
25%
4
10.3%
Participants with Grade >=3 hypoglycemia
0
0%
0
0%
Participants with Grade >=1 hyperglycemia
5
31.3%
13
33.3%
Participants with Grade >=3 hyperglycemia
2
12.5%
1
2.6%
6. Secondary Outcome
Title Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure
Description 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)

Outcome Measure Data

Analysis Population Description
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/Group Title Axitinib + Avelumab With Lead-in Axitinib + Avelumab
Arm/Group Description 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). 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).
Measure Participants 16 39
Lead-in Day 7
5.4
(9.32)
C1D1
4.1
(9.36)
C1D8
3.2
(12.80)
9.8
(11.81)
C2D1
3.4
(13.15)
10.1
(10.03)
C2D8
1.8
(10.01)
14.7
(5.03)
C3D1
6.1
(12.16)
10.2
(11.80)
C4D1
3.6
(10.34)
8.8
(9.60)
C5D1
4.8
(10.53)
6.9
(11.64)
C6D1
3.0
(9.84)
7.5
(11.76)
C7D1
4.8
(11.82)
7.5
(12.50)
C8D1
5.7
(10.76)
9.0
(10.86)
C9D1
3.9
(10.80)
10.0
(13.44)
C10D1
7.3
(9.80)
7.7
(8.97)
C11D1
7.4
(8.98)
7.5
(11.09)
C12D1
5.3
(8.20)
6.6
(12.07)
C13D1
6.0
(7.71)
10.5
(11.92)
C14D1
5.4
(10.87)
7.2
(14.04)
C15D1
6.9
(6.56)
7.6
(12.13)
C16D1
7.5
(10.33)
5.8
(13.57)
C17D1
6.2
(9.84)
6.4
(13.20)
C18D1
4.3
(8.45)
5.1
(12.22)
C19D1
6.3
(7.58)
5.5
(10.67)
C20D1
7.9
(6.71)
6.9
(11.69)
C21D1
8.9
(9.35)
6.6
(10.22)
C22D1
7.2
(9.34)
6.2
(11.96)
C23D1
9.2
(9.54)
4.5
(11.52)
C24D1
7.3
(8.42)
4.3
(12.91)
C25D1
3.1
(9.62)
6.0
(13.34)
C26D1
5.6
(9.65)
7.8
(12.33)
C27D1
4.5
(8.64)
6.2
(13.39)
C28D1
4.9
(7.53)
6.2
(13.35)
C29D1
5.4
(9.90)
7.1
(11.13)
C30D1
5.6
(8.53)
6.1
(13.32)
C31D1
4.8
(11.40)
6.7
(10.41)
C32D1
7.1
(11.06)
7.6
(13.52)
C33D1
5.5
(6.59)
3.6
(13.67)
C34D1
3.5
(13.67)
5.0
(15.71)
C35D1
7.2
(9.76)
8.1
(12.46)
C36D1
7.5
(9.40)
10.9
(11.31)
C37D1
9.9
(10.47)
7.6
(13.32)
C38D1
5.0
(8.92)
6.9
(12.73)
C39D1
6.6
(10.10)
7.9
(14.61)
C40D1
7.8
(10.75)
6.0
(13.08)
C41D1
6.6
(9.76)
8.4
(11.70)
C42D1
5.9
(9.35)
5.7
(13.64)
C43D1
13.0
(11.53)
2.5
(7.73)
C44D1
8.3
(11.04)
6.6
(10.08)
C45D1
8.1
(10.23)
5.4
(13.16)
C46D1
11.1
(11.27)
3.0
(14.03)
C47D1
8.4
(13.62)
1.1
(12.01)
C48D1
6.3
(9.75)
3.9
(13.37)
C49D1
9.4
(10.67)
11.8
(11.44)
C50D1
9.0
(9.27)
7.0
(11.53)
C51D1
9.3
(10.17)
4.3
(10.14)
C52D1
9.3
(11.60)
8.2
(11.48)
C53D1
15.4
(18.37)
2.0
(14.72)
C54D1
12.5
(7.42)
0.3
(12.66)
C55D1
16.0
(19.71)
-3.0
(NA)
C56D1
10.0
(13.74)
0.0
(NA)
C57D1
14.5
(12.15)
C58D1
16.5
(12.82)
C59D1
26.5
(9.19)
C60D1
22.5
(4.95)
C61D1
24.5
(4.95)
C62D1
22.0
(1.41)
End of Treatment
-1.6
(10.38)
2.5
(13.05)
Follow-up Day 30
-3.2
(8.41)
-2.9
(12.51)
Follow-up Day 60
-4.7
(10.26)
3.8
(8.33)
Follow-up Day 90
-2.0
(4.58)
1.3
(6.18)
7. Secondary Outcome
Title Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure
Description 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)

Outcome Measure Data

Analysis Population Description
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/Group Title Axitinib + Avelumab With Lead-in Axitinib + Avelumab
Arm/Group Description 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). 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).
Measure Participants 16 39
Lead-in Day 7
9.7
(13.44)
C1D1
11.0
(18.20)
C1D8
8.0
(18.94)
10.3
(16.12)
C2D1
4.6
(18.49)
11.2
(11.47)
C2D8
0.8
(15.63)
17.7
(6.66)
C3D1
9.9
(18.96)
8.7
(15.05)
C4D1
6.7
(15.61)
5.8
(11.73)
C5D1
6.2
(19.45)
6.7
(14.90)
C6D1
6.5
(15.05)
5.2
(13.34)
C7D1
10.2
(14.46)
6.1
(14.49)
C8D1
13.5
(12.07)
8.0
(15.14)
C9D1
11.4
(14.24)
10.2
(16.29)
C10D1
8.9
(16.83)
8.4
(15.69)
C11D1
7.8
(15.36)
7.2
(14.83)
C12D1
6.8
(11.27)
4.1
(14.29)
C13D1
7.3
(11.17)
8.6
(16.01)
C14D1
5.8
(15.49)
3.9
(17.66)
C15D1
7.3
(13.89)
7.3
(20.46)
C16D1
6.2
(13.46)
5.5
(16.80)
C17D1
7.3
(15.55)
3.5
(17.32)
C18D1
3.5
(14.67)
4.2
(15.07)
C19D1
5.8
(16.04)
2.6
(14.15)
C20D1
8.3
(9.67)
1.1
(12.20)
C21D1
5.0
(14.14)
3.1
(10.17)
C22D1
2.9
(14.53)
0.2
(14.31)
C23D1
9.3
(14.19)
1.5
(15.05)
C24D1
9.1
(12.55)
-0.1
(16.57)
C25D1
4.0
(12.78)
3.5
(15.28)
C26D1
2.8
(15.86)
3.4
(15.82)
C27D1
5.4
(14.74)
1.6
(16.13)
C28D1
7.8
(14.49)
2.1
(16.65)
C29D1
3.3
(14.28)
4.1
(11.82)
C30D1
6.4
(13.57)
2.9
(15.17)
C31D1
2.7
(13.14)
1.7
(10.52)
C32D1
8.6
(16.71)
3.8
(14.22)
C33D1
2.9
(16.07)
0.2
(15.02)
C34D1
2.8
(18.79)
2.5
(15.97)
C35D1
10.3
(13.47)
2.9
(12.89)
C36D1
9.0
(12.92)
5.3
(19.01)
C37D1
10.2
(11.48)
2.7
(16.02)
C38D1
8.3
(11.83)
4.9
(14.66)
C39D1
3.8
(13.33)
4.3
(15.83)
C40D1
10.9
(14.13)
3.8
(12.86)
C41D1
7.9
(16.74)
3.7
(14.22)
C42D1
11.6
(15.74)
0.9
(15.02)
C43D1
12.3
(13.20)
-1.9
(11.49)
C44D1
9.6
(21.41)
0.8
(5.70)
C45D1
9.1
(17.71)
-3.5
(14.18)
C46D1
6.1
(11.28)
-3.4
(10.65)
C47D1
6.6
(18.31)
2.8
(13.29)
C48D1
-0.1
(15.04)
-1.3
(9.50)
C49D1
5.4
(13.73)
7.0
(14.11)
C50D1
9.7
(10.50)
0.9
(10.06)
C51D1
13.5
(13.85)
1.4
(10.01)
C52D1
4.3
(16.17)
5.4
(17.74)
C53D1
17.0
(16.29)
1.5
(17.94)
C54D1
10.8
(14.20)
0.0
(18.36)
C55D1
15.8
(19.17)
6.0
(NA)
C56D1
8.5
(11.62)
3.0
(NA)
C57D1
11.5
(12.23)
C58D1
8.0
(17.45)
C59D1
21.5
(4.95)
C60D1
22.0
(19.80)
C61D1
20.0
(15.56)
C62D1
14.5
(13.44)
End of Treatment
11.3
(25.45)
3.5
(18.94)
Follow-up Day 30
15.0
(20.65)
1.7
(18.67)
Follow-up Day 60
16.0
(9.54)
15.3
(15.68)
Follow-up Day 90
20.7
(13.32)
9.3
(10.24)
8. Secondary Outcome
Title Change From Baseline in Vital Signs - Pulse Rate
Description 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)

Outcome Measure Data

Analysis Population Description
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/Group Title Axitinib + Avelumab With Lead-in Axitinib + Avelumab
Arm/Group Description 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). 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).
Measure Participants 16 39
Lean-in Day 7
-0.5
C1D1
-1.0
C1D8
-2.0
-2.0
C2D1
3.0
4.0
C2D8
8.0
2.0
C3D1
4.0
2.0
C4D1
1.5
4.0
C5D1
0.0
2.5
C6D1
-3.5
3.5
C7D1
1.0
1.0
C8D1
-6.5
-1.0
C9D1
-1.5
1.0
C10D1
-3.0
3.0
C11D1
-2.0
3.0
C12D1
-6.0
1.5
C13D1
-1.5
2.0
C14D1
1.5
5.0
C15D1
-4.5
-3.0
C16D1
-1.0
1.5
C17D1
-6.0
1.5
C18D1
0.0
3.0
C19D1
-1.0
-3.0
C20D1
2.0
1.0
C21D1
-1.5
2.5
C22D1
0.0
-6.0
C23D1
2.0
-3.0
C24D1
-3.5
0.0
C25D1
0.0
-4.5
C26D1
-4.0
-3.0
C27D1
1.5
0.5
C28D1
-8.5
0.5
C29D1
-6.0
-4.0
C30D1
-3.0
-2.0
C31D1
1.5
-3.5
C32D1
2.0
2.0
C33D1
-4.0
1.0
C34D1
-1.0
1.0
C35D1
-2.0
2.5
C36D1
1.0
0.0
C37D1
1.5
0.0
C38D1
-1.0
2.0
C39D1
0.0
-1.0
C40D1
-3.0
2.5
C41D1
-5.0
1.0
C42D1
-3.0
0.0
C43D1
4.5
1.0
C44D1
2.0
5.0
C45D1
2.5
9.5
C46D1
1.0
11.5
C47D1
5.0
5.5
C48D1
-3.0
4.5
C49D1
10.0
-0.5
C50D1
-2.0
4.0
C51D1
0.0
6.0
C52D1
0.5
3.0
C53D1
6.0
10.0
C54D1
2.5
1.0
C55D1
-6.5
5.0
C56D1
1.5
1.0
C57D1
-4.0
C58D1
4.0
C59D1
2.0
C60D1
1.5
C61D1
2.0
C62D1
9.0
End of Treatment
2.5
6.5
Follow-up Day 30
-1.0
-2.0
Follow-up Day 60
2.0
3.0
Follow-up Day 90
9.0
5.5
9. Secondary Outcome
Title Number of Participants Achieving Objective Response (OR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Description 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

Outcome Measure Data

Analysis Population Description
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/Group Title Axitinib + Avelumab With Lead-in Axitinib + Avelumab
Arm/Group Description 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). 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).
Measure Participants 16 39
CR
2
12.5%
2
5.1%
PR
8
50%
21
53.8%
10. Secondary Outcome
Title Number of Participants Achieving Disease Control (DC) Based on RECIST Version 1.1
Description 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

Outcome Measure Data

Analysis Population Description
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/Group Title Axitinib + Avelumab With Lead-in Axitinib + Avelumab
Arm/Group Description 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). 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).
Measure Participants 16 39
Count of Participants [Participants]
15
93.8%
28
71.8%
11. Secondary Outcome
Title Duration of Response (DR) Based on RECIST Version 1.1
Description 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

Outcome Measure Data

Analysis Population Description
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/Group Title Axitinib + Avelumab With Lead-in Axitinib + Avelumab
Arm/Group Description 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). 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).
Measure Participants 10 23
Median (95% Confidence Interval) [months]
NA
NA
12. Secondary Outcome
Title Progression-free Survival (PFS)
Description 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

Outcome Measure Data

Analysis Population Description
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/Group Title Axitinib + Avelumab With Lead-in Axitinib + Avelumab
Arm/Group Description 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). 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).
Measure Participants 16 39
Median (95% Confidence Interval) [months]
19.2
7.6
13. Secondary Outcome
Title Time to Tumor Response (TTR) Based on RECIST Version 1.1
Description 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

Outcome Measure Data

Analysis Population Description
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/Group Title Axitinib + Avelumab With Lead-in Axitinib + Avelumab
Arm/Group Description 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). 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).
Measure Participants 10 23
Median (Full Range) [months]
1.6
1.4
14. Secondary Outcome
Title Overall Survival (OS)
Description 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

Outcome Measure Data

Analysis Population Description
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/Group Title Axitinib + Avelumab With Lead-in Axitinib + Avelumab
Arm/Group Description 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). 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).
Measure Participants 16 39
Median (95% Confidence Interval) [months]
NA
NA
15. Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) for Axitinib When Dosed Alone and in Combination With Avelumab
Description 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

Outcome Measure Data

Analysis Population Description
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/Group Title Axitinib + Avelumab With Lead-in
Arm/Group Description 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).
Measure Participants 14
Lean-in Day 7
23.1947
(178)
Cycle 4 Day 1
16.5806
(254)
16. Secondary Outcome
Title Time for Cmax (Tmax) for Axitinib When Dosed Alone and in Combination With Avelumab
Description 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

Outcome Measure Data

Analysis Population Description
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/Group Title Axitinib + Avelumab With Lead-in
Arm/Group Description 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).
Measure Participants 14
Lean-in Day 7
2.0900
Cycle 4 Day 1
1.9850
17. Secondary Outcome
Title 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
Description 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

Outcome Measure Data

Analysis Population Description
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/Group Title Axitinib + Avelumab With Lead-in
Arm/Group Description 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).
Measure Participants 13
Lean-in Day 7
113.11
(206)
Cycle 4 Day 1
95.60
(162)
18. Secondary Outcome
Title Terminal Half-Life (t1/2) for Axitinib When Dosed Alone and in Combination With Avelumab
Description 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

Outcome Measure Data

Analysis Population Description
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/Group Title Axitinib + Avelumab With Lead-in
Arm/Group Description 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).
Measure Participants 10
Lean-in Day 7
2.755
(1.5417)
Cycle 4 Day 1
3.252
(1.3389)
19. Secondary Outcome
Title Predose Concentration During Multiple Dosing (Ctrough) for Avelumab
Description 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

Outcome Measure Data

Analysis Population Description
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/Group Title All Participants
Arm/Group Description 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 255.4 weeks).
Measure Participants 54
Cycle 1 Day 1 (C1D1)
1.0
(181)
C2D1
20.3
(82)
C3D1
23.9
(151)
C4D1
23.4
(103)
C6D1
26.3
(134)
C8D1
28.3
(106)
C14D1
36.1
(59)
C20D1
41.0
(60)
C26D1
38.4
(77)
C32D1
40.8
(72)
C38D1
44.5
(68)
C44D1
67.5
(52)
C50D1
40.5
(121)
20. Secondary Outcome
Title Cmax for Avelumab
Description 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

Outcome Measure Data

Analysis Population Description
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/Group Title All Participants
Arm/Group Description 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 255.4 weeks).
Measure Participants 54
C1D1
233.4
(27)
C4D1
278.0
(60)
21. Secondary Outcome
Title Number of Participants With Their Target Programmed Death-Ligand (PD-L1) Status at Baseline
Description 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

Outcome Measure Data

Analysis Population Description
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/Group Title Axitinib + Avelumab With Lead-in Axitinib + Avelumab
Arm/Group Description 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). 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).
Measure Participants 16 39
IC
11
68.8%
30
76.9%
TC
3
18.8%
15
38.5%
IC+TC
11
68.8%
32
82.1%
22. Secondary Outcome
Title Number of Participants With Anti-drug Antibody (ADA) Against Avelumab When Combined With Axitinib by Never and Ever Positive Status
Description 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)

Outcome Measure Data

Analysis Population Description
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/Group Title Axitinib + Avelumab With Lead-in Axitinib + Avelumab
Arm/Group Description 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). 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).
Measure Participants 15 39
ADA positive at baseline (ADA_bp)
2
12.5%
0
0%
ADA never-positive (ADA_n)
12
75%
31
79.5%
ADA ever-positive (ADA_p)
3
18.8%
8
20.5%
Treatment-boosted ADA (Tb_ADA)
0
0%
0
0%
Treatment-induced ADA (Ti_ADA)
1
6.3%
8
20.5%
Transient ADA response (t_ADA)
0
0%
5
12.8%
Persistent ADA response (p_ADA)
1
6.3%
3
7.7%

Adverse Events

Time Frame Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in)
Adverse Event Reporting Description Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Arm/Group Title Axitinib + Avelumab With Lead-in Axitinib + Avelumab
Arm/Group Description 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). 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).
All Cause Mortality
Axitinib + Avelumab With Lead-in Axitinib + Avelumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 6/16 (37.5%) 14/39 (35.9%)
Serious Adverse Events
Axitinib + Avelumab With Lead-in Axitinib + Avelumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 6/16 (37.5%) 18/39 (46.2%)
Blood and lymphatic system disorders
Anaemia 0/16 (0%) 1/39 (2.6%)
Neutropenia 0/16 (0%) 1/39 (2.6%)
Cardiac disorders
Myocarditis 1/16 (6.3%) 0/39 (0%)
Palpitations 0/16 (0%) 1/39 (2.6%)
Tachycardia 0/16 (0%) 1/39 (2.6%)
Endocrine disorders
Adrenal insufficiency 0/16 (0%) 1/39 (2.6%)
Gastrointestinal disorders
Diarrhoea 0/16 (0%) 1/39 (2.6%)
Nausea 1/16 (6.3%) 0/39 (0%)
Vomiting 1/16 (6.3%) 0/39 (0%)
Pancreatitis 0/16 (0%) 1/39 (2.6%)
General disorders
Adverse drug reaction 0/16 (0%) 1/39 (2.6%)
Disease progression 0/16 (0%) 2/39 (5.1%)
Pyrexia 0/16 (0%) 1/39 (2.6%)
Immune system disorders
Anaphylactic shock 0/16 (0%) 1/39 (2.6%)
Infections and infestations
Sepsis 0/16 (0%) 1/39 (2.6%)
Tooth abscess 1/16 (6.3%) 0/39 (0%)
Injury, poisoning and procedural complications
Infusion related reaction 0/16 (0%) 2/39 (5.1%)
Lower limb fracture 0/16 (0%) 1/39 (2.6%)
Rib fracture 0/16 (0%) 1/39 (2.6%)
Spinal fracture 0/16 (0%) 1/39 (2.6%)
Investigations
Alanine aminotransferase increased 1/16 (6.3%) 1/39 (2.6%)
Amylase increased 1/16 (6.3%) 0/39 (0%)
Aspartate aminotransferase increased 0/16 (0%) 1/39 (2.6%)
Lipase increased 1/16 (6.3%) 0/39 (0%)
Metabolism and nutrition disorders
Dehydration 0/16 (0%) 1/39 (2.6%)
Musculoskeletal and connective tissue disorders
Arthralgia 0/16 (0%) 1/39 (2.6%)
Muscular weakness 0/16 (0%) 1/39 (2.6%)
Nervous system disorders
Presyncope 0/16 (0%) 2/39 (5.1%)
Spinal cord compression 0/16 (0%) 2/39 (5.1%)
Psychiatric disorders
Substance-induced psychotic disorder 1/16 (6.3%) 0/39 (0%)
Renal and urinary disorders
Haematuria 0/16 (0%) 1/39 (2.6%)
Respiratory, thoracic and mediastinal disorders
Hypoxia 1/16 (6.3%) 1/39 (2.6%)
Pleural effusion 0/16 (0%) 1/39 (2.6%)
Pulmonary embolism 0/16 (0%) 1/39 (2.6%)
Skin and subcutaneous tissue disorders
Drug eruption 0/16 (0%) 1/39 (2.6%)
Vascular disorders
Haematoma 0/16 (0%) 2/39 (5.1%)
Haemorrhage 0/16 (0%) 1/39 (2.6%)
Venous thrombosis 0/16 (0%) 1/39 (2.6%)
Other (Not Including Serious) Adverse Events
Axitinib + Avelumab With Lead-in Axitinib + Avelumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 16/16 (100%) 39/39 (100%)
Blood and lymphatic system disorders
Anaemia 2/16 (12.5%) 5/39 (12.8%)
Leukocytosis 1/16 (6.3%) 0/39 (0%)
Leukopenia 1/16 (6.3%) 0/39 (0%)
Lymphopenia 1/16 (6.3%) 0/39 (0%)
Cardiac disorders
Palpitations 0/16 (0%) 2/39 (5.1%)
Sinus bradycardia 1/16 (6.3%) 1/39 (2.6%)
Sinus tachycardia 1/16 (6.3%) 1/39 (2.6%)
Ventricular arrhythmia 1/16 (6.3%) 0/39 (0%)
Ear and labyrinth disorders
Ear discomfort 0/16 (0%) 2/39 (5.1%)
Hypoacusis 2/16 (12.5%) 0/39 (0%)
Ear congestion 1/16 (6.3%) 0/39 (0%)
Endocrine disorders
Hyperthyroidism 2/16 (12.5%) 3/39 (7.7%)
Hypothyroidism 4/16 (25%) 11/39 (28.2%)
Eye disorders
Dry eye 1/16 (6.3%) 3/39 (7.7%)
Eye haemorrhage 1/16 (6.3%) 0/39 (0%)
Eyelid irritation 1/16 (6.3%) 0/39 (0%)
Vision blurred 1/16 (6.3%) 1/39 (2.6%)
Blepharitis 0/16 (0%) 2/39 (5.1%)
Gastrointestinal disorders
Abdominal discomfort 1/16 (6.3%) 1/39 (2.6%)
Abdominal pain 2/16 (12.5%) 6/39 (15.4%)
Abdominal pain upper 1/16 (6.3%) 2/39 (5.1%)
Anal haemorrhage 1/16 (6.3%) 1/39 (2.6%)
Constipation 8/16 (50%) 12/39 (30.8%)
Dental caries 1/16 (6.3%) 4/39 (10.3%)
Diarrhoea 13/16 (81.3%) 26/39 (66.7%)
Diverticulum 1/16 (6.3%) 1/39 (2.6%)
Dry mouth 3/16 (18.8%) 5/39 (12.8%)
Dyspepsia 1/16 (6.3%) 3/39 (7.7%)
Flatulence 2/16 (12.5%) 2/39 (5.1%)
Gastrooesophageal reflux disease 1/16 (6.3%) 5/39 (12.8%)
Gingival hypertrophy 1/16 (6.3%) 0/39 (0%)
Lip pain 1/16 (6.3%) 0/39 (0%)
Mouth ulceration 0/16 (0%) 2/39 (5.1%)
Nausea 7/16 (43.8%) 8/39 (20.5%)
Oral pain 1/16 (6.3%) 3/39 (7.7%)
Rectal haemorrhage 1/16 (6.3%) 1/39 (2.6%)
Stomatitis 4/16 (25%) 4/39 (10.3%)
Tongue discomfort 1/16 (6.3%) 0/39 (0%)
Toothache 1/16 (6.3%) 3/39 (7.7%)
Vomiting 4/16 (25%) 10/39 (25.6%)
Haemorrhoids 0/16 (0%) 2/39 (5.1%)
Hyperaesthesia teeth 1/16 (6.3%) 0/39 (0%)
Retching 1/16 (6.3%) 0/39 (0%)
Defaecation urgency 1/16 (6.3%) 0/39 (0%)
General disorders
Axillary pain 0/16 (0%) 2/39 (5.1%)
Chest discomfort 2/16 (12.5%) 1/39 (2.6%)
Chest pain 2/16 (12.5%) 0/39 (0%)
Chills 2/16 (12.5%) 7/39 (17.9%)
Fatigue 10/16 (62.5%) 20/39 (51.3%)
Feeling abnormal 1/16 (6.3%) 0/39 (0%)
Feeling cold 1/16 (6.3%) 1/39 (2.6%)
Gait disturbance 0/16 (0%) 2/39 (5.1%)
Malaise 0/16 (0%) 2/39 (5.1%)
Mucosal inflammation 2/16 (12.5%) 11/39 (28.2%)
Oedema 0/16 (0%) 2/39 (5.1%)
Oedema peripheral 2/16 (12.5%) 6/39 (15.4%)
Pain 1/16 (6.3%) 4/39 (10.3%)
Peripheral swelling 0/16 (0%) 2/39 (5.1%)
Pyrexia 1/16 (6.3%) 5/39 (12.8%)
Immune system disorders
Multiple allergies 1/16 (6.3%) 0/39 (0%)
Infections and infestations
Cellulitis 1/16 (6.3%) 0/39 (0%)
Lower respiratory tract infection 2/16 (12.5%) 1/39 (2.6%)
Nasopharyngitis 4/16 (25%) 5/39 (12.8%)
Rhinitis 0/16 (0%) 3/39 (7.7%)
Sinusitis 1/16 (6.3%) 2/39 (5.1%)
Tooth infection 2/16 (12.5%) 1/39 (2.6%)
Upper respiratory tract infection 2/16 (12.5%) 7/39 (17.9%)
Urinary tract infection 2/16 (12.5%) 5/39 (12.8%)
Viral infection 1/16 (6.3%) 0/39 (0%)
Viral upper respiratory tract infection 2/16 (12.5%) 0/39 (0%)
Eye infection 1/16 (6.3%) 0/39 (0%)
Gingivitis 1/16 (6.3%) 0/39 (0%)
Hordeolum 1/16 (6.3%) 1/39 (2.6%)
Injury, poisoning and procedural complications
Contusion 1/16 (6.3%) 3/39 (7.7%)
Epicondylitis 1/16 (6.3%) 0/39 (0%)
Fall 1/16 (6.3%) 2/39 (5.1%)
Infusion related reaction 1/16 (6.3%) 8/39 (20.5%)
Procedural pain 1/16 (6.3%) 0/39 (0%)
Eye contusion 1/16 (6.3%) 0/39 (0%)
Incisional hernia 1/16 (6.3%) 0/39 (0%)
Investigations
Alanine aminotransferase increased 6/16 (37.5%) 12/39 (30.8%)
Amylase increased 9/16 (56.3%) 10/39 (25.6%)
Aspartate aminotransferase increased 4/16 (25%) 14/39 (35.9%)
Blood alkaline phosphatase increased 1/16 (6.3%) 6/39 (15.4%)
Blood bilirubin increased 1/16 (6.3%) 2/39 (5.1%)
Blood cholesterol increased 2/16 (12.5%) 3/39 (7.7%)
Blood corticotrophin decreased 1/16 (6.3%) 0/39 (0%)
Blood creatine phosphokinase increased 3/16 (18.8%) 3/39 (7.7%)
Blood creatinine increased 5/16 (31.3%) 4/39 (10.3%)
Blood lactate dehydrogenase increased 1/16 (6.3%) 1/39 (2.6%)
Blood magnesium decreased 2/16 (12.5%) 0/39 (0%)
Blood phosphorus decreased 3/16 (18.8%) 0/39 (0%)
Blood sodium decreased 2/16 (12.5%) 0/39 (0%)
Blood thyroid stimulating hormone decreased 1/16 (6.3%) 1/39 (2.6%)
Blood thyroid stimulating hormone increased 2/16 (12.5%) 1/39 (2.6%)
Blood triglycerides increased 0/16 (0%) 3/39 (7.7%)
Blood uric acid increased 1/16 (6.3%) 1/39 (2.6%)
C-reactive protein increased 1/16 (6.3%) 0/39 (0%)
Cardiac murmur 1/16 (6.3%) 0/39 (0%)
Ejection fraction decreased 1/16 (6.3%) 2/39 (5.1%)
Gamma-glutamyltransferase increased 3/16 (18.8%) 4/39 (10.3%)
Haemoglobin increased 1/16 (6.3%) 0/39 (0%)
Lipase increased 6/16 (37.5%) 7/39 (17.9%)
Lymphocyte count decreased 2/16 (12.5%) 2/39 (5.1%)
Platelet count decreased 2/16 (12.5%) 4/39 (10.3%)
Weight decreased 2/16 (12.5%) 9/39 (23.1%)
Weight increased 1/16 (6.3%) 3/39 (7.7%)
Activated partial thromboplastin time prolonged 1/16 (6.3%) 0/39 (0%)
Blood corticotrophin increased 0/16 (0%) 2/39 (5.1%)
White blood cell count decreased 1/16 (6.3%) 1/39 (2.6%)
Metabolism and nutrition disorders
Decreased appetite 3/16 (18.8%) 10/39 (25.6%)
Dehydration 1/16 (6.3%) 3/39 (7.7%)
Gout 2/16 (12.5%) 1/39 (2.6%)
Hypercalcaemia 1/16 (6.3%) 2/39 (5.1%)
Hyperglycaemia 2/16 (12.5%) 1/39 (2.6%)
Hyperkalaemia 2/16 (12.5%) 4/39 (10.3%)
Hypernatraemia 1/16 (6.3%) 2/39 (5.1%)
Hypertriglyceridaemia 3/16 (18.8%) 4/39 (10.3%)
Hyperuricaemia 1/16 (6.3%) 6/39 (15.4%)
Hypoalbuminaemia 2/16 (12.5%) 3/39 (7.7%)
Hypokalaemia 0/16 (0%) 5/39 (12.8%)
Hypomagnesaemia 0/16 (0%) 3/39 (7.7%)
Hyponatraemia 5/16 (31.3%) 5/39 (12.8%)
Hypophosphataemia 1/16 (6.3%) 8/39 (20.5%)
Hyperlipidaemia 0/16 (0%) 2/39 (5.1%)
Musculoskeletal and connective tissue disorders
Arthralgia 7/16 (43.8%) 12/39 (30.8%)
Back pain 4/16 (25%) 5/39 (12.8%)
Flank pain 2/16 (12.5%) 1/39 (2.6%)
Joint swelling 3/16 (18.8%) 0/39 (0%)
Muscle spasms 3/16 (18.8%) 7/39 (17.9%)
Muscular weakness 1/16 (6.3%) 2/39 (5.1%)
Musculoskeletal pain 1/16 (6.3%) 2/39 (5.1%)
Musculoskeletal stiffness 1/16 (6.3%) 2/39 (5.1%)
Myalgia 3/16 (18.8%) 8/39 (20.5%)
Neck pain 0/16 (0%) 2/39 (5.1%)
Pain in extremity 3/16 (18.8%) 4/39 (10.3%)
Gouty arthritis 1/16 (6.3%) 0/39 (0%)
Musculoskeletal chest pain 1/16 (6.3%) 0/39 (0%)
Nervous system disorders
Ataxia 1/16 (6.3%) 0/39 (0%)
Dizziness 5/16 (31.3%) 4/39 (10.3%)
Dysgeusia 1/16 (6.3%) 6/39 (15.4%)
Headache 7/16 (43.8%) 8/39 (20.5%)
Hyperaesthesia 2/16 (12.5%) 0/39 (0%)
Hypoaesthesia 2/16 (12.5%) 1/39 (2.6%)
Lethargy 3/16 (18.8%) 1/39 (2.6%)
Paraesthesia 2/16 (12.5%) 3/39 (7.7%)
Tremor 2/16 (12.5%) 1/39 (2.6%)
Cognitive disorder 0/16 (0%) 3/39 (7.7%)
Neurotoxicity 1/16 (6.3%) 0/39 (0%)
Taste disorder 1/16 (6.3%) 0/39 (0%)
Psychiatric disorders
Confusional state 1/16 (6.3%) 2/39 (5.1%)
Dysphoria 1/16 (6.3%) 0/39 (0%)
Insomnia 2/16 (12.5%) 6/39 (15.4%)
Mood altered 1/16 (6.3%) 0/39 (0%)
Renal and urinary disorders
Dysuria 1/16 (6.3%) 0/39 (0%)
Proteinuria 3/16 (18.8%) 6/39 (15.4%)
Urinary incontinence 0/16 (0%) 2/39 (5.1%)
Haematuria 1/16 (6.3%) 1/39 (2.6%)
Reproductive system and breast disorders
Balanoposthitis 2/16 (12.5%) 0/39 (0%)
Breast mass 1/16 (6.3%) 0/39 (0%)
Erectile dysfunction 1/16 (6.3%) 0/39 (0%)
Testicular swelling 1/16 (6.3%) 0/39 (0%)
Respiratory, thoracic and mediastinal disorders
Cough 7/16 (43.8%) 10/39 (25.6%)
Dysphonia 7/16 (43.8%) 20/39 (51.3%)
Dyspnoea 6/16 (37.5%) 12/39 (30.8%)
Epistaxis 0/16 (0%) 2/39 (5.1%)
Hypoxia 1/16 (6.3%) 1/39 (2.6%)
Nasal congestion 1/16 (6.3%) 4/39 (10.3%)
Oropharyngeal pain 2/16 (12.5%) 5/39 (12.8%)
Productive cough 1/16 (6.3%) 3/39 (7.7%)
Pulmonary embolism 0/16 (0%) 3/39 (7.7%)
Rhinitis allergic 1/16 (6.3%) 1/39 (2.6%)
Sinus congestion 0/16 (0%) 2/39 (5.1%)
Upper-airway cough syndrome 1/16 (6.3%) 1/39 (2.6%)
Wheezing 3/16 (18.8%) 0/39 (0%)
Dyspnoea exertional 1/16 (6.3%) 0/39 (0%)
Skin and subcutaneous tissue disorders
Dermatitis acneiform 0/16 (0%) 2/39 (5.1%)
Dry skin 2/16 (12.5%) 4/39 (10.3%)
Eczema 1/16 (6.3%) 0/39 (0%)
Hyperkeratosis 1/16 (6.3%) 0/39 (0%)
Ingrowing nail 1/16 (6.3%) 0/39 (0%)
Night sweats 1/16 (6.3%) 1/39 (2.6%)
Pain of skin 0/16 (0%) 2/39 (5.1%)
Palmar-plantar erythrodysaesthesia syndrome 7/16 (43.8%) 12/39 (30.8%)
Pruritus 4/16 (25%) 10/39 (25.6%)
Rash 6/16 (37.5%) 15/39 (38.5%)
Rash erythematous 1/16 (6.3%) 0/39 (0%)
Rash macular 1/16 (6.3%) 1/39 (2.6%)
Rash papular 2/16 (12.5%) 1/39 (2.6%)
Rash pruritic 1/16 (6.3%) 0/39 (0%)
Skin exfoliation 1/16 (6.3%) 0/39 (0%)
Skin hyperpigmentation 1/16 (6.3%) 0/39 (0%)
Skin lesion 1/16 (6.3%) 0/39 (0%)
Skin ulcer 0/16 (0%) 6/39 (15.4%)
Urticaria 0/16 (0%) 2/39 (5.1%)
Actinic keratosis 1/16 (6.3%) 0/39 (0%)
Hyperhidrosis 0/16 (0%) 2/39 (5.1%)
Rash maculo-papular 0/16 (0%) 3/39 (7.7%)
Scar pain 1/16 (6.3%) 0/39 (0%)
Vascular disorders
Haematoma 1/16 (6.3%) 0/39 (0%)
Hypertension 8/16 (50%) 19/39 (48.7%)
Hypotension 1/16 (6.3%) 5/39 (12.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

Results Point of Contact

Name/Title Pfizer ClinicalTrials.gov Call Center
Organization Pfizer Inc.
Phone 1-800-718-1021
Email ClinicalTrials.gov_Inquiries@pfizer.com
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT02493751
Other Study ID Numbers:
  • B9991002
  • 2015-001137-25
  • Javelin Renal 100
First Posted:
Jul 9, 2015
Last Update Posted:
Feb 18, 2022
Last Verified:
Dec 1, 2021