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To evaluate the safety, efficacy and PK of avelumab in combination with axitinib as first line treatment in patients with advanced HCC
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental 1 | Experimental | Avelumab (MSB0010718C) in combination with axitinib (AG-013736) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Avelumab (MSB0010718C) | Drug | Patients will receive avelumab 10 mg/kg Q2W in combination with axitinib 5 mg BID. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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= \ | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Aichi Cancer Center Hospital | Nagoya | Aichi-ken | 464-8681 | Japan | ||
| Iizuka Hospital |
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| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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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.
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Participants with advanced hepatocellular carcinoma (HCC) who did not receive any prior systemic therapy were enrolled in this study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Avelumab + Axitinib | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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Full analysis set included participants who received at least one dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Avelumab + Axitinib | 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. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Safety analysis set included participants who received at least one dose of study drug. | Posted | Count of Participants | Participants | 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) |
|
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)
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Avelumab + Axitinib | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute myocardial infarction | Cardiac disorders | MedDRA v22.1 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Adrenal insufficiency | Endocrine disorders | MedDRA v22.1 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 18, 2017 | Aug 13, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 20, 2019 | Aug 13, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D006528 | Carcinoma, Hepatocellular |
| D009369 | Neoplasms |
| D008107 | Liver Diseases |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| C000609138 | avelumab |
| D000077784 | Axitinib |
| ID | Term |
|---|---|
| D001549 | Benzamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D001565 | Benzoates |
| D000146 |
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| Axitinib (AG-013736) | Drug | Patients will receive avelumab 10 mg/kg Q2W in combination with axitinib 5 mg BID. |
|
| 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) |
| 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. | 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. | 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. | 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. | 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. | 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. | 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 | 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 | 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 | 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 | 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. | 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). | 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. | 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. | From first dose of study drug until 30 days after the last dose of study drug (maximum up to 21 months) |
| Iizuka |
| Fukuoka |
| 820-8505 |
| Japan |
| Kindai University Hospital, Department of Gastroenterology and Hepatology | Ōsaka-sayama | Osaka | 589-8511 | Japan |
| National Cancer Center Hospital | Chuo-ku | Tokyo | 104-0045 | Japan |
| Kyorin University Hospital, Department of Medical Oncology | Mitaka-shi | Tokyo | 181-8611 | Japan |
| Japanese Red Cross Musashino Hospital | Musashino | Tokyo | 180-8610 | Japan |
| National Hospital Organization Kyushu Medical Center | Fukuoka | 810-8563 | Japan |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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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.
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| Primary | 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= \ | 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. | Posted | Count of Participants | Participants | 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) |
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| Primary | 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. | 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. | Posted | Count of Participants | Participants | 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) |
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| Secondary | 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. | Full analysis set included all participants who received at least one dose of study drug. | Posted | Median | 95% Confidence Interval | Months | From first dose of study drug until first documentation of progressive disease or data censoring date, whichever occurred first (maximum up to 20 months) |
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| Secondary | 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. | Full analysis set included all participants who received at least one dose of study drug. | Posted | Median | 95% Confidence Interval | Months | 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) |
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| Secondary | 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. | Full analysis set included all participants who received at least one dose of study drug. | Posted | Number | 95% Confidence Interval | Percentage of participants | From first dose of study drug until disease progression or death due to any cause (maximum up to 20 months) |
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| Secondary | 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. | Full analysis set included all participants who received at least one dose of study drug. | Posted | Number | 95% Confidence Interval | Percentage of participants | 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) |
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| Secondary | 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. | Full analysis set included all participants who received at least one dose of study drug. | Posted | Median | Full Range | Months | From first dose of study drug until first documentation of CR or PR (maximum up to 20 months) |
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| Secondary | 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. | 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. | Posted | Median | 95% Confidence Interval | Months | 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) |
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| Secondary | 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. | Full analysis set included all participants who received at least one dose of study drug. | Posted | Median | 95% Confidence Interval | Months | 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) |
|
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|
| Secondary | Maximum Observed Serum Concentration of Avelumab | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Microgram per milliliter | Pre-dose, at the end of avelumab infusion on Day 1 of Cycle 2, 3, 4 (Duration of each cycle=14 days) |
|
|
|
| Secondary | Maximum Observed Plasma Concentration of Axitinib | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanograms per milliliter | Pre-dose, 2 hours post dose Axitinib administration on Day 1 of Cycle 2, 3 (Duration of each cycle=14 days) |
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| Secondary | Pre-dose Serum Concentration of Avelumab | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Microgram per milliliter | Pre-dose on Day 1 of Cycle 2, 3, 4, 6, 8, 12, 16, 20, 24, 28 (Duration of each cycle=14 days) |
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| Secondary | Pre-dose Plasma Concentration of Axitinib | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanograms per milliliter | Pre-dose on Day 1 of Cycle 2 and 3 (Duration of each cycle=14 days) |
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| Secondary | 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. | 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. | Posted | Count of Participants | Participants | Baseline (Day 1) |
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| Secondary | 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). | 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. | Posted | Mean | Standard Deviation | Percentage of CD8+cells per mm^2 | From first dose of study drug up to end of treatment (maximum up to 20 months) |
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| Secondary | 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. | 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. | Posted | Mean | Standard Deviation | mm^2 | From first dose of study drug up to end of treatment (up to 20 months) |
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| Secondary | 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. | 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. | Posted | Count of Participants | Participants | 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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|
|
| 12 |
| 22 |
| 8 |
| 22 |
| 22 |
| 22 |
| Diarrhoea | Gastrointestinal disorders | MedDRA v22.1 | Non-systematic Assessment |
|
| Diverticulum intestinal haemorrhagic | Gastrointestinal disorders | MedDRA v22.1 | Non-systematic Assessment |
|
| Gastric ulcer | Gastrointestinal disorders | MedDRA v22.1 | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA v22.1 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA v22.1 | Non-systematic Assessment |
|
| Malaise | General disorders | MedDRA v22.1 | Non-systematic Assessment |
|
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA v22.1 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA v22.1 | Non-systematic Assessment |
|
| Hyperthyroidism | Endocrine disorders | MedDRA v22.1 | Non-systematic Assessment |
|
| Hypothyroidism | Endocrine disorders | MedDRA v22.1 | Non-systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA v22.1 | Non-systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA v22.1 | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA v22.1 | Non-systematic Assessment |
|
| Anal erosion | Gastrointestinal disorders | MedDRA v22.1 | Non-systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA v22.1 | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA v22.1 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA v22.1 | Non-systematic Assessment |
|
| Glossitis | Gastrointestinal disorders | MedDRA v22.1 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA v22.1 | Non-systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA v22.1 | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA v22.1 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA v22.1 | Non-systematic Assessment |
|
| Malaise | General disorders | MedDRA v22.1 | Non-systematic Assessment |
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| Oedema | General disorders | MedDRA v22.1 | Non-systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA v22.1 | Non-systematic Assessment |
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| Pyrexia | General disorders | MedDRA v22.1 | Non-systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA v22.1 | Non-systematic Assessment |
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| Paronychia | Infections and infestations | MedDRA v22.1 | Non-systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA v22.1 | Non-systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA v22.1 | Non-systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA v22.1 | Non-systematic Assessment |
|
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA v22.1 | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA v22.1 | Non-systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA v22.1 | Non-systematic Assessment |
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| Blood bilirubin increased | Investigations | MedDRA v22.1 | Non-systematic Assessment |
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| Platelet count decreased | Investigations | MedDRA v22.1 | Non-systematic Assessment |
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| Transaminases increased | Investigations | MedDRA v22.1 | Non-systematic Assessment |
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| Weight decreased | Investigations | MedDRA v22.1 | Non-systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA v22.1 | Non-systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA v22.1 | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA v22.1 | Non-systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA v22.1 | Non-systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA v22.1 | Non-systematic Assessment |
|
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA v22.1 | Non-systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA v22.1 | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA v22.1 | Non-systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA v22.1 | Non-systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA v22.1 | Non-systematic Assessment |
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| Proteinuria | Renal and urinary disorders | MedDRA v22.1 | Non-systematic Assessment |
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| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA v22.1 | Non-systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA v22.1 | Non-systematic Assessment |
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| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA v22.1 | Non-systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA v22.1 | Non-systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA v22.1 | Non-systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA v22.1 | Non-systematic Assessment |
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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.
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D007191 | Indazoles |
| D011720 | Pyrazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| Title | Measurements |
|---|---|
|
| Lymphocyte count decreased: Grade 1 |
|
| Lymphocyte count decreased: Grade 2 |
|
| Lymphocyte count decreased: Grade 3 |
|
| Lymphocyte count increased: Grade 2 |
|
| Neutrophil count decreased: Grade 1 |
|
| Neutrophil count decreased: Grade 2 |
|
| Platelet count decreased: Grade 1 |
|
| Platelet count decreased: Grade 2 |
|
| White blood cell decreased: Grade 1 |
|
| White blood cell decreased: Grade 2 |
|
| Title | Measurements |
|---|---|
|
| Alkaline phosphatase (ALP) increased: Grade 1 |
|
| ALP increased: Grade 2 |
|
| ALP increased: Grade 3 |
|
| Aspartate aminotransferase(AST) increased: Grade 1 |
|
| AST increased: Grade 2 |
|
| AST increased: Grade 3 |
|
| Blood bilirubin increased: Grade 1 |
|
| Blood bilirubin increased: Grade 2 |
|
| Blood bilirubin increased: Grade 3 |
|
| Cholesterol high: Grade 1 |
|
| Cholesterol high: Grade 2 |
|
| Cholesterol high: Grade 4 |
|
| Creatine phosphokinase increased: Grade 1 |
|
| Creatine phosphokinase increased: Grade 2 |
|
| Creatinine increased: Grade 1 |
|
| Gamma-glutamyl transferase(Ggt) increased: Grade 1 |
|
| Ggt increased: Grade 2 |
|
| Ggt increased: Grade 3 |
|
| Hypercalcemia: Grade 1 |
|
| Hyperglycemia: Grade 1 |
|
| Hyperglycemia: Grade 2 |
|
| Hyperglycemia: Grade 3 |
|
| Hyperkalemia: Grade 1 |
|
| Hypermagnesemia: Grade 1 |
|
| Hypernatremia: Grade 1 |
|
| Hypertriglyceridemia; Grade 1 |
|
| Hypertriglyceridemia; Grade 2 |
|
| Hypoalbuminemia: Grade 1 |
|
| Hypoalbuminemia: Grade 2 |
|
| Hypocalcemia: Grade 1 |
|
| Hypoglycemia: Grade 1 |
|
| Hypoglycemia: Grade 2 |
|
| Hypokalemia: Grade 2 |
|
| Hypokalemia: Grade 4 |
|
| Hypomagnesemia: Grade 1 |
|
| Hyponatremia: Grade 1 |
|
| Hyponatremia: Grade 3 |
|
| Hypophosphatemia: Grade 1 |
|
| Hypophosphatemia: Grade 2 |
|
| Lipase increased: Grade 1 |
|
| Lipase increased: Grade 3 |
|
| Serum amylase increased: Grade 1 |
|
| Serum amylase increased: Grade 2 |
|
| Serum amylase increased: Grade 3 |
|
|
| Cycle 4 Day 1 |
|
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| Cycle 4 Day 1 |
|
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| Cycle 6 Day 1 |
|
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| Cycle 8 Day 1 |
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| Cycle 12 Day 1 |
|
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| Cycle 16 Day 1 |
|
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| Cycle 20 Day 1 |
|
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| Cycle 24 Day 1 |
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| Cycle 28 Day 1 |
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| CD8+ Cells in Total Area of Tumor Cells |
|
|