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

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.