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A Study Of Avelumab In Combination With Axitinib In Advanced HCC (VEGF Liver 100)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03289533
Recruitment Status : Completed
First Posted : September 21, 2017
Results First Posted : September 4, 2020
Last Update Posted : September 4, 2020
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Carcinoma, Hepatocellular
Interventions Drug: Avelumab (MSB0010718C)
Drug: Axitinib (AG-013736)
Enrollment 22
Recruitment Details Participants with advanced hepatocellular carcinoma (HCC) who did not receive any prior systemic therapy were enrolled in this study.
Pre-assignment Details  
Arm/Group Title Avelumab + Axitinib
Hide Arm/Group Description Participants with advanced HCC were administered with Avelumab 10 milligram per kilogram (mg/kg) as 1-hour intravenous (IV) infusion, on Day 1 of each cycle along with Axitinib 5 milligram (mg) oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.
Period Title: Overall Study
Started 22
Completed 0
Not Completed 22
Reason Not Completed
Death             12
Terminated from study by sponsor             10
Arm/Group Title Avelumab + Axitinib
Hide Arm/Group Description Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.
Overall Number of Baseline Participants 22
Hide Baseline Analysis Population Description
Full analysis set included participants who received at least one dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 22 participants
65.4  (14.98)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants
Female
2
   9.1%
Male
20
  90.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
22
 100.0%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants
American Indian or Alaska Native
0
   0.0%
Asian
22
 100.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
0
   0.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
1.Primary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity as Graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version (v.) 4.03
Hide Description An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs were graded by investigator according to NCI CTCAE v.4.03 as follows: Grade 1: mild AE, Grade 2: moderate AE, Grade 3: severe AE, Grade 4: life-threatening consequences and urgent intervention indicated, Grade 5: death related to AE.
Time Frame From first dose of study drug up to 30 days after last dose of study drug or initiation of new anti-cancer drug therapy, whichever occurred first (maximum up to 21 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included participants who received at least one dose of study drug.
Arm/Group Title Avelumab + Axitinib
Hide Arm/Group Description:
Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.
Overall Number of Participants Analyzed 22
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 1
2
   9.1%
Grade 2
3
  13.6%
Grade 3
16
  72.7%
Grade 4
1
   4.5%
Grade 5
0
   0.0%
2.Primary Outcome
Title Number of Participants With Abnormal Laboratory Parameter Values (Hematology) as Graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) Version 4.03
Hide Description As per NCI-CTCAE v 4.03, anemia Grade 1= Less than (<) lower limit of normal (LLN) to 100 gram per liter (g/L),Grade 2= <100 to 80 g/L; hemoglobin increased: Grade 1= increase of greater than (>) 0 to 2 gram per deciliter(g/dL) above upper limit of normal [ULN]; lymphocyte count decreased: Grade 1= <LLN to 0.8*10^9/L, Grade 2= <0.8*10^9/L to 0.5*10^9/L, Grade 3= <0.5*10^9/L to 0.2*10^9/L ; lymphocyte count increased: Grade 2= >4*10^9/L to 20*10^9/L; neutrophil count decreased: Grade 1= <LLN to 1.5*10^9/L ,Grade 2= <1.5*10^9/L to 1.0*10^9/L; platelet count decreased: Grade 1= <LLN to 75.0*10^9/L, Grade 2= <75.0*10^9/L to 50.0*10^9/L; white blood cell decreased: Grade 1= <LLN to 3*10^9/L, Grade 2= <3*10^9/L to 2*10^9/L.
Time Frame From first dose of study drug up to 30 days after last dose of study drug or initiation of new anti-cancer drug therapy, whichever occurred first (maximum up to 21 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included participants who received at least one dose of study drug. Categories with at least 1 participant with abnormality were reported in this outcome measure. One participant might have more than 1 abnormality.
Arm/Group Title Avelumab + Axitinib
Hide Arm/Group Description:
Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.
Overall Number of Participants Analyzed 22
Measure Type: Count of Participants
Unit of Measure: Participants
Anemia: Grade 1
13
  59.1%
Anemia: Grade 2
3
  13.6%
Hemoglobin increased: Grade 1
5
  22.7%
Lymphocyte count decreased: Grade 1
11
  50.0%
Lymphocyte count decreased: Grade 2
2
   9.1%
Lymphocyte count decreased: Grade 3
1
   4.5%
Lymphocyte count increased: Grade 2
1
   4.5%
Neutrophil count decreased: Grade 1
3
  13.6%
Neutrophil count decreased: Grade 2
5
  22.7%
Platelet count decreased: Grade 1
14
  63.6%
Platelet count decreased: Grade 2
2
   9.1%
White blood cell decreased: Grade 1
1
   4.5%
White blood cell decreased: Grade 2
4
  18.2%
3.Primary Outcome
Title Number of Participants With Abnormal Laboratory Parameter Values (Chemistry) as Graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) Version (v) 4.03
Hide Description ALT,ALP,AST increased grades(g):g1>ULN-3.0*ULN,g2>3.0-5.0*ULN,g3>5.0-20.0*ULN; blood bilirubin increased:g1>ULN-1.5*ULN, g2>1.5-3.0*ULN, g3>3.0-10.0*ULN; [cholesterol high:g1>ULN-7.75, g2 >7.75-10.34,g4 >12.92]millimoles per liter(mmol/L);creatine phosphokinase, gamma-glutamyl transferase(ggt) increased g1>ULN-2.5*ULN, g2>2.5*ULN-5*ULN; Ggt increased g3 >5.0-20.0*ULN; Creatinine increased: g1>ULN-1.5*ULN; [hypoalbuminemia:g1<LLN-30,g2<30-20] grams per liter(g/L);[hyperglycemia:g1> ULN-8.9,g2> 8.9-13.9,g3> 13.9-27.8;hypermagnesemia:g1>ULN-1.23;hypercalcemia:g1>ULN -2.9;hyperkalemia:g1>ULN-5.5,hypernatremia:g1>ULN-150;hypertriglyceridemia g1:1.71-3.42,g2 >3.42-5.7;hypocalcemia:g1<LLN-2.0,hypoglycemia:g1<LLN-3.0, g2<3.0-2.2;hypokalemia:g2<LLN-3.0,g4<2.5,hypomagnesemia:g1<LLN-0.5,hyponatremia:g1<LLN-130, g3<130-120,hypophosphatemia:g1<LLN-0.8,g2<0.8-0.6]mmol/L;lipase increased:g1>ULN-1.5*ULN,g3 >2.0-5.0*ULN;serum amylase increased:g1>ULN-1.5*ULN, g2>1.5-2.0*ULN,g3>2.0-5.0*ULN.
Time Frame From first dose of study drug up to 30 days after last dose of study drug or initiation of new anti-cancer drug therapy, whichever occurred first (maximum up to 21 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included participants who received at least one dose of study drug. Categories with at least 1 participant with abnormality were reported in this outcome measure. One participant might have more than 1 abnormality.
Arm/Group Title Avelumab + Axitinib
Hide Arm/Group Description:
Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.
Overall Number of Participants Analyzed 22
Measure Type: Count of Participants
Unit of Measure: Participants
Alanine aminotransferase (ALT) increased: Grade 1
15
  68.2%
ALT increased: Grade 2
2
   9.1%
ALT increased: Grade 3
1
   4.5%
Alkaline phosphatase (ALP) increased: Grade 1
11
  50.0%
ALP increased: Grade 2
2
   9.1%
ALP increased: Grade 3
3
  13.6%
Aspartate aminotransferase(AST) increased: Grade 1
15
  68.2%
AST increased: Grade 2
4
  18.2%
AST increased: Grade 3
2
   9.1%
Blood bilirubin increased: Grade 1
4
  18.2%
Blood bilirubin increased: Grade 2
2
   9.1%
Blood bilirubin increased: Grade 3
1
   4.5%
Cholesterol high: Grade 1
5
  22.7%
Cholesterol high: Grade 2
1
   4.5%
Cholesterol high: Grade 4
1
   4.5%
Creatine phosphokinase increased: Grade 1
2
   9.1%
Creatine phosphokinase increased: Grade 2
1
   4.5%
Creatinine increased: Grade 1
21
  95.5%
Gamma-glutamyl transferase(Ggt) increased: Grade 1
6
  27.3%
Ggt increased: Grade 2
5
  22.7%
Ggt increased: Grade 3
7
  31.8%
Hypercalcemia: Grade 1
10
  45.5%
Hyperglycemia: Grade 1
11
  50.0%
Hyperglycemia: Grade 2
2
   9.1%
Hyperglycemia: Grade 3
1
   4.5%
Hyperkalemia: Grade 1
4
  18.2%
Hypermagnesemia: Grade 1
4
  18.2%
Hypernatremia: Grade 1
3
  13.6%
Hypertriglyceridemia; Grade 1
9
  40.9%
Hypertriglyceridemia; Grade 2
3
  13.6%
Hypoalbuminemia: Grade 1
15
  68.2%
Hypoalbuminemia: Grade 2
3
  13.6%
Hypocalcemia: Grade 1
1
   4.5%
Hypoglycemia: Grade 1
2
   9.1%
Hypoglycemia: Grade 2
1
   4.5%
Hypokalemia: Grade 2
7
  31.8%
Hypokalemia: Grade 4
1
   4.5%
Hypomagnesemia: Grade 1
2
   9.1%
Hyponatremia: Grade 1
15
  68.2%
Hyponatremia: Grade 3
1
   4.5%
Hypophosphatemia: Grade 1
4
  18.2%
Hypophosphatemia: Grade 2
8
  36.4%
Lipase increased: Grade 1
8
  36.4%
Lipase increased: Grade 3
3
  13.6%
Serum amylase increased: Grade 1
5
  22.7%
Serum amylase increased: Grade 2
1
   4.5%
Serum amylase increased: Grade 3
1
   4.5%
4.Secondary Outcome
Title Time to Disease Progression (TTP)
Hide Description TTP as assessed by investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, was define as time (in months) from date of first dose of study drug to date of first documentation of progressive disease (PD) or data censoring date, whichever occurred first. PD was defined as greater than or equal to (>=) 20 percent (%) increase in sum of diameters of target lesions, taking as a reference smallest sum on study treatment (this included baseline sum if that was smallest on study treatment), with a minimum absolute increase of at least 5 millimeter (mm), or appearance of >=1 new lesions. TTP was analyzed by Kaplan-Meier method. TTP data was censored on the date the last adequate tumor assessment for participants without PD, for participants who start new anti-cancer treatment prior to PD, for participants who died without PD, or for participants with PD after >=2 missing tumor assessments.
Time Frame From first dose of study drug until first documentation of progressive disease or data censoring date, whichever occurred first (maximum up to 20 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all participants who received at least one dose of study drug.
Arm/Group Title Avelumab + Axitinib
Hide Arm/Group Description:
Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.
Overall Number of Participants Analyzed 22
Median (95% Confidence Interval)
Unit of Measure: Months
5.52
(1.91 to 7.39)
5.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description PFS as assessed by investigator per RECIST v1.1, was defined as time (in months) from date of first dose of study drug to date of first documentation of PD or death due to any cause or data censoring date, whichever occurred first. PD: >= 20% increase in sum of diameters of target lesions, taking as a reference smallest sum on study treatment (this included baseline sum if that was smallest on study treatment). The sum must also demonstrate absolute increase of >=5 mm, or appearance of >=1 new lesions. PFS was analyzed by Kaplan-Meier method. PFS data was censored on the date the last adequate tumor assessment for participants without an event (PD or death), for participants who started new anti-cancer treatment prior to PFS event, for participants with a PFS event after >=2 missing tumor assessments.
Time Frame From first dose of study drug until first documentation of PD or death due to any cause or data censoring date, whichever occurred first (maximum up to 20 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all participants who received at least one dose of study drug.
Arm/Group Title Avelumab + Axitinib
Hide Arm/Group Description:
Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.
Overall Number of Participants Analyzed 22
Median (95% Confidence Interval)
Unit of Measure: Months
5.52
(1.91 to 7.39)
6.Secondary Outcome
Title Percentage of Participants With Objective Response (OR)
Hide Description OR as assessed by investigator per RECIST v.1.1, was defined as participants with confirmed best overall response of complete response (CR) or partial response (PR), were recorded from first dose of study drug until disease progression or death due to any cause. CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 mm. PR was defined as >=30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame From first dose of study drug until disease progression or death due to any cause (maximum up to 20 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all participants who received at least one dose of study drug.
Arm/Group Title Avelumab + Axitinib
Hide Arm/Group Description:
Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.
Overall Number of Participants Analyzed 22
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
13.6
(2.9 to 34.9)
7.Secondary Outcome
Title Percentage of Participants With Disease Control (DC)
Hide Description Disease control as assessed by investigator according to RECIST v1.1, was defined as participants with CR, PR, stable disease (SD), or non-CR/non-PD. CR: disappearance of all target and non-target lesions and sustained for 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: >= 30% decrease in sum of diameters of target lesions taking as reference baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The sum must also demonstrate an absolute increase of at least 5 mm or appearance of >=1 new lesions. Non-CR/non-PD: Persistence of any non-target lesions and/or tumor marker level above the normal limit at >=8 weeks after date of first dose of study treatment.
Time Frame From first dose of study drug until first documentation of CR or PR or SD or till non-CR/non-PD (maximum up to 20 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all participants who received at least one dose of study drug.
Arm/Group Title Avelumab + Axitinib
Hide Arm/Group Description:
Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.
Overall Number of Participants Analyzed 22
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
68.2
(45.1 to 86.1)
8.Secondary Outcome
Title Time to Tumor Response (TTR)
Hide Description TTR as assessed by investigator according to RECIST v1.1 was defined as the time (in months) from the date of first dose of study drug to the first documentation of objective response (CR or PR) that was subsequently confirmed. CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: >= 30% decrease in sum of diameter of target lesions taking as reference baseline sum diameters.
Time Frame From first dose of study drug until first documentation of CR or PR (maximum up to 20 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all participants who received at least one dose of study drug.
Arm/Group Title Avelumab + Axitinib
Hide Arm/Group Description:
Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.
Overall Number of Participants Analyzed 22
Median (Full Range)
Unit of Measure: Months
1.91
(1.9 to 3.7)
9.Secondary Outcome
Title Duration of Response (DR)
Hide Description DR as assessed by investigator according to RECIST v1.1, was defined as the time from date of first documentation of objective response (CR or PR) to date of PD or death due to any cause, or data censoring date, whichever occurred first. CR: disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (target or non-target) reduced in short axis to <10 mm. PR: >= 30% decrease in sum of diameter of target lesions taking as reference baseline sum diameters. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study treatment, with absolute increase of at least 5 mm or appearance of >=1 new lesions. DR data was censored on the date of last adequate tumor assessment for participants without an event (CR, PR, PD or death), for participants who start new anti-cancer treatment prior to DR assessment, for participants with DR assessment after >=2 missing tumor assessments.
Time Frame From first documentation of CR or PR until first documentation of tumor progression or death due to any cause or data censoring date, whichever occurred first (maximum up to 20 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all participants who received at least one dose of study drug. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Arm/Group Title Avelumab + Axitinib
Hide Arm/Group Description:
Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.
Overall Number of Participants Analyzed 3
Median (95% Confidence Interval)
Unit of Measure: Months
7.29
(3.71 to 12.94)
10.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time (in months) from the date of first dose of study drug to the date of death due to any cause or data censoring date, whichever occurred first. Participants last known to be alive were censored at the date of last contact. OS was analyzed by Kaplan-Meier method.
Time Frame From first dose of study drug to date of death from any cause or data censoring date, whichever occurred first (maximum up to 21 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all participants who received at least one dose of study drug.
Arm/Group Title Avelumab + Axitinib
Hide Arm/Group Description:
Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.
Overall Number of Participants Analyzed 22
Median (95% Confidence Interval)
Unit of Measure: Months
14.05 [1] 
(7.95 to NA)
[1]
Upper limit of 95% confidence interval (CI) could not be estimated due to low number of participants with event.
11.Secondary Outcome
Title Maximum Observed Serum Concentration of Avelumab
Hide Description [Not Specified]
Time Frame Pre-dose, at the end of avelumab infusion on Day 1 of Cycle 2, 3, 4 (Duration of each cycle=14 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) analysis set included all participants who had received at least one dose of study drug and who had at least one of the PK parameters of interest for avelumab. Here, "number analyzed" signifies participants evaluable for specific time points.
Arm/Group Title Avelumab + Axitinib
Hide Arm/Group Description:
Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.
Overall Number of Participants Analyzed 22
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Microgram per milliliter
Cycle 2 Day 1 Number Analyzed 21 participants
231.06
(24%)
Cycle 3 Day 1 Number Analyzed 22 participants
228.48
(25%)
Cycle 4 Day 1 Number Analyzed 16 participants
245.66
(26%)
12.Secondary Outcome
Title Maximum Observed Plasma Concentration of Axitinib
Hide Description [Not Specified]
Time Frame Pre-dose, 2 hours post dose Axitinib administration on Day 1 of Cycle 2, 3 (Duration of each cycle=14 days)
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set included all participants who had received at least one dose of study drug and who had at least one of the PK parameters of interest for axitinib. Here, "number analyzed" signifies participants evaluable for specific time points.
Arm/Group Title Avelumab + Axitinib
Hide Arm/Group Description:
Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.
Overall Number of Participants Analyzed 18
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Nanograms per milliliter
Cycle 2 Day 1 Number Analyzed 18 participants
89.70
(23.015%)
Cycle 3 Day 1 Number Analyzed 16 participants
109.00
(17.275%)
13.Secondary Outcome
Title Pre-dose Serum Concentration of Avelumab
Hide Description [Not Specified]
Time Frame Pre-dose on Day 1 of Cycle 2, 3, 4, 6, 8, 12, 16, 20, 24, 28 (Duration of each cycle=14 days)
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set included all participants who had received at least one dose of study drug and who had at least one of the PK parameters of interest for avelumab. Here, "number analyzed" signifies participants evaluable at specific time points.
Arm/Group Title Avelumab + Axitinib
Hide Arm/Group Description:
Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.
Overall Number of Participants Analyzed 22
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Microgram per milliliter
Cycle 2 Day 1 Number Analyzed 22 participants
33.80
(17.722%)
Cycle 3 Day 1 Number Analyzed 21 participants
19.419
(64%)
Cycle 4 Day 1 Number Analyzed 17 participants
19.220
(118%)
Cycle 6 Day 1 Number Analyzed 16 participants
23.922
(68%)
Cycle 8 Day 1 Number Analyzed 13 participants
24.814
(39%)
Cycle 12 Day 1 Number Analyzed 10 participants
29.832
(37%)
Cycle 16 Day 1 Number Analyzed 9 participants
35.388
(35%)
Cycle 20 Day 1 Number Analyzed 7 participants
31.211
(36%)
Cycle 24 Day 1 Number Analyzed 5 participants
30.070
(43%)
Cycle 28 Day 1 Number Analyzed 2 participants
35.578
(19%)
14.Secondary Outcome
Title Pre-dose Plasma Concentration of Axitinib
Hide Description [Not Specified]
Time Frame Pre-dose on Day 1 of Cycle 2 and 3 (Duration of each cycle=14 days)
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PK analysis set included all participants who had received at least one dose of study drug and who had at least one of the PK parameters of interest for axitinib. Here, "number analyzed" signifies participants evaluable for specific time points.
Arm/Group Title Avelumab + Axitinib
Hide Arm/Group Description:
Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.
Overall Number of Participants Analyzed 18
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Nanograms per milliliter
Cycle 2 Day 1 Number Analyzed 18 participants
11.6439
(123%)
Cycle 3 Day 1 Number Analyzed 16 participants
9.2226
(164%)
15.Secondary Outcome
Title Number of Participants With Their Target Programmed Death-Ligand 1 (PD-L1) Status
Hide Description PD-L1 status was defined as positive when PD-L1 staining of any intensity was observed in tumor-associated immune cells covering >= 1% of the tumor area. PD-L1 status was defined as negative when PD-L1 staining of any intensity was observed in tumor-associated immune cells covering < 1% of the tumor area.
Time Frame Baseline (Day 1)
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Hide Analysis Population Description
PD-L1 biomarker analysis set included participants who had received at least one dose of study drug and who had at least one screening biomarker assessment for PD-L1.
Arm/Group Title Avelumab + Axitinib
Hide Arm/Group Description:
Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.
Overall Number of Participants Analyzed 20
Measure Type: Count of Participants
Unit of Measure: Participants
PD-L1: Positive
17
  85.0%
PD-L1: Negative
3
  15.0%
16.Secondary Outcome
Title Mean Percentage of CD8+ Cells in Per Unit Area of Invasive Margin, Center of Tumor Cells and Total Area of Tumor Cells
Hide Description CD8+ cells are the type of T-lymphocytes. Invasive margin is defined as the region on each side of the border between tumor cells. Expression of CD8+ cells in invasive margin, center of tumor cells, total area of tumor cells has been reported as mean percentage of CD8+cells per unit area. Area was measured in millimeter square (mm^2).
Time Frame From first dose of study drug up to end of treatment (maximum up to 20 months)
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CD8+ biomarker analysis set included participants who had received at least one dose of study drug and who had at least one screening biomarker assessment for CD8+ cells. Here, "number analyzed" signifies participants evaluable for specific rows.
Arm/Group Title Avelumab + Axitinib
Hide Arm/Group Description:
Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: Percentage of CD8+cells per mm^2
CD8+ Cells in Invasive Margin Number Analyzed 7 participants
2.12  (1.760)
CD8+ Cells in Center of Tumor Cells Number Analyzed 19 participants
0.91  (1.328)
CD8+ Cells in Total Area of Tumor Cells Number Analyzed 19 participants
1.02  (1.353)
17.Secondary Outcome
Title Summary of Cluster of Differentiation 8 (CD8+) Cells Expression: Total Area Covered by CD8+ Cells in Center of Tumor Cells
Hide Description CD8+ cells are the type of T-lymphocytes.
Time Frame From first dose of study drug up to end of treatment (up to 20 months)
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Hide Analysis Population Description
CD8+ biomarker analysis set included participants who had received at least one dose of study drug and who had at least one screening biomarker assessment for CD8+ cells. Here, "Overall Number of Participants Analyzed" signifies the number of participants evaluable for this measure.
Arm/Group Title Avelumab + Axitinib
Hide Arm/Group Description:
Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.
Overall Number of Participants Analyzed 19
Mean (Standard Deviation)
Unit of Measure: mm^2
53.88  (48.832)
18.Secondary Outcome
Title Number of Participants With Positive Anti-Drug Antibodies (ADAs) and Positive Neutralizing Antibodies (nAbs)
Hide Description ADA positive was defined as presence of at least one positive ADA sample. nAb positive was defined as presence of at least one positive nAb sample.
Time Frame From first dose of study drug until 30 days after the last dose of study drug (maximum up to 21 months)
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Hide Analysis Population Description
The immunogenicity analysis set included participants who have received at least one dose of study drug and who had at least one ADA or nAb sample collected for avelumab.
Arm/Group Title Avelumab + Axitinib
Hide Arm/Group Description:
Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.
Overall Number of Participants Analyzed 22
Measure Type: Count of Participants
Unit of Measure: Participants
ADA positive
3
  13.6%
nAb positive
3
  13.6%
Time Frame From first dose of study drug up to 30 days after last dose of study drug or initiation of new anti-cancer drug therapy, whichever occurred first (maximum up to 21 months)
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 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
 
Arm/Group Title Avelumab + Axitinib
Hide Arm/Group Description Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.
All-Cause Mortality
Avelumab + Axitinib
Affected / at Risk (%)
Total   12/22 (54.55%) 
Hide Serious Adverse Events
Avelumab + Axitinib
Affected / at Risk (%)
Total   8/22 (36.36%) 
Cardiac disorders   
Acute myocardial infarction * 1  1/22 (4.55%) 
Gastrointestinal disorders   
Diarrhoea * 1  1/22 (4.55%) 
Diverticulum intestinal haemorrhagic * 1  1/22 (4.55%) 
Gastric ulcer * 1  1/22 (4.55%) 
Vomiting * 1  1/22 (4.55%) 
General disorders   
Fatigue * 1  2/22 (9.09%) 
Malaise * 1  1/22 (4.55%) 
Hepatobiliary disorders   
Hepatic function abnormal * 1  1/22 (4.55%) 
Nervous system disorders   
Headache * 1  1/22 (4.55%) 
1
Term from vocabulary, MedDRA v22.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Avelumab + Axitinib
Affected / at Risk (%)
Total   22/22 (100.00%) 
Endocrine disorders   
Adrenal insufficiency * 1  2/22 (9.09%) 
Hyperthyroidism * 1  3/22 (13.64%) 
Hypothyroidism * 1  7/22 (31.82%) 
Gastrointestinal disorders   
Abdominal discomfort * 1  2/22 (9.09%) 
Abdominal distension * 1  2/22 (9.09%) 
Abdominal pain * 1  3/22 (13.64%) 
Anal erosion * 1  2/22 (9.09%) 
Ascites * 1  3/22 (13.64%) 
Constipation * 1  7/22 (31.82%) 
Diarrhoea * 1  6/22 (27.27%) 
Glossitis * 1  2/22 (9.09%) 
Nausea * 1  3/22 (13.64%) 
Stomatitis * 1  9/22 (40.91%) 
Vomiting * 1  2/22 (9.09%) 
General disorders   
Fatigue * 1  3/22 (13.64%) 
Malaise * 1  7/22 (31.82%) 
Oedema * 1  2/22 (9.09%) 
Oedema peripheral * 1  4/22 (18.18%) 
Pyrexia * 1  6/22 (27.27%) 
Infections and infestations   
Nasopharyngitis * 1  4/22 (18.18%) 
Paronychia * 1  2/22 (9.09%) 
Upper respiratory tract infection * 1  3/22 (13.64%) 
Injury, poisoning and procedural complications   
Contusion * 1  2/22 (9.09%) 
Fall * 1  3/22 (13.64%) 
Infusion related reaction * 1  2/22 (9.09%) 
Investigations   
Alanine aminotransferase increased * 1  2/22 (9.09%) 
Aspartate aminotransferase increased * 1  2/22 (9.09%) 
Blood bilirubin increased * 1  2/22 (9.09%) 
Platelet count decreased * 1  2/22 (9.09%) 
Transaminases increased * 1  2/22 (9.09%) 
Weight decreased * 1  9/22 (40.91%) 
Metabolism and nutrition disorders   
Decreased appetite * 1  12/22 (54.55%) 
Hypoalbuminaemia * 1  2/22 (9.09%) 
Musculoskeletal and connective tissue disorders   
Arthralgia * 1  2/22 (9.09%) 
Muscle spasms * 1  2/22 (9.09%) 
Musculoskeletal pain * 1  2/22 (9.09%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Cancer pain * 1  3/22 (13.64%) 
Nervous system disorders   
Dysgeusia * 1  6/22 (27.27%) 
Headache * 1  2/22 (9.09%) 
Psychiatric disorders   
Insomnia * 1  3/22 (13.64%) 
Renal and urinary disorders   
Haematuria * 1  2/22 (9.09%) 
Proteinuria * 1  6/22 (27.27%) 
Respiratory, thoracic and mediastinal disorders   
Dysphonia * 1  11/22 (50.00%) 
Epistaxis * 1  4/22 (18.18%) 
Skin and subcutaneous tissue disorders   
Palmar-plantar erythrodysaesthesia syndrome * 1  11/22 (50.00%) 
Pruritus * 1  3/22 (13.64%) 
Rash * 1  6/22 (27.27%) 
Vascular disorders   
Hypertension * 1  17/22 (77.27%) 
1
Term from vocabulary, MedDRA v22.1
*
Indicates events were collected by non-systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
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Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT03289533    
Other Study ID Numbers: B9991024
First Submitted: August 28, 2017
First Posted: September 21, 2017
Results First Submitted: August 13, 2020
Results First Posted: September 4, 2020
Last Update Posted: September 4, 2020