Trial Outcomes & Findings for 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) (NCT NCT02951156)

Last Updated: 2020-12-17

Results Overview

AEs occurring in first 4 weeks of treatment,attributable to 1 of study drugs. Hematology:1)Grade 4 neutropenia,2)Grade \>=3 febrile neutropenia with single temperature of \>38.3 degrees Celsius (C)/sustained temperature of \>=38.0 degrees C for more than 1 hour with/without associated sepsis,3)Grade \>=3 neutropenic infection,4)Grade 4 thrombocytopenia/Grade 3 thrombocytopenia with clinically significant bleeding,5)Grade 4 anemia 6)Any grade \>=3 non-hematology toxicity except:transient Grade 3 flu like symptoms/fever controlled with standard medical management;transient Grade 3 fatigue,localized skin reactions/headache that resolves to Grade \<=1;Grade 3 nausea,vomiting/diarrhea resolved to Grade \<=1 in ˂72 hours after initiation of adequate medical management;Grade 3 skin toxicity resolved to Grade \<=1 in ˂7 days;tumor flare;Single laboratory values that are out of normal range,that have no clinical correlate and resolve to Grade \<=1 within 7 days with adequate medical management.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

29 participants

Primary outcome timeframe

Day 1 Cycle 1 up to 4 Weeks

Results posted on

2020-12-17

Participant Flow

This study included participants with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after completion of at least 2 and not more than 4 lines of rituximab-containing multi-agent chemotherapy (prior to this study), and/or in whom autologous stem cell transplant (ASCT) has failed, or who were not candidates for ASCT or who were not eligible for intensive chemotherapy.

This study was planned to be conducted into two phases: Phase 1b and Phase 3. Phase 3 of the study was never conducted due to early termination of study because of Phase 1b enrollment closure.

Participant milestones

Participant milestones
Measure	Avelumab+Rituximab+Utomilumab Avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Rituximab 375 milligram per meter square (mg/m\^2) IV infusion was administered on Day 1 of each treatment cycle (maximum of 8 cycles), along with fixed dose of 100 mg IV infusion of utomilumab on Day 2 of each treatment cycle in Cycles 1 and 2. If the dose of utomilumab was well tolerated, then it was administered on Day 1 of Cycle 3 and all subsequent cycles until the participant no longer received clinical benefit. The duration of each treatment cycle was 28 days.	Avelumab+Azacitidine+Utomilumab Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Azacitidine 40 mg/m\^2 subcutaneous (SC) dose was administered on Days 1 to 5 of each treatment cycle until the participant no longer received clinical benefit, along with fixed dose of 100 mg IV infusion of utomilumab on Day 2 of each treatment cycle in Cycles 1 and 2. If the dose of utomilumab was well tolerated, then it was administered on Day 1 of Cycle 3 and all subsequent cycles until the participant no longer received clinical benefit. The duration of each treatment cycle was 28 days.	Avelumab+Bendamustine+Rituximab Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Rituximab 375 mg/m\^2 IV infusion was administered on Day 1 of each treatment cycle (maximum of 8 cycles), along with 90 mg/m\^2 IV infusion of bendamustine on Day 2 and Day 3 of each treatment cycle in Cycles 1 and 2. If the dose of bendamustine was well tolerated, then it was administered on Day 1 and Day 2 in Cycle 3 and all subsequent cycles for a maximum of 6 cycles. The duration of each treatment cycle was 28 days.
Overall Study STARTED	9	9	11
Overall Study COMPLETED	0	0	1
Overall Study NOT COMPLETED	9	9	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Avelumab+Rituximab+Utomilumab Avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Rituximab 375 milligram per meter square (mg/m\^2) IV infusion was administered on Day 1 of each treatment cycle (maximum of 8 cycles), along with fixed dose of 100 mg IV infusion of utomilumab on Day 2 of each treatment cycle in Cycles 1 and 2. If the dose of utomilumab was well tolerated, then it was administered on Day 1 of Cycle 3 and all subsequent cycles until the participant no longer received clinical benefit. The duration of each treatment cycle was 28 days.	Avelumab+Azacitidine+Utomilumab Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Azacitidine 40 mg/m\^2 subcutaneous (SC) dose was administered on Days 1 to 5 of each treatment cycle until the participant no longer received clinical benefit, along with fixed dose of 100 mg IV infusion of utomilumab on Day 2 of each treatment cycle in Cycles 1 and 2. If the dose of utomilumab was well tolerated, then it was administered on Day 1 of Cycle 3 and all subsequent cycles until the participant no longer received clinical benefit. The duration of each treatment cycle was 28 days.	Avelumab+Bendamustine+Rituximab Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Rituximab 375 mg/m\^2 IV infusion was administered on Day 1 of each treatment cycle (maximum of 8 cycles), along with 90 mg/m\^2 IV infusion of bendamustine on Day 2 and Day 3 of each treatment cycle in Cycles 1 and 2. If the dose of bendamustine was well tolerated, then it was administered on Day 1 and Day 2 in Cycle 3 and all subsequent cycles for a maximum of 6 cycles. The duration of each treatment cycle was 28 days.
Overall Study Death	3	8	5
Overall Study Progressive disease	1	0	1
Overall Study Withdrawal by Subject	0	0	1
Overall Study Study terminated by sponsor	0	0	1
Overall Study Other	5	1	2

Baseline Characteristics

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)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Avelumab+Rituximab+Utomilumab n=9 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Rituximab 375 mg/m\^2 IV infusion was administered on Day 1 of each treatment cycle (maximum of 8 cycles), along with fixed dose of 100 mg IV infusion of utomilumab on Day 2 of each treatment cycle in Cycles 1 and 2. If the dose of utomilumab was well tolerated, then it was administered on Day 1 of Cycle 3 and all subsequent cycles until the participant no longer received clinical benefit. The duration of each treatment cycle was 28 days.	Avelumab+Azacitidine+Utomilumab n=9 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Azacitidine 40 mg/m\^2 SC dose was administered on Days 1 to 5 of each treatment cycle until the participant no longer received clinical benefit, along with fixed dose of 100 mg IV infusion of utomilumab on Day 2 of each treatment cycle in Cycles 1 and 2. If the dose of utomilumab was well tolerated, then it was administered on Day 1 of Cycle 3 and all subsequent cycles until the participant no longer received clinical benefit. The duration of each treatment cycle was 28 days.	Avelumab+Bendamustine+Rituximab n=11 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Rituximab 375 mg/m\^2 IV infusion was administered on Day 1 of each treatment cycle (maximum of 8 cycles), along with 90 mg/m\^2 IV infusion of bendamustine on Day 2 and Day 3 of each treatment cycle in Cycles 1 and 2. If the dose of bendamustine was well tolerated, then it was administered on Day 1 and Day 2 in Cycle 3 and all subsequent cycles for a maximum of 6 cycles. The duration of each treatment cycle was 28 days.	Total n=29 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	10 Participants n=4 Participants
Age, Categorical >=65 years	7 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	19 Participants n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants	24 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants	26 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Race: White	8 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants	27 Participants n=4 Participants
Race/Ethnicity, Customized Race: Other	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants

PRIMARY outcome

Timeframe: Day 1 Cycle 1 up to 4 Weeks

Population: DLT evaluable set included all participants who were randomized in the study and received at least 1 dose of study medication and either experienced DLT during the first cycle, or completed the primary DLT observation period of 4 weeks.

Outcome measures

Outcome measures
Measure	Avelumab+Rituximab+Utomilumab n=7 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Rituximab 375 mg/m\^2 IV infusion was administered on Day 1 of each treatment cycle (maximum of 8 cycles), along with fixed dose of 100 mg IV infusion of utomilumab on Day 2 of each treatment cycle in Cycles 1 and 2. If the dose of utomilumab was well tolerated, then it was administered on Day 1 of Cycle 3 and all subsequent cycles until the participant no longer received clinical benefit. The duration of each treatment cycle was 28 days.	Avelumab+Azacitidine+Utomilumab n=5 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Azacitidine 40 mg/m\^2 SC dose was administered on Days 1 to 5 of each treatment cycle until the participant no longer received clinical benefit, along with fixed dose of 100 mg IV infusion of utomilumab on Day 2 of each treatment cycle in Cycles 1 and 2. If the dose of utomilumab was well tolerated, then it was administered on Day 1 of Cycle 3 and all subsequent cycles until the participant no longer received clinical benefit. The duration of each treatment cycle was 28 days.	Avelumab+Bendamustine+Rituximab n=10 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Rituximab 375 mg/m\^2 IV infusion was administered on Day 1 of each treatment cycle (maximum of 8 cycles), along with 90 mg/m\^2 IV infusion of bendamustine on Day 2 and Day 3 of each treatment cycle in Cycles 1 and 2. If the dose of bendamustine was well tolerated, then it was administered on Day 1 and Day 2 in Cycle 3 and all subsequent cycles for a maximum of 6 cycles. The duration of each treatment cycle was 28 days.
Number of Participants With Dose Limiting Toxicities (DLT)	1 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Randomization until date of PD, start of new anticancer therapy, discontinuation from study or death due to any cause, whichever occurred first (maximum up to 36 months)

Population: Full analysis set population included all participants who were randomized in the study.

ORR was defined as percentage of participants with complete response (CR) or partial response (PR), as assessed by investigator per lugano response classification criteria. CR was defined as a score of 1 (no uptake above background), 2 (uptake less than or equal to \[\<=\] mediastinum), or 3 (uptake less than \[\<\] mediastinum but \<=liver) with or without a residual mass on PET 5-point scale (5-PS), for lymph nodes and extralymphatic sites; no new lesions; no evidence of fluorodeoxyglucose (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 sum of products of diameters (SPD) of hepatic and splenic nodules, absence of other organ involvement, and no new sites of disease.

Outcome measures

Outcome measures
Measure	Avelumab+Rituximab+Utomilumab n=9 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Rituximab 375 mg/m\^2 IV infusion was administered on Day 1 of each treatment cycle (maximum of 8 cycles), along with fixed dose of 100 mg IV infusion of utomilumab on Day 2 of each treatment cycle in Cycles 1 and 2. If the dose of utomilumab was well tolerated, then it was administered on Day 1 of Cycle 3 and all subsequent cycles until the participant no longer received clinical benefit. The duration of each treatment cycle was 28 days.	Avelumab+Azacitidine+Utomilumab n=9 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Azacitidine 40 mg/m\^2 SC dose was administered on Days 1 to 5 of each treatment cycle until the participant no longer received clinical benefit, along with fixed dose of 100 mg IV infusion of utomilumab on Day 2 of each treatment cycle in Cycles 1 and 2. If the dose of utomilumab was well tolerated, then it was administered on Day 1 of Cycle 3 and all subsequent cycles until the participant no longer received clinical benefit. The duration of each treatment cycle was 28 days.	Avelumab+Bendamustine+Rituximab n=11 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Rituximab 375 mg/m\^2 IV infusion was administered on Day 1 of each treatment cycle (maximum of 8 cycles), along with 90 mg/m\^2 IV infusion of bendamustine on Day 2 and Day 3 of each treatment cycle in Cycles 1 and 2. If the dose of bendamustine was well tolerated, then it was administered on Day 1 and Day 2 in Cycle 3 and all subsequent cycles for a maximum of 6 cycles. The duration of each treatment cycle was 28 days.
Objective Response Rate (ORR) as Assessed by Investigator Per Lugano Response Classification Criteria	11.1 Percentage of participants Interval 0.3 to 48.2	0 Percentage of participants Interval 0.0 to 33.6	27.3 Percentage of participants Interval 6.0 to 61.0

SECONDARY outcome

Timeframe: From first dose of study treatment up to at least 30 days after the last dose of study treatment or initiation of new anti-cancer therapy (up to 36 months)

Population: Safety analysis set population included all participants who received at least 1 dose of study drug.

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.

Outcome measures

Outcome measures
Measure	Avelumab+Rituximab+Utomilumab n=8 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Rituximab 375 mg/m\^2 IV infusion was administered on Day 1 of each treatment cycle (maximum of 8 cycles), along with fixed dose of 100 mg IV infusion of utomilumab on Day 2 of each treatment cycle in Cycles 1 and 2. If the dose of utomilumab was well tolerated, then it was administered on Day 1 of Cycle 3 and all subsequent cycles until the participant no longer received clinical benefit. The duration of each treatment cycle was 28 days.	Avelumab+Azacitidine+Utomilumab n=9 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Azacitidine 40 mg/m\^2 SC dose was administered on Days 1 to 5 of each treatment cycle until the participant no longer received clinical benefit, along with fixed dose of 100 mg IV infusion of utomilumab on Day 2 of each treatment cycle in Cycles 1 and 2. If the dose of utomilumab was well tolerated, then it was administered on Day 1 of Cycle 3 and all subsequent cycles until the participant no longer received clinical benefit. The duration of each treatment cycle was 28 days.	Avelumab+Bendamustine+Rituximab n=11 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Rituximab 375 mg/m\^2 IV infusion was administered on Day 1 of each treatment cycle (maximum of 8 cycles), along with 90 mg/m\^2 IV infusion of bendamustine on Day 2 and Day 3 of each treatment cycle in Cycles 1 and 2. If the dose of bendamustine was well tolerated, then it was administered on Day 1 and Day 2 in Cycle 3 and all subsequent cycles for a maximum of 6 cycles. The duration of each treatment cycle was 28 days.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Greater Than or Equal to (>=) Grade 3, As Per National Cancer Institute Common Terminology Criteria For Adverse Events (NCI-CTCAE), Version 4.03	4 Participants	7 Participants	10 Participants

SECONDARY outcome

Timeframe: From first dose of study treatment up to at least 30 days after the last dose of study treatment or initiation of new anti-cancer therapy (up to 36 months)

Population: Safety analysis set population included all participants who received at least 1 dose of study drug. Here, "Number Analyzed" signifies number of participants evaluable for specified rows.

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.

Outcome measures

Outcome measures
Measure	Avelumab+Rituximab+Utomilumab n=8 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Rituximab 375 mg/m\^2 IV infusion was administered on Day 1 of each treatment cycle (maximum of 8 cycles), along with fixed dose of 100 mg IV infusion of utomilumab on Day 2 of each treatment cycle in Cycles 1 and 2. If the dose of utomilumab was well tolerated, then it was administered on Day 1 of Cycle 3 and all subsequent cycles until the participant no longer received clinical benefit. The duration of each treatment cycle was 28 days.	Avelumab+Azacitidine+Utomilumab n=9 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Azacitidine 40 mg/m\^2 SC dose was administered on Days 1 to 5 of each treatment cycle until the participant no longer received clinical benefit, along with fixed dose of 100 mg IV infusion of utomilumab on Day 2 of each treatment cycle in Cycles 1 and 2. If the dose of utomilumab was well tolerated, then it was administered on Day 1 of Cycle 3 and all subsequent cycles until the participant no longer received clinical benefit. The duration of each treatment cycle was 28 days.	Avelumab+Bendamustine+Rituximab n=11 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Rituximab 375 mg/m\^2 IV infusion was administered on Day 1 of each treatment cycle (maximum of 8 cycles), along with 90 mg/m\^2 IV infusion of bendamustine on Day 2 and Day 3 of each treatment cycle in Cycles 1 and 2. If the dose of bendamustine was well tolerated, then it was administered on Day 1 and Day 2 in Cycle 3 and all subsequent cycles for a maximum of 6 cycles. The duration of each treatment cycle was 28 days.
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 GGT increased	3 Participants	4 Participants	6 Participants
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 Hypertriglyceridemia	3 Participants	3 Participants	7 Participants
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 Anemia	6 Participants	8 Participants	10 Participants
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 Hemoglobin increased	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 Lymphocyte count decreased	4 Participants	7 Participants	9 Participants
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 Lymphocyte count increased	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 Neutrophil count decreased	2 Participants	2 Participants	9 Participants
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 Platelet count decreased	4 Participants	3 Participants	8 Participants
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 White blood cell decreased	1 Participants	4 Participants	8 Participants
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 Alanine aminotransferase increased	2 Participants	5 Participants	2 Participants
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 Alkaline phosphatase increased	3 Participants	4 Participants	6 Participants
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 Aspartate aminotransferase increased	3 Participants	6 Participants	3 Participants
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 Blood bilirubin increased	0 Participants	3 Participants	3 Participants
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 Cholesterol high	2 Participants	3 Participants	3 Participants
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 Cpk increased	2 Participants	1 Participants	2 Participants
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 Creatinine increased	6 Participants	6 Participants	10 Participants
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 Hypercalcemia	0 Participants	3 Participants	2 Participants
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 Hyperglycemia	3 Participants	1 Participants	2 Participants
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 Hyperkalemia	0 Participants	0 Participants	2 Participants
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 Hypermagnesemia	1 Participants	1 Participants	1 Participants
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 Hypernatremia	0 Participants	0 Participants	1 Participants
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 Hypoalbuminemia	3 Participants	4 Participants	6 Participants
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 Hypocalcemia	1 Participants	0 Participants	2 Participants
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 Hypoglycemia	0 Participants	0 Participants	1 Participants
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 Hypokalemia	1 Participants	1 Participants	4 Participants
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 Hypomagnesemia	0 Participants	0 Participants	4 Participants
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 Hyponatremia	0 Participants	1 Participants	3 Participants
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 Hypophosphatemia	1 Participants	0 Participants	5 Participants
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 Lipase increased	1 Participants	2 Participants	3 Participants
Number of Participants With Laboratory Abnormalities As Per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 Serum amylase increased	2 Participants	1 Participants	3 Participants

SECONDARY outcome

Timeframe: From first dose of study treatment up to at least 30 days after the last dose of study treatment or initiation of new anti-cancer therapy (up to 36 months)

Population: Safety analysis set population included all participants who received at least 1 dose of study drug. Here, "Number Analyzed" signifies number of participants evaluable for specified rows.

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.

Outcome measures

Outcome measures
Measure	Avelumab+Rituximab+Utomilumab n=8 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Rituximab 375 mg/m\^2 IV infusion was administered on Day 1 of each treatment cycle (maximum of 8 cycles), along with fixed dose of 100 mg IV infusion of utomilumab on Day 2 of each treatment cycle in Cycles 1 and 2. If the dose of utomilumab was well tolerated, then it was administered on Day 1 of Cycle 3 and all subsequent cycles until the participant no longer received clinical benefit. The duration of each treatment cycle was 28 days.	Avelumab+Azacitidine+Utomilumab n=9 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Azacitidine 40 mg/m\^2 SC dose was administered on Days 1 to 5 of each treatment cycle until the participant no longer received clinical benefit, along with fixed dose of 100 mg IV infusion of utomilumab on Day 2 of each treatment cycle in Cycles 1 and 2. If the dose of utomilumab was well tolerated, then it was administered on Day 1 of Cycle 3 and all subsequent cycles until the participant no longer received clinical benefit. The duration of each treatment cycle was 28 days.	Avelumab+Bendamustine+Rituximab n=11 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Rituximab 375 mg/m\^2 IV infusion was administered on Day 1 of each treatment cycle (maximum of 8 cycles), along with 90 mg/m\^2 IV infusion of bendamustine on Day 2 and Day 3 of each treatment cycle in Cycles 1 and 2. If the dose of bendamustine was well tolerated, then it was administered on Day 1 and Day 2 in Cycle 3 and all subsequent cycles for a maximum of 6 cycles. The duration of each treatment cycle was 28 days.
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcF: >450 ms	4 Participants	3 Participants	6 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcF: >500 ms	0 Participants	2 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QT: Increase from baseline >30 ms	4 Participants	4 Participants	4 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QT: Increase from baseline >60 ms	1 Participants	3 Participants	2 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QT: >450 ms	2 Participants	2 Participants	2 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QT: >480 ms	0 Participants	1 Participants	1 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QT: >500 ms	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcB: Increase from baseline >30 ms	1 Participants	3 Participants	4 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcB: Increase from baseline >60 ms	1 Participants	1 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcB: >450 ms	4 Participants	5 Participants	9 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcB: >480 ms	2 Participants	3 Participants	4 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcB: >500 ms	1 Participants	2 Participants	1 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcF: Increase from baseline >30 ms	1 Participants	3 Participants	3 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcF: Increase from baseline >60 ms	0 Participants	2 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcF: >480 ms	0 Participants	2 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities Heart rate: <=50 bpm and decrease from baseline >=20 bpm	0 Participants	1 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities Heart rate: >=120 bpm and increase from baseline >=20 bpm	0 Participants	0 Participants	1 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities PR: >=220 ms and increase from baseline >=20 ms	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QRS: >=120 ms	1 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: First response (CR or PR) to date of PD, start of new anti-cancer therapy, discontinuation from the study, censoring date or death due to any cause, whichever occurred first (maximum up to 36 months)

Population: Participants who were randomized and achieved an objective response.

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.

Outcome measures

Outcome measures
Measure	Avelumab+Rituximab+Utomilumab n=1 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Rituximab 375 mg/m\^2 IV infusion was administered on Day 1 of each treatment cycle (maximum of 8 cycles), along with fixed dose of 100 mg IV infusion of utomilumab on Day 2 of each treatment cycle in Cycles 1 and 2. If the dose of utomilumab was well tolerated, then it was administered on Day 1 of Cycle 3 and all subsequent cycles until the participant no longer received clinical benefit. The duration of each treatment cycle was 28 days.	Avelumab+Azacitidine+Utomilumab Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Azacitidine 40 mg/m\^2 SC dose was administered on Days 1 to 5 of each treatment cycle until the participant no longer received clinical benefit, along with fixed dose of 100 mg IV infusion of utomilumab on Day 2 of each treatment cycle in Cycles 1 and 2. If the dose of utomilumab was well tolerated, then it was administered on Day 1 of Cycle 3 and all subsequent cycles until the participant no longer received clinical benefit. The duration of each treatment cycle was 28 days.	Avelumab+Bendamustine+Rituximab n=3 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Rituximab 375 mg/m\^2 IV infusion was administered on Day 1 of each treatment cycle (maximum of 8 cycles), along with 90 mg/m\^2 IV infusion of bendamustine on Day 2 and Day 3 of each treatment cycle in Cycles 1 and 2. If the dose of bendamustine was well tolerated, then it was administered on Day 1 and Day 2 in Cycle 3 and all subsequent cycles for a maximum of 6 cycles. The duration of each treatment cycle was 28 days.
Duration of Response (DOR) as Assessed by Investigator Per Lugano Response Classification Criteria	1.81 Months Interval 1.81 to 1.81	—	NA Months Median and full range could not be calculated as all 3 participants who achieved OR were not observed to have PD or death on study

SECONDARY outcome

Timeframe: From the date of randomization to the first documentation of objective response (CR or PR) (maximum up to 36 months)

Population: Participants who were randomized and achieved an objective response.

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.

Outcome measures

Outcome measures
Measure	Avelumab+Rituximab+Utomilumab n=1 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Rituximab 375 mg/m\^2 IV infusion was administered on Day 1 of each treatment cycle (maximum of 8 cycles), along with fixed dose of 100 mg IV infusion of utomilumab on Day 2 of each treatment cycle in Cycles 1 and 2. If the dose of utomilumab was well tolerated, then it was administered on Day 1 of Cycle 3 and all subsequent cycles until the participant no longer received clinical benefit. The duration of each treatment cycle was 28 days.	Avelumab+Azacitidine+Utomilumab Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Azacitidine 40 mg/m\^2 SC dose was administered on Days 1 to 5 of each treatment cycle until the participant no longer received clinical benefit, along with fixed dose of 100 mg IV infusion of utomilumab on Day 2 of each treatment cycle in Cycles 1 and 2. If the dose of utomilumab was well tolerated, then it was administered on Day 1 of Cycle 3 and all subsequent cycles until the participant no longer received clinical benefit. The duration of each treatment cycle was 28 days.	Avelumab+Bendamustine+Rituximab n=3 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Rituximab 375 mg/m\^2 IV infusion was administered on Day 1 of each treatment cycle (maximum of 8 cycles), along with 90 mg/m\^2 IV infusion of bendamustine on Day 2 and Day 3 of each treatment cycle in Cycles 1 and 2. If the dose of bendamustine was well tolerated, then it was administered on Day 1 and Day 2 in Cycle 3 and all subsequent cycles for a maximum of 6 cycles. The duration of each treatment cycle was 28 days.
Time to Tumor Response (TTR) as Assessed by Investigator Per Lugano Response Classification Criteria	1.8 Months Interval 1.8 to 1.8	—	1.9 Months Interval 1.7 to 2.6

SECONDARY outcome

Timeframe: From the date of randomization to the first documentation of PD, study discontinuation, start of new anti-cancer therapy or death due to any cause, whichever occurred first (maximum up to 36 months)

Population: Full analysis set population included all participants who were randomized in the study.

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.

Outcome measures

Outcome measures
Measure	Avelumab+Rituximab+Utomilumab n=9 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Rituximab 375 mg/m\^2 IV infusion was administered on Day 1 of each treatment cycle (maximum of 8 cycles), along with fixed dose of 100 mg IV infusion of utomilumab on Day 2 of each treatment cycle in Cycles 1 and 2. If the dose of utomilumab was well tolerated, then it was administered on Day 1 of Cycle 3 and all subsequent cycles until the participant no longer received clinical benefit. The duration of each treatment cycle was 28 days.	Avelumab+Azacitidine+Utomilumab n=9 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Azacitidine 40 mg/m\^2 SC dose was administered on Days 1 to 5 of each treatment cycle until the participant no longer received clinical benefit, along with fixed dose of 100 mg IV infusion of utomilumab on Day 2 of each treatment cycle in Cycles 1 and 2. If the dose of utomilumab was well tolerated, then it was administered on Day 1 of Cycle 3 and all subsequent cycles until the participant no longer received clinical benefit. The duration of each treatment cycle was 28 days.	Avelumab+Bendamustine+Rituximab n=11 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Rituximab 375 mg/m\^2 IV infusion was administered on Day 1 of each treatment cycle (maximum of 8 cycles), along with 90 mg/m\^2 IV infusion of bendamustine on Day 2 and Day 3 of each treatment cycle in Cycles 1 and 2. If the dose of bendamustine was well tolerated, then it was administered on Day 1 and Day 2 in Cycle 3 and all subsequent cycles for a maximum of 6 cycles. The duration of each treatment cycle was 28 days.
Disease Control Rate as Assessed by the Investigator Per Lugano Response Classification Criteria	22.2 Percentage of participants Interval 2.8 to 60.0	0 Percentage of participants Interval 0.0 to 33.6	36.4 Percentage of participants Interval 10.9 to 69.2

SECONDARY outcome

Timeframe: From the date of randomization to progression of disease, study discontinuation, censoring date or death due to any cause, whichever occurred first (up to 36 months)

Population: Full analysis set population included all participants who were randomized in the study.

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.

Outcome measures

Outcome measures
Measure	Avelumab+Rituximab+Utomilumab n=9 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Rituximab 375 mg/m\^2 IV infusion was administered on Day 1 of each treatment cycle (maximum of 8 cycles), along with fixed dose of 100 mg IV infusion of utomilumab on Day 2 of each treatment cycle in Cycles 1 and 2. If the dose of utomilumab was well tolerated, then it was administered on Day 1 of Cycle 3 and all subsequent cycles until the participant no longer received clinical benefit. The duration of each treatment cycle was 28 days.	Avelumab+Azacitidine+Utomilumab n=9 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Azacitidine 40 mg/m\^2 SC dose was administered on Days 1 to 5 of each treatment cycle until the participant no longer received clinical benefit, along with fixed dose of 100 mg IV infusion of utomilumab on Day 2 of each treatment cycle in Cycles 1 and 2. If the dose of utomilumab was well tolerated, then it was administered on Day 1 of Cycle 3 and all subsequent cycles until the participant no longer received clinical benefit. The duration of each treatment cycle was 28 days.	Avelumab+Bendamustine+Rituximab n=11 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Rituximab 375 mg/m\^2 IV infusion was administered on Day 1 of each treatment cycle (maximum of 8 cycles), along with 90 mg/m\^2 IV infusion of bendamustine on Day 2 and Day 3 of each treatment cycle in Cycles 1 and 2. If the dose of bendamustine was well tolerated, then it was administered on Day 1 and Day 2 in Cycle 3 and all subsequent cycles for a maximum of 6 cycles. The duration of each treatment cycle was 28 days.
Progression-Free Survival (PFS) as Assessed by the Investigator Per Lugano Response Classification Criteria	1.8 Months Interval 0.6 to 3.5	1.5 Months Interval 0.3 to 1.8	2.7 Months Interval 1.3 to Due to small number of participants who had events, upper limit of 95% CI was not estimable.

SECONDARY outcome

Timeframe: From the date of randomization to discontinuation from the study or death, whichever occurred first (maximum up to 36 months)

Population: Full analysis set population included all participants who were randomized in the study.

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.

Outcome measures

Outcome measures
Measure	Avelumab+Rituximab+Utomilumab n=9 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Rituximab 375 mg/m\^2 IV infusion was administered on Day 1 of each treatment cycle (maximum of 8 cycles), along with fixed dose of 100 mg IV infusion of utomilumab on Day 2 of each treatment cycle in Cycles 1 and 2. If the dose of utomilumab was well tolerated, then it was administered on Day 1 of Cycle 3 and all subsequent cycles until the participant no longer received clinical benefit. The duration of each treatment cycle was 28 days.	Avelumab+Azacitidine+Utomilumab n=9 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Azacitidine 40 mg/m\^2 SC dose was administered on Days 1 to 5 of each treatment cycle until the participant no longer received clinical benefit, along with fixed dose of 100 mg IV infusion of utomilumab on Day 2 of each treatment cycle in Cycles 1 and 2. If the dose of utomilumab was well tolerated, then it was administered on Day 1 of Cycle 3 and all subsequent cycles until the participant no longer received clinical benefit. The duration of each treatment cycle was 28 days.	Avelumab+Bendamustine+Rituximab n=11 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Rituximab 375 mg/m\^2 IV infusion was administered on Day 1 of each treatment cycle (maximum of 8 cycles), along with 90 mg/m\^2 IV infusion of bendamustine on Day 2 and Day 3 of each treatment cycle in Cycles 1 and 2. If the dose of bendamustine was well tolerated, then it was administered on Day 1 and Day 2 in Cycle 3 and all subsequent cycles for a maximum of 6 cycles. The duration of each treatment cycle was 28 days.
Overall Survival	14.8 Months Interval 0.9 to Due to small number of participants who had events, upper limit of 95% CI was not estimable.	4.0 Months Interval 0.3 to 11.3	5.2 Months Interval 1.3 to Due to small number of participants who had events, upper limit of 95% CI was not estimable.

SECONDARY outcome

Timeframe: 1 hour Post dose Day 2 Cycle 1, 144 hour Post dose Day 8 of Cycle 1, 0 hour Post dose Day 16 of Cycle 1, Day 1 of Cycle 4 and Cycle 6

Population: Avelumab pharmacokinetic concentration analysis set included all participants who received at least 1 dose of study drug and who had at least 1 post-dose concentration measurement above the lower limit of quantitation for avelumab. Here, "Number Analyzed" signifies number of participants evaluable for specified rows.

Outcome measures

Outcome measures
Measure	Avelumab+Rituximab+Utomilumab n=8 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Rituximab 375 mg/m\^2 IV infusion was administered on Day 1 of each treatment cycle (maximum of 8 cycles), along with fixed dose of 100 mg IV infusion of utomilumab on Day 2 of each treatment cycle in Cycles 1 and 2. If the dose of utomilumab was well tolerated, then it was administered on Day 1 of Cycle 3 and all subsequent cycles until the participant no longer received clinical benefit. The duration of each treatment cycle was 28 days.	Avelumab+Azacitidine+Utomilumab n=9 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Azacitidine 40 mg/m\^2 SC dose was administered on Days 1 to 5 of each treatment cycle until the participant no longer received clinical benefit, along with fixed dose of 100 mg IV infusion of utomilumab on Day 2 of each treatment cycle in Cycles 1 and 2. If the dose of utomilumab was well tolerated, then it was administered on Day 1 of Cycle 3 and all subsequent cycles until the participant no longer received clinical benefit. The duration of each treatment cycle was 28 days.	Avelumab+Bendamustine+Rituximab n=11 Participants Avelumab 10 mg/kg IV infusion was administered every 2 weeks on Day 2 and Day 16 of Cycles 1 and 2, if well tolerated then continued on Day 1 and Day 15 in Cycle 3 and all subsequent cycles, until the participant no longer received clinical benefit. Rituximab 375 mg/m\^2 IV infusion was administered on Day 1 of each treatment cycle (maximum of 8 cycles), along with 90 mg/m\^2 IV infusion of bendamustine on Day 2 and Day 3 of each treatment cycle in Cycles 1 and 2. If the dose of bendamustine was well tolerated, then it was administered on Day 1 and Day 2 in Cycle 3 and all subsequent cycles for a maximum of 6 cycles. The duration of each treatment cycle was 28 days.
Concentration Verses Time Summary of Avelumab Cycle 1 Day 16	25.33 microgram per milliliter (mcg/mL) Standard Deviation 13.197	26.53 microgram per milliliter (mcg/mL) Standard Deviation 9.237	19.36 microgram per milliliter (mcg/mL) Standard Deviation 7.810
Concentration Verses Time Summary of Avelumab Cycle 1 Day 2	183.29 microgram per milliliter (mcg/mL) Standard Deviation 83.809	198.43 microgram per milliliter (mcg/mL) Standard Deviation 29.387	193.30 microgram per milliliter (mcg/mL) Standard Deviation 29.702
Concentration Verses Time Summary of Avelumab Cycle 1 Day 8	75.14 microgram per milliliter (mcg/mL) Standard Deviation 21.357	68.44 microgram per milliliter (mcg/mL) Standard Deviation 18.553	65.33 microgram per milliliter (mcg/mL) Standard Deviation 17.913
Concentration Verses Time Summary of Avelumab Cycle 4 Day 1	25.00 microgram per milliliter (mcg/mL) Standard Deviation 4.667	62.00 microgram per milliliter (mcg/mL) Standard Deviation NA Due to single participant with data available for this outcome measure at this time point, Standard Deviation was not estimable.	120.88 microgram per milliliter (mcg/mL) Standard Deviation 165.187
Concentration Verses Time Summary of Avelumab Cycle 6 Day 1	—	7.57 microgram per milliliter (mcg/mL) Standard Deviation NA Due to single participant with data available for this outcome measure at this time point, Standard Deviation was not estimable.	39.43 microgram per milliliter (mcg/mL) Standard Deviation 18.327

SECONDARY outcome

Timeframe: Baseline: 2 hours pre-dose of first dose of avelumab, Post baseline: post first dose up to up to 30 Days after the end of treatment (maximum up to 36 months)

Population: Avelumab immunogenicity analysis set included participants who had at least 1 ADA sample collected for avelumab.

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.