Avelumab In Combination Regimens That Include An Immune Agonist, Epigenetic Modulator, CD20 Antagonist and/or Conventional Chemotherapy in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (R/R DLBCL)

AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03,severity was graded as Grade 1:asymptomatic/mild symptoms,clinical/diagnostic observations only, intervention not indicated; Grade 2:moderate, minimal, local/noninvasive intervention indicated,limiting age-appropriate instrumental activities of daily life (ADL); Grade 3:severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4:life-threatening consequence, urgent intervention indicated; Grade 5:death related to AE. TEAE was defined as events which occurred during on-treatment period beginning with first dose of study treatment through minimum (30 days + last dose of study treatment or start of new anti-cancer drug therapy). In this outcome measure participant with any TEAE of Grade 3 or above are reported.

Laboratory parameters included hematological and biochemistry: Hematological parameters included: anemia, haemoglobin increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased and white blood cells decreased. Biochemistry parameters included alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, cholesterol high, creatine kinase(cpk) increased, creatinine increased, gamma glutamyl transferase(ggt) increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypertriglyceridemia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, lipase increased,serum amylase increased.Test abnormalities were graded by NCI CTCAE version 4.03 as Grade 1=mild; Grade 2=moderate; Grade 3/Grade 4=severe/life-threatening. Number of participants with abnormalities of any grade were reported.

ECG abnormalities included: 1) QT interval, QT interval corrected using Bazett's formula (QTcB) and QT interval corrected using Fridericia's formula (QTcF): increase from baseline greater than (>) 30 millisecond (ms) or 60 ms; absolute value >450 ms, >480 ms and >500 ms; 2) heart rate (HR): absolute value <=50 beats per minute (bpm) and decrease from baseline >=20 bpm; absolute value >=120 bpm and increase from baseline >=20 bpm; 3) PR interval: absolute value >=220 ms and increase from baseline >=20 ms; 4) QRS interval: absolute value >=120 ms.

Investigator assessed DOR: was defined for participants with OR as time from first documentation of OR to time of first documentation of disease progression/death due to any cause, whichever occurred first. CR: score of 1(no uptake above background),2(uptake <=mediastinum),or 3(uptake <mediastinum but <=liver) with or without a residual mass on PET 5-PS,for lymph nodes extralymphatic sites;no new lesions;no evidence of FDG-avid disease in bone marrow. PR: >=50% decrease in SPD of up to 6 of largest dominant lymph nodes,no increase in size of other nodes,liver,spleen volume,>=50% decrease in SPD of hepatic splenic nodules,absence of other organ involvement,no new sites of disease. PD: appearance of new lesion more than 1.5 cm in any axis,at least a 50% increase from nadir in SPD/longest diameter of previous lesion/node. Data was censored on date of last adequate tumor assessment in participants with no event,started new anti-cancer therapy/had 2 or more missing assessments.

TTR was defined for participants who achieved objective response as time from randomization to first documentation of objective tumor response (CR or PR) that was subsequently confirmed. CR was defined as a score of 1 (no uptake above background), 2 (uptake <= mediastinum), or 3 (uptake <mediastinum but <=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow. PR was defined as >=50% decrease in SPD of up to six of the largest dominant lymph nodes, no increase in size of other nodes, liver, or spleen volume, a >=50% decrease in SPD of hepatic and splenic nodules, absence of other organ involvement, and no new sites of disease.

Disease control rate was defined as percentage of participants with disease control. Disease Control (DC) was defined as the best overall response of CR, PR, or stable disease (SD). CR: score of 1 (no uptake above background), 2 (uptake <= mediastinum), or 3 (uptake less than <mediastinum but <=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow. PR: >=50% decrease in SPD of up to six of the largest dominant lymph nodes, no increase in size of other nodes, liver, or spleen volume, a >=50% decrease in SPD of hepatic and splenic nodules, absence of other organ involvement, and no new sites of disease. SD: <50% decrease in SDP of up to 6 dominant, measurable nodes and extranodal sites; no criteria for progressive disease met. To qualify as a best overall response of SD, at least one SD assessment must be observed >=6 weeks after start date and before disease progression.

Investigator assessed PFS was defined as time (in months) from date of randomization to the first documentation of disease progression or death (due to any cause), whichever occurred first. PFS data was censored on the date of the last adequate tumor assessment for participants who had no an event (PD or death), for participants who start a new anti-cancer therapy prior to an event or for participants with an event after 2 or more missing or inadequate post-baseline tumor assessment. Participants without an adequate baseline or post-baseline tumor assessment were censored on the date of randomization unless death occurred on or before the time of the second planned tumor assessment in which case the death was considered as an event.

Overall survival was defined as the time (in months) from the date of randomization to the date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan-Meier method.

ADA never-positive was defined as no positive ADA results at any time point. ADA ever-positive was defined as at least one positive ADA result at any time point.

ADA never-positive was defined as no positive ADA results at any time point. ADA ever-positive was defined as at least one positive ADA result at any time point.

ADA never-positive was defined as no positive ADA results at any time point. ADA ever-positive was defined as at least one positive ADA result at any time point.

nAb never-positive was defined as no positive nAb results at any time point and nAb ever-positive was defined as at least one positive nAb result at any time point.

nAb never-positive was defined as no positive nAb results at any time point and nAb ever-positive was defined as at least one positive nAb result at any time point.

nAb never-positive was defined as no positive nAb results at any time point and nAb ever-positive was defined as at least one positive nAb result at any time point.

Percentage of Tumor and Immune Cells as Assessed by Immunohistochemistry at Baseline.

Number of participants with MRD positive, negative and not evaluable status were reported in this outcome measure.