A Phase 1 interventional study of Avelumab (MSB0010718C) and Axitinib (AG-013736) in Carcinoma, Hepatocellular, sponsored by Pfizer. Completed at 7 sites in Japan. Open to participants aged 20 Years and older. Per ClinicalTrials.gov, last updated 2020-09-04.
Sponsored by Pfizer · Phase 1, Interventional, and Treatment
To evaluate the safety, efficacy and PK of avelumab in combination with axitinib as first line treatment in patients with advanced HCC
Exclusion Criteria:
Avelumab (MSB0010718C) in combination with axitinib (AG-013736)
Drug: Avelumab (MSB0010718C) · Drug: Axitinib (AG-013736)
Patients will receive avelumab 10 mg/kg Q2W in combination with axitinib 5 mg BID.
Patients will receive avelumab 10 mg/kg Q2W in combination with axitinib 5 mg BID.
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
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)
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
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)
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
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)
Time to Disease Progression (TTP)
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)
Progression Free Survival (PFS)
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)
Percentage of Participants With Objective Response (OR)
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)
Percentage of Participants With Disease Control (DC)
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)
Time to Tumor Response (TTR)
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)
Duration of Response (DR)
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)
Overall Survival (OS)
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)
Maximum Observed Serum Concentration of Avelumab
Time frame: Pre-dose, at the end of avelumab infusion on Day 1 of Cycle 2, 3, 4 (Duration of each cycle=14 days)
Maximum Observed Plasma Concentration of Axitinib
Time frame: Pre-dose, 2 hours post dose Axitinib administration on Day 1 of Cycle 2, 3 (Duration of each cycle=14 days)
Pre-dose Serum Concentration of Avelumab
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)
Pre-dose Plasma Concentration of Axitinib
Time frame: Pre-dose on Day 1 of Cycle 2 and 3 (Duration of each cycle=14 days)
Number of Participants With Their Target Programmed Death-Ligand 1 (PD-L1) Status
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)
Mean Percentage of CD8+ Cells in Per Unit Area of Invasive Margin, Center of Tumor Cells and Total Area of Tumor Cells
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)
Summary of Cluster of Differentiation 8 (CD8+) Cells Expression: Total Area Covered by CD8+ Cells in Center of Tumor Cells
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)
Number of Participants With Positive Anti-Drug Antibodies (ADAs) and Positive Neutralizing Antibodies (nAbs)
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)
Participants with advanced hepatocellular carcinoma (HCC) who did not receive any prior systemic therapy were enrolled in this study.
| Milestone | Avelumab + Axitinib |
|---|---|
| Started | 22 |
| Completed | 0 |
| Not completed | 22 |
| Withdrew: Death | 12 |
| Withdrew: Terminated from study by sponsor | 10 |
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.
| Participants | Avelumab + Axitinib |
|---|---|
| Grade 1 | 2 |
| Grade 2 | 3 |
| Grade 3 | 16 |
| Grade 4 | 1 |
| Grade 5 | 0 |
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.
| Participants | Avelumab + Axitinib |
|---|---|
| Anemia: Grade 1 | 13 |
| Anemia: Grade 2 | 3 |
| Hemoglobin increased: Grade 1 | 5 |
| Lymphocyte count decreased: Grade 1 | 11 |
| Lymphocyte count decreased: Grade 2 | 2 |
| Lymphocyte count decreased: Grade 3 | 1 |
| Lymphocyte count increased: Grade 2 | 1 |
| Neutrophil count decreased: Grade 1 | 3 |
| Neutrophil count decreased: Grade 2 | 5 |
| Platelet count decreased: Grade 1 | 14 |
| Platelet count decreased: Grade 2 | 2 |
| White blood cell decreased: Grade 1 | 1 |
| White blood cell decreased: Grade 2 | 4 |
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.
| Participants | Avelumab + Axitinib |
|---|---|
| Alanine aminotransferase (ALT) increased: Grade 1 | 15 |
| ALT increased: Grade 2 | 2 |
| ALT increased: Grade 3 | 1 |
| Alkaline phosphatase (ALP) increased: Grade 1 | 11 |
| ALP increased: Grade 2 | 2 |
| ALP increased: Grade 3 | 3 |
| Aspartate aminotransferase(AST) increased: Grade 1 | 15 |
| AST increased: Grade 2 | 4 |
| AST increased: Grade 3 | 2 |
| Blood bilirubin increased: Grade 1 | 4 |
| Blood bilirubin increased: Grade 2 | 2 |
| Blood bilirubin increased: Grade 3 | 1 |
| Cholesterol high: Grade 1 | 5 |
| Cholesterol high: Grade 2 | 1 |
| Cholesterol high: Grade 4 | 1 |
| Creatine phosphokinase increased: Grade 1 | 2 |
| Creatine phosphokinase increased: Grade 2 | 1 |
| Creatinine increased: Grade 1 | 21 |
| Gamma-glutamyl transferase(Ggt) increased: Grade 1 | 6 |
| Ggt increased: Grade 2 | 5 |
| Ggt increased: Grade 3 | 7 |
| Hypercalcemia: Grade 1 | 10 |
| Hyperglycemia: Grade 1 | 11 |
| Hyperglycemia: Grade 2 | 2 |
| Hyperglycemia: Grade 3 | 1 |
| Hyperkalemia: Grade 1 | 4 |
| Hypermagnesemia: Grade 1 | 4 |
| Hypernatremia: Grade 1 | 3 |
| Hypertriglyceridemia; Grade 1 | 9 |
| Hypertriglyceridemia; Grade 2 | 3 |
| Hypoalbuminemia: Grade 1 | 15 |
| Hypoalbuminemia: Grade 2 | 3 |
| Hypocalcemia: Grade 1 | 1 |
| Hypoglycemia: Grade 1 | 2 |
| Hypoglycemia: Grade 2 | 1 |
| Hypokalemia: Grade 2 | 7 |
| Hypokalemia: Grade 4 | 1 |
| Hypomagnesemia: Grade 1 | 2 |
| Hyponatremia: Grade 1 | 15 |
| Hyponatremia: Grade 3 | 1 |
| Hypophosphatemia: Grade 1 | 4 |
| Hypophosphatemia: Grade 2 | 8 |
| Lipase increased: Grade 1 | 8 |
| Lipase increased: Grade 3 | 3 |
| Serum amylase increased: Grade 1 | 5 |
| Serum amylase increased: Grade 2 | 1 |
| Serum amylase increased: Grade 3 | 1 |
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.
| Months | Avelumab + Axitinib |
|---|---|
| Time to Disease Progression (TTP) | 5.52 (1.91 to 7.39) |
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.
| Months | Avelumab + Axitinib |
|---|---|
| Progression Free Survival (PFS) | 5.52 (1.91 to 7.39) |
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.
| Percentage of participants | Avelumab + Axitinib |
|---|---|
| Percentage of Participants With Objective Response (OR) | 13.6 (2.9 to 34.9) |
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.
| Percentage of participants | Avelumab + Axitinib |
|---|---|
| Percentage of Participants With Disease Control (DC) | 68.2 (45.1 to 86.1) |
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.
| Months | Avelumab + Axitinib |
|---|---|
| Time to Tumor Response (TTR) | 1.91 (1.9 to 3.7) |
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.
| Months | Avelumab + Axitinib |
|---|---|
| Duration of Response (DR) | 7.29 (3.71 to 12.94) |
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.
| Months | Avelumab + Axitinib |
|---|---|
| Overall Survival (OS) | 14.05 (7.95 to NA) |
| Microgram per milliliter | Avelumab + Axitinib |
|---|---|
| Cycle 2 Day 1 | 231.06 ± 24 |
| Cycle 3 Day 1 | 228.48 ± 25 |
| Cycle 4 Day 1 | 245.66 ± 26 |
| Nanograms per milliliter | Avelumab + Axitinib |
|---|---|
| Cycle 2 Day 1 | 89.70 ± 23.015 |
| Cycle 3 Day 1 | 109.00 ± 17.275 |
| Microgram per milliliter | Avelumab + Axitinib |
|---|---|
| Cycle 2 Day 1 | 33.80 ± 17.722 |
| Cycle 3 Day 1 | 19.419 ± 64 |
| Cycle 4 Day 1 | 19.220 ± 118 |
| Cycle 6 Day 1 | 23.922 ± 68 |
| Cycle 8 Day 1 | 24.814 ± 39 |
| Cycle 12 Day 1 | 29.832 ± 37 |
| Cycle 16 Day 1 | 35.388 ± 35 |
| Cycle 20 Day 1 | 31.211 ± 36 |
| Cycle 24 Day 1 | 30.070 ± 43 |
| Cycle 28 Day 1 | 35.578 ± 19 |
| Nanograms per milliliter | Avelumab + Axitinib |
|---|---|
| Cycle 2 Day 1 | 11.6439 ± 123 |
| Cycle 3 Day 1 | 9.2226 ± 164 |
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.
| Participants | Avelumab + Axitinib |
|---|---|
| PD-L1: Positive | 17 |
| PD-L1: Negative | 3 |
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).
| Percentage of CD8+cells per mm^2 | Avelumab + Axitinib |
|---|---|
| CD8+ Cells in Invasive Margin | 2.12 ± 1.760 |
| CD8+ Cells in Center of Tumor Cells | 0.91 ± 1.328 |
| CD8+ Cells in Total Area of Tumor Cells | 1.02 ± 1.353 |
CD8+ cells are the type of T-lymphocytes.
| mm^2 | Avelumab + Axitinib |
|---|---|
| Summary of Cluster of Differentiation 8 (CD8+) Cells Expression: Total Area Covered by CD8+ Cells in Center of Tumor Cells | 53.88 ± 48.832 |
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.
| Participants | Avelumab + Axitinib |
|---|---|
| ADA positive | 3 |
| nAb positive | 3 |
Collected over 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). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Avelumab + Axitinib | 12/22 (54.5%) | 8/22 (36.4%) | 22/22 (100%) |
| Event | Avelumab + Axitinib |
|---|---|
| FatigueGeneral disorders | 2/22 |
| Acute myocardial infarctionCardiac disorders | 1/22 |
| DiarrhoeaGastrointestinal disorders | 1/22 |
| Diverticulum intestinal haemorrhagicGastrointestinal disorders | 1/22 |
| Gastric ulcerGastrointestinal disorders | 1/22 |
| VomitingGastrointestinal disorders | 1/22 |
| MalaiseGeneral disorders | 1/22 |
| Hepatic function abnormalHepatobiliary disorders | 1/22 |
| HeadacheNervous system disorders | 1/22 |
| Event | Avelumab + Axitinib |
|---|---|
| HypertensionVascular disorders | 17/22 |
| Decreased appetiteMetabolism and nutrition disorders | 12/22 |
| DysphoniaRespiratory, thoracic and mediastinal disorders | 11/22 |
| Palmar-plantar erythrodysaesthesia syndromeSkin and subcutaneous tissue disorders | 11/22 |
| StomatitisGastrointestinal disorders | 9/22 |
| Weight decreasedInvestigations | 9/22 |
| HypothyroidismEndocrine disorders | 7/22 |
| ConstipationGastrointestinal disorders | 7/22 |
| MalaiseGeneral disorders | 7/22 |
| DiarrhoeaGastrointestinal disorders | 6/22 |
Full analysis set included participants who received at least one dose of study drug.
| Age, Continuous(years) | Avelumab + Axitinib |
|---|---|
| Mean | 65.4 ± 14.98 |
| Sex: Female, Male(Participants) | Avelumab + Axitinib |
|---|---|
| Female | 2 |
| Male | 20 |
| Ethnicity (NIH/OMB)(Participants) | Avelumab + Axitinib |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 22 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Avelumab + Axitinib |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 22 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 0 |
| White | 0 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: No — Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
This study is completed, as verified in Aug 2020. You cannot join it, but the record below documents what was studied.
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