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Avelumab

Axitinib

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Avelumab (MSB0010718C) in combination with axitinib (AG-013736)

Patients will receive avelumab 10 mg/kg Q2W in combination with axitinib 5 mg BID.

Avelumab (MSB0010718C)

Axitinib (AG-013736)

Pfizer CT.gov Call Center

To evaluate the safety, efficacy and PK of avelumab in combination with axitinib as first line treatment in patients with advanced HCC

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

AN OPEN LABEL, SINGLE ARM PHASE 1B STUDY OF AVELUMAB PLUS AXITINIB AS FIRST LINE TREATMENT IN PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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+ cells are the type of T-lymphocytes.

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.

Pfizer

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.

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.

Avelumab + Axitinib

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Full analysis set included participants who received at least one dose of study drug.

Pfizer ClinicalTrials.gov Call Center

Safety analysis set included participants who received at least one dose of study drug.

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

Anemia: Grade 1

Anemia: Grade 2

Hemoglobin increased: Grade 1

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

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.

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

Alanine aminotransferase (ALT) increased: Grade 1

ALT increased: Grade 2

ALT increased: Grade 3

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

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

Full analysis set included all participants who received at least one dose of study drug.

Time to Disease Progression (TTP)

Progression Free Survival (PFS)

Percentage of Participants With Objective Response (OR)

Percentage of Participants With Disease Control (DC)

Time to Tumor Response (TTR)

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.

Duration of Response (DR)

Overall Survival (OS)

Cycle 2 Day 1

Cycle 3 Day 1

Cycle 4 Day 1

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.

Maximum Observed 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 axitinib. Here, "number analyzed" signifies participants evaluable for specific time points.

Maximum Observed Plasma Concentration of Axitinib

Cycle 6 Day 1

Cycle 8 Day 1

Cycle 12 Day 1

Cycle 16 Day 1

Cycle 20 Day 1

Cycle 24 Day 1

Cycle 28 Day 1

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.

Pre-dose Serum Concentration of Avelumab

Pre-dose Plasma Concentration of Axitinib

PD-L1: Positive

PD-L1: Negative

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.

Number of Participants With Their Target Programmed Death-Ligand 1 (PD-L1) Status

CD8+ Cells in Invasive Margin

CD8+ Cells in Center of Tumor Cells

CD8+ Cells in Total Area of Tumor Cells

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.

Mean Percentage of CD8+ Cells in Per Unit Area of Invasive Margin, Center of Tumor Cells and Total Area of Tumor Cells

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.

Summary of Cluster of Differentiation 8 (CD8+) Cells Expression: Total Area Covered by CD8+ Cells in Center of Tumor Cells

ADA positive

nAb positive

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.

Number of Participants With Positive Anti-Drug Antibodies (ADAs) and Positive Neutralizing Antibodies (nAbs)

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.

Spots Global Cancer Trial Database for A Study Of Avelumab In Combination With Axitinib In Advanced HCC (VEGF Liver 100)

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