Safety and Efficacy Study of Loncastuximab Tesirine + Ibr... | NCT03684694

ID	Type	Description	Link
2018-002625-38	EudraCT Number

Label	Type	Description	Intervention Names
Phase 1: Dose-Escalation of ADCT-402	Experimental	A standard 3+3 dose escalation design will be used. The dose-limiting toxicity (DLT) period will be the 21 days following the first dose of ibrutinib. The dose escalation cohort will receive loncastuximab tesirine for Cycle 1 and 2 (3 weeks each) with concurrent ibrutinib (concomitant therapy) daily. Participants may continue to receive ibrutinib therapy up to 1 year after Cycle 1 Day 1 (once every 4 weeks from Cycle 3 onwards). Loncastuximab tesirine will be administered intravenously (IV).	Drug: Loncastuximab Tesirine Drug: Ibrutinib
Phase 2: MTD or RP2D of ADCT-402 in Non-GCB DLBCL	Experimental	Participants with non-germinal center B-cell diffuse large B-cell lymphoma (Non-GCB DLBCL) will receive the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of loncastuximab tesirine, as determined in Phase 1, once every 3 weeks for Cycle 1 and 2 and a daily dose of ibrutinib. Participants can continue treatment up to 1 year (once every 4 weeks from Cycle 3 onwards). Loncastuximab tesirine will be administered IV.	Drug: Loncastuximab Tesirine Drug: Ibrutinib
Phase 2: MTD or RP2D of ADCT-402 in GCB DLBCL	Experimental	Participants with germinal center B-cell diffuse large B-cell lymphoma (GCB DLBCL) will receive the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of loncastuximab tesirine, as determined in Phase 1, once every 3 weeks for Cycle 1 and 2 and a daily dose of ibrutinib. Participants can continue treatment up to 1 year (once every 4 weeks from Cycle 3 onwards). Loncastuximab tesirine will be administered IV.	Drug: Loncastuximab Tesirine Drug: Ibrutinib

Name	Type	Description	Arm Group Labels	Other Names
Loncastuximab Tesirine	Drug	Intravenous (IV) infusion.	Phase 1: Dose-Escalation of ADCT-402 Phase 2: MTD or RP2D of ADCT-402 in GCB DLBCL Phase 2: MTD or RP2D of ADCT-402 in MCL

Measure	Description	Time Frame
Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs)	A TEAE was defined as an adverse event (AE) that occurred or worsened in the period extending from the first dose of study drug to 30 days after the last dose of study drug in this study or start of a new anticancer therapy, whichever is earlier. Any clinically significant changes form baseline in safety laboratory values, vital signs, Eastern Cooperative Oncology Group (ECOG) performance status, and 12-lead electrocardiograms (ECGs) which occurred after first dose of study drug were recorded as TEAEs.	Day 1 until 30 days after last dose; max duration of treatment was 686 days for Phase 1 (up to approximately 716 days total)
Phase 1: Number of Participants With Serious TEAEs	A serious TEAE was defined as any AE which occurred after the first dose of study drug that resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization (hospitalization for elective procedures or for protocol compliance was not considered a serious adverse event), resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or important medical events that did not meet the preceding criteria but based on appropriate medical judgement may have jeopardized the participant or may have required medical or surgical intervention to prevent any of the outcomes listed above.	Day 1 until 30 days after last dose; max duration of treatment was 686 days for Phase 1 (up to approximately 716 days total)
Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs)	A DLT was defined as any of the following events which occur during the DLT Period (first 21 days of ibrutinib treatment), except those that are clearly due to underlying disease or extraneous causes: a hematologic DLT (grade ≥3 anaemia, grade 4/febrile neutropenia, grade ≥3 thrombocytopenia), a non-hematologic DLT (including aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT] >3× upper limit of normal (ULN) and bilirubin >2× ULN), any other non-hematologic toxicities ≥ Grade 3, with exceptions.	21 days

Measure	Description	Time Frame
Phase 1: Overall Response Rate (ORR)	ORR according to the 2014 Lugano classification, defined as the percentage of participants with a BOR of CR or partial response (PR).	Up to approximately 38 months
Phase 1 and Phase 2: Duration of Response (DOR)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female participant aged 18 years or older
Pathologic diagnosis of DLBCL or MCL (For Italy Sites Only: MCL patients are excluded.)
Participants with DLBCL must have relapsed or refractory disease and have failed or been intolerant to available standard therapy
Participants with MCL must have relapsed or refractory disease and have received at least one prior line of therapy (For Italy Sites Only: This exclusion criterion is not applicable)
Participants who have received previous CD19-directed therapy must have a biopsy which shows CD19 expression after completion of the CD19-directed therapy
Measurable disease as defined by the 2014 Lugano Classification
Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block (or minimum 10 freshly cut unstained slides if block is not available)
ECOG performance status 0 to 2
Screening laboratory values within the following parameters:
1. Absolute neutrophil count (ANC) ≥1.0 × 103/µL (off growth factors at least 72 hours)
2. Platelet count ≥75 × 103/µL without transfusion in the past 7 days
3. Hemoglobin ≥8 g/dL (4.96 mmol/L), transfusion allowed
4. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) ≤2.5 × the ULN
5. Total bilirubin ≤1.5 × ULN (participants with known Gilbert's syndrome may have a total bilirubin up to ≤3 × ULN)
6. Blood creatinine ≤1.5 × ULN or calculated creatinine clearance ≥60 mL/min by the Cockcroft and Gault equation
Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 7 days prior to start of study drugs on C1D1 for women of childbearing potential
Women of childbearing potential must agree to use a highly effective method of contraception from the time of giving informed consent until at least 9 months after the last dose of loncastuximab tesirine or 1 month after last dose of ibrutinib, whichever comes last. Men with female partners who are of childbearing potential must agree that they will use a highly effective method of contraception from the time of giving informed consent until at least 6 months after the participant receives his last dose of loncastuximab tesirine or 3 months after last dose of ibrutinib, whichever comes last

Exclusion Criteria:

Known history of hypersensitivity to or positive serum human anti-drug antibody (ADA) to a CD19 antibody
Known history of hypersensitivity to ibrutinib
Previous therapy with ibrutinib or other BTK inhibitors
Previous therapy with loncastuximab tesirine
Requires treatment or prophylaxis with a moderate or strong cytochrome P450 (CYP) 3A inhibitor
Allogenic or autologous transplant within 60 days prior to start of study drugs (C1D1)
Active graft-versus-host disease
Post-transplantation lymphoproliferative disorder
Active autoimmune disease, including motor neuropathy considered of autoimmune origin and other central nervous system (CNS) autoimmune disease
Known seropositive and requiring anti-viral therapy for human immunodeficiency (HIV) virus, hepatitis B virus (HBV), or hepatitis C virus (HCV).
History of Stevens-Johnson syndrome or toxic epidermal necrolysis
Lymphoma with active CNS involvement at the time of screening, including leptomeningeal disease
Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath)
Breastfeeding or pregnant
Significant medical comorbidities, including but not limited to, uncontrolled hypertension (blood pressure [BP] ≥160/100 millimeters of mercury (mmHg) repeatedly), unstable angina, congestive heart failure (greater than New York Heart Association class II), electrocardiographic evidence of acute ischemia, coronary angioplasty or myocardial infarction within 6 months prior to screening, uncontrolled atrial or ventricular cardiac arrhythmia, poorly controlled diabetes mellitus, or severe chronic pulmonary disease, or tuberculosis infection (tuberculosis screening based on local standards).
Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy within 14 days prior to start of study drugs (C1D1), except shorter if approved by the Sponsor
Use of any other experimental medication within 14 days prior to start of study drugs (C1D1)
Planned live vaccine administration after starting study drugs (C1D1)
Any condition that could interfere with the absorption or metabolism of ibrutinib including malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel
Inherited or acquired bleeding disorders
Ongoing anticoagulation treatment, except for low-dose heparinisation or equivalent
Failure to recover to Grade ≤1 (Common Terminology Criteria for Adverse Events [CTCAE] version 4.0) from acute non-hematologic toxicity (Grade ≤2 neuropathy or alopecia) due to previous therapy prior to screening
Congenital long QT syndrome or a corrected QTcF interval of >480 ms at screening (unless secondary to pacemaker or bundle branch block)
Active second primary malignancy other than non-melanoma skin cancers, non metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy that the Sponsor's medical monitor and Investigator agree, and document should not be exclusionary
Any other significant medical illness, abnormality, or condition that would, in the Investigator's judgement, make the participant inappropriate for study participation or put the participant at risk

Facility	Status	City	State	ZIP	Country	Contacts
University of California Irvine Health Chao Family Comprehensive Cancer Center		Orange	California	92868	United States

ID	Title	Description
FG000	Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced diffuse large B-Cell lymphoma (DLBCL) or mantle cell lymphoma (MCL) were enrolled to receive 60 µg/kg of loncastuximab tesirine via intravenous (IV) infusion once every 3 weeks (Q3W) for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 31, 2021	Nov 17, 2023

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

A TEAE was defined as an adverse event (AE) that occurred or worsened in the period extending from the first dose of study drug to 30 days after the last dose of study drug in this study or start of a new anticancer therapy, whichever is earlier. Any clinically significant changes form baseline in safety laboratory values, vital signs, Eastern Cooperative Oncology Group (ECOG) performance status, and 12-lead electrocardiograms (ECGs) which occurred after first dose of study drug were recorded as TEAEs.

Measured in the safety population, which included all participants who received study drug.

Posted

Count of Participants

Participants

Day 1 until 30 days after last dose; max duration of treatment was 686 days for Phase 1 (up to approximately 716 days total)

ID	Title	Description
OG000	Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced diffuse large B-Cell lymphoma (DLBCL) or mantle cell lymphoma (MCL) were enrolled to receive 60 µg/kg of loncastuximab tesirine via intravenous (IV) infusion once every 3 weeks (Q3W) for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6.
OG001	Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced DLBCL or MCL were enrolled to receive 75 µg/kg of loncastuximab tesirine via IV infusion Q3W for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6.
OG002	Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced DLBCL or MCL were enrolled to receive 90 µg/kg of loncastuximab tesirine via IV infusion Q3W for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6.

Units	Counts
Participants	OG00037 OG0014 OG0026

Title

Denominators

Categories

Title	Measurements
	OG00037 OG0014 OG0026

Primary

Phase 1: Number of Participants With Serious TEAEs

A serious TEAE was defined as any AE which occurred after the first dose of study drug that resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization (hospitalization for elective procedures or for protocol compliance was not considered a serious adverse event), resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or important medical events that did not meet the preceding criteria but based on appropriate medical judgement may have jeopardized the participant or may have required medical or surgical intervention to prevent any of the outcomes listed above.

Measured in the safety population, which included all participants who received study drug.

Posted

Count of Participants

Participants

Day 1 until 30 days after last dose; max duration of treatment was 686 days for Phase 1 (up to approximately 716 days total)

ID	Title	Description
OG000	Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced diffuse large B-Cell lymphoma (DLBCL) or mantle cell lymphoma (MCL) were enrolled to receive 60 µg/kg of loncastuximab tesirine via intravenous (IV) infusion once every 3 weeks (Q3W) for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6.

Primary

Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs)

A DLT was defined as any of the following events which occur during the DLT Period (first 21 days of ibrutinib treatment), except those that are clearly due to underlying disease or extraneous causes: a hematologic DLT (grade ≥3 anaemia, grade 4/febrile neutropenia, grade ≥3 thrombocytopenia), a non-hematologic DLT (including aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT] >3× upper limit of normal (ULN) and bilirubin >2× ULN), any other non-hematologic toxicities ≥ Grade 3, with exceptions.

Measured in the safety population, which included all participants who received study drug.

Posted

Count of Participants

Participants

21 days

ID	Title	Description
OG000	Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced diffuse large B-Cell lymphoma (DLBCL) or mantle cell lymphoma (MCL) were enrolled to receive 60 µg/kg of loncastuximab tesirine via intravenous (IV) infusion once every 3 weeks (Q3W) for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6.
OG001	Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced DLBCL or MCL were enrolled to receive 75 µg/kg of loncastuximab tesirine via IV infusion Q3W for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6.

Primary

Phase 1: Number of Participants With Dose Interruptions

Measured in the safety population, which included all participants who received study drug.

Posted

Count of Participants

Participants

Up to a maximum of 686 days

ID	Title	Description
OG000	Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced diffuse large B-Cell lymphoma (DLBCL) or mantle cell lymphoma (MCL) were enrolled to receive 60 µg/kg of loncastuximab tesirine via intravenous (IV) infusion once every 3 weeks (Q3W) for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6.
OG001	Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced DLBCL or MCL were enrolled to receive 75 µg/kg of loncastuximab tesirine via IV infusion Q3W for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6.
OG002

Primary

Phase 1: Number of Participants With Dose Reductions

Measured in the safety population, which included all participants who received study drug.

Posted

Count of Participants

Participants

Up to a maximum of 686 days

ID	Title	Description
OG000	Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced diffuse large B-Cell lymphoma (DLBCL) or mantle cell lymphoma (MCL) were enrolled to receive 60 µg/kg of loncastuximab tesirine via intravenous (IV) infusion once every 3 weeks (Q3W) for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6.
OG001	Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced DLBCL or MCL were enrolled to receive 75 µg/kg of loncastuximab tesirine via IV infusion Q3W for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6.
OG002

Primary

Phase 2: Complete Response Rate (CRR)

CRR according to the 2014 Lugano classifications determined by Independent Review Committee (IRC). CRR was defined as the percentage of participants with a best overall response (BOR) of complete response (CR).

Measured in the efficacy analysis set, which included all participants who received at least 1 dose of study drug, who had valid baseline disease assessment(s), and who had at least one valid post-baseline disease assessment. Participants who did not have a post-baseline assessment due to early clinical progression or death (after receiving study drug) were also included.

Posted

Number

95% Confidence Interval

percentage of participants

Up to approximately 38 months

ID	Title	Description
OG000	Phase 2: Loncastuximab Tesirine and Ibrutinib in Non-Germinal Center B-cell (GCB) DLBCL	Participants with non-germinal center B-cell (GCB) DLBCL received the recommended phase 2 dose (RP2D) of 60 µg/kg loncastuximab tesirine via IV infusion with concurrent 560 mg ibrutinib orally via capsules once daily. Loncastuximab tesirine was administered on Day 1 of Cycles 1 and 2 (cycle is 3 weeks for Cycles 1 and 2, and 4 weeks for Cycles 3 onwards). Participants who had a response of complete response (CR), partial response (PR), and stable disease (SD) received additional doses of loncastuximab tesirine on Day 1 of Cycles 5, 6, 9 and 10.
OG001	Phase 2: Loncastuximab Tesirine and Ibrutinib in GCB DLBCL

Secondary

Phase 1: Overall Response Rate (ORR)

ORR according to the 2014 Lugano classification, defined as the percentage of participants with a BOR of CR or partial response (PR).

Posted

Number

95% Confidence Interval

percentage of participants

Up to approximately 38 months

ID	Title	Description
OG000	Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced diffuse large B-Cell lymphoma (DLBCL) or mantle cell lymphoma (MCL) were enrolled to receive 60 µg/kg of loncastuximab tesirine via intravenous (IV) infusion once every 3 weeks (Q3W) for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6.
OG001	Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced DLBCL or MCL were enrolled to receive 75 µg/kg of loncastuximab tesirine via IV infusion Q3W for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6.

Secondary

Phase 1 and Phase 2: Duration of Response (DOR)

DOR was defined as the time from the first documentation of tumor response to disease progression or death.

Measured in the efficacy analysis set, which included all participants who received at least 1 dose of study drug, who had valid baseline disease assessment(s), who had at least one valid post-baseline disease assessment who achieved a response. Participants who did not have a post-baseline assessment due to early clinical progression or death (after receiving study drug) were also included.

Posted

Median

95% Confidence Interval

months

Up to approximately 36 months

ID	Title	Description
OG000	Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced diffuse large B-Cell lymphoma (DLBCL) or mantle cell lymphoma (MCL) were enrolled to receive 60 µg/kg of loncastuximab tesirine via intravenous (IV) infusion once every 3 weeks (Q3W) for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6.
OG001	Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced DLBCL or MCL were enrolled to receive 75 µg/kg of loncastuximab tesirine via IV infusion Q3W for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6.

Secondary

Phase 1 and Phase 2: Relapse-Free Survival (RFS)

RFS was defined as the time from the documentation of CR to disease progression or death.

Measured in the efficacy analysis set, which included all participants who received at least 1 dose of study drug, who had valid baseline disease assessment(s), and who had at least one valid post-baseline disease assessment who achieved CR. Participants who did not have a post-baseline assessment due to early clinical progression or death (after receiving study drug) were also included.

Posted

Median

95% Confidence Interval

months

Up to approximately 36 months

ID	Title	Description
OG000	Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced diffuse large B-Cell lymphoma (DLBCL) or mantle cell lymphoma (MCL) were enrolled to receive 60 µg/kg of loncastuximab tesirine via intravenous (IV) infusion once every 3 weeks (Q3W) for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6.
OG001	Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced DLBCL or MCL were enrolled to receive 75 µg/kg of loncastuximab tesirine via IV infusion Q3W for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6.

Secondary

Phase 1 and Phase 2: Progression-Free Survival (PFS)

PFS was defined as the time between start of treatment and the first documentation of progression, or death.

Posted

Median

95% Confidence Interval

months

Up to approximately 37 months

ID	Title	Description
OG000	Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced diffuse large B-Cell lymphoma (DLBCL) or mantle cell lymphoma (MCL) were enrolled to receive 60 µg/kg of loncastuximab tesirine via intravenous (IV) infusion once every 3 weeks (Q3W) for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6.
OG001	Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced DLBCL or MCL were enrolled to receive 75 µg/kg of loncastuximab tesirine via IV infusion Q3W for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6.

Secondary

Phase 1 and Phase 2: Overall Survival (OS)

OS was defined as the time between the start of treatment and death from any cause.

Posted

Median

95% Confidence Interval

months

Up to approximately 38 months

ID	Title	Description
OG000	Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced diffuse large B-Cell lymphoma (DLBCL) or mantle cell lymphoma (MCL) were enrolled to receive 60 µg/kg of loncastuximab tesirine via intravenous (IV) infusion once every 3 weeks (Q3W) for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6.
OG001	Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced DLBCL or MCL were enrolled to receive 75 µg/kg of loncastuximab tesirine via IV infusion Q3W for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6.

Secondary

Phase 1 and Phase 2: Time to Reach Maximum Concentration (Tmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199)

Blood samples were collected for analysis of PK data of loncastuximab tesirine (total antibody, PBD-conjugated antibody and unconjugated cytotoxin SG3199)

Measured in the PK population, which included all participants who had at least 1 pre-C1D1 and 1 post-dose valid PK assessment. The "number of participants analzyed" represents the number of participants with collected data. Analysis reported per dose of loncastuximab tesirine as pre-specified.

Posted

Geometric Mean

Geometric Coefficient of Variation

days

C1D1 pre-dose, EOI, 4h PD, C1D8 168h PD, C1D15 336h PD, C2D1 pre-dose, EOI, 4h PD, C2D8 168h PD, C2D15 336h PD (3 week cycles)

ID	Title	Description
OG000	Phase 1 and Phase 2: 60 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced diffuse large B-Cell lymphoma (DLBCL) or mantle cell lymphoma (MCL) were enrolled to receive 60 µg/kg of loncastuximab tesirine via intravenous (IV) infusion once every 3 weeks (Q3W) for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants in Phase 1 who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6. Participants in Phase 2 who had a response of complete response (CR), partial response (PR), and stable disease (SD) received additional doses of loncastuximab tesirine on Day 1 of Cycles 5, 6, 9 and 10.

Secondary

Phase 1 and Phase 2: Maximum Observed Concentration (Cmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199)

Blood samples were collected for analysis of PK data of loncastuximab tesirine (total antibody, PBD-conjugated antibody and unconjugated cytotoxin SG3199)

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

C1D1 pre-dose, EOI, 4h PD, C1D8 168h PD, C1D15 336h PD, C2D1 pre-dose, EOI, 4h PD, C2D8 168h PD, C2D15 336h PD (3 week cycles)

ID	Title	Description
OG000	Phase 1 and Phase 2: 60 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced diffuse large B-Cell lymphoma (DLBCL) or mantle cell lymphoma (MCL) were enrolled to receive 60 µg/kg of loncastuximab tesirine via intravenous (IV) infusion once every 3 weeks (Q3W) for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants in Phase 1 who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6. Participants in Phase 2 who had a response of complete response (CR), partial response (PR), and stable disease (SD) received additional doses of loncastuximab tesirine on Day 1 of Cycles 5, 6, 9 and 10.

Secondary

Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199)

Blood samples were collected for analysis of PK data of loncastuximab tesirine (total antibody, PBD-conjugated antibody and unconjugated cytotoxin SG3199)

Posted

Geometric Mean

Geometric Coefficient of Variation

day*ng/mL

C1D1 pre-dose, EOI, 4h PD, C1D8 168h PD, C1D15 336h PD, C2D1 pre-dose, EOI, 4h PD, C2D8 168h PD, C2D15 336h PD (3 week cycles)

ID	Title	Description
OG000	Phase 1 and Phase 2: 60 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced diffuse large B-Cell lymphoma (DLBCL) or mantle cell lymphoma (MCL) were enrolled to receive 60 µg/kg of loncastuximab tesirine via intravenous (IV) infusion once every 3 weeks (Q3W) for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants in Phase 1 who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6. Participants in Phase 2 who had a response of complete response (CR), partial response (PR), and stable disease (SD) received additional doses of loncastuximab tesirine on Day 1 of Cycles 5, 6, 9 and 10.

Secondary

Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the End of the Dosing Interval (AUCtau) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199)

Blood samples were collected for analysis of PK data of loncastuximab tesirine (total antibody, PBD-conjugated antibody and unconjugated cytotoxin SG3199).

Posted

Geometric Mean

Geometric Coefficient of Variation

day*ng/mL

C1D1 pre-dose, EOI, 4h PD, C1D8 168h PD, C1D15 336h PD, C2D1 pre-dose, EOI, 4h PD, C2D8 168h PD, C2D15 336h PD (3 week cycles)

ID	Title	Description
OG000	Phase 1 and Phase 2: 60 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced diffuse large B-Cell lymphoma (DLBCL) or mantle cell lymphoma (MCL) were enrolled to receive 60 µg/kg of loncastuximab tesirine via intravenous (IV) infusion once every 3 weeks (Q3W) for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants in Phase 1 who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6. Participants in Phase 2 who had a response of complete response (CR), partial response (PR), and stable disease (SD) received additional doses of loncastuximab tesirine on Day 1 of Cycles 5, 6, 9 and 10.

Secondary

Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199)

Blood samples were collected for analysis of PK data of loncastuximab tesirine (total antibody, PBD-conjugated antibody and unconjugated cytotoxin SG3199).

Posted

Geometric Mean

Geometric Coefficient of Variation

day*ng/mL

C1D1 pre-dose, EOI, 4h PD, C1D8 168h PD, C1D15 336h PD, C2D1 pre-dose, EOI, 4h PD, C2D8 168h PD, C2D15 336h PD (3 week cycles)

ID	Title	Description
OG000	Phase 1 and Phase 2: 60 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced diffuse large B-Cell lymphoma (DLBCL) or mantle cell lymphoma (MCL) were enrolled to receive 60 µg/kg of loncastuximab tesirine via intravenous (IV) infusion once every 3 weeks (Q3W) for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants in Phase 1 who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6. Participants in Phase 2 who had a response of complete response (CR), partial response (PR), and stable disease (SD) received additional doses of loncastuximab tesirine on Day 1 of Cycles 5, 6, 9 and 10.

Secondary

Phase 1 and Phase 2: Clearance (CL) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199)

Blood samples were collected for analysis of PK data of loncastuximab tesirine (total antibody, PBD-conjugated antibody and unconjugated cytotoxin SG3199).

Posted

Geometric Mean

Geometric Coefficient of Variation

L/day

C1D1 pre-dose, EOI, 4h PD, C1D8 168h PD, C1D15 336h PD, C2D1 pre-dose, EOI, 4h PD, C2D8 168h PD, C2D15 336h PD (3 week cycles)

ID	Title	Description
OG000	Phase 1 and Phase 2: 60 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced diffuse large B-Cell lymphoma (DLBCL) or mantle cell lymphoma (MCL) were enrolled to receive 60 µg/kg of loncastuximab tesirine via intravenous (IV) infusion once every 3 weeks (Q3W) for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants in Phase 1 who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6. Participants in Phase 2 who had a response of complete response (CR), partial response (PR), and stable disease (SD) received additional doses of loncastuximab tesirine on Day 1 of Cycles 5, 6, 9 and 10.

Secondary

Phase 1 and Phase 2: Accumulation Index (AI) Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199)

Blood samples were collected for analysis of PK data of loncastuximab tesirine (total antibody, PBD-conjugated antibody and unconjugated cytotoxin SG3199).

Posted

Geometric Mean

Geometric Coefficient of Variation

ratio

C1D1 pre-dose, EOI, 4h PD, C1D8 168h PD, C1D15 336h PD, C2D1 pre-dose, EOI, 4h PD, C2D8 168h PD, C2D15 336h PD (3 week cycles)

ID	Title	Description
OG000	Phase 1 and Phase 2: 60 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced diffuse large B-Cell lymphoma (DLBCL) or mantle cell lymphoma (MCL) were enrolled to receive 60 µg/kg of loncastuximab tesirine via intravenous (IV) infusion once every 3 weeks (Q3W) for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants in Phase 1 who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6. Participants in Phase 2 who had a response of complete response (CR), partial response (PR), and stable disease (SD) received additional doses of loncastuximab tesirine on Day 1 of Cycles 5, 6, 9 and 10.

Secondary

Phase 1 and Phase 2: Number of Participants With Positive Anti-Drug Antibody (ADA) Titers to Loncastuximab Tesirine at Any Time

Detection of ADAs was performed by using a screening assay for identification of antibody positive samples/participants, a confirmation assay, and titer assessment.

ADA-evaluable participants including all participants tested for ADAs in the study.

Posted

Count of Participants

Participants

Up to a maximum of 711 days

ID	Title	Description
OG000	Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced diffuse large B-Cell lymphoma (DLBCL) or mantle cell lymphoma (MCL) were enrolled to receive 60 µg/kg of loncastuximab tesirine via intravenous (IV) infusion once every 3 weeks (Q3W) for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6.
OG001	Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced DLBCL or MCL were enrolled to receive 75 µg/kg of loncastuximab tesirine via IV infusion Q3W for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6.

Secondary

Phase 2: ORR

ORR according to the 2014 Lugano classification, defined as the percentage of participants with a BOR of CR or PR.

Posted

Number

95% Confidence Interval

percentage of participants

Up to approximately 38 months

ID	Title	Description
OG000	Phase 2: Loncastuximab Tesirine and Ibrutinib in Non-Germinal Center B-cell (GCB) DLBCL	Participants with non-germinal center B-cell (GCB) DLBCL received the recommended phase 2 dose (RP2D) of 60 µg/kg loncastuximab tesirine via IV infusion with concurrent 560 mg ibrutinib orally via capsules once daily. Loncastuximab tesirine was administered on Day 1 of Cycles 1 and 2 (cycle is 3 weeks for Cycles 1 and 2, and 4 weeks for Cycles 3 onwards). Participants who had a response of complete response (CR), partial response (PR), and stable disease (SD) received additional doses of loncastuximab tesirine on Day 1 of Cycles 5, 6, 9 and 10.
OG001	Phase 2: Loncastuximab Tesirine and Ibrutinib in GCB DLBCL	Participants with GCB DLBCL received the RP2D of 60 µg/kg loncastuximab tesirine via IV infusion with concurrent 560 mg ibrutinib orally via capsules once daily. Loncastuximab tesirine was administered on Day 1 of Cycles 1 and 2 (cycle is 3 weeks for Cycles 1 and 2, and 4 weeks for Cycles 3 onwards). Participants who had a response of CR, PR, and SD received additional doses of loncastuximab tesirine on Day 1 of Cycles 5, 6, 9 and 10.

Secondary

Phase 2: CRR in Non-GCB DLBCL, GCB DLBCL, All DLBCL and MCL Participants

CRR according to the 2014 Lugano classifications determined by the IRC. CRR was defined as the percentage of participants with a BOR of CR in non-GCB DLBCL, GCB DLBCL, all DLBCL, and MCL participants.

Posted

Number

95% Confidence Interval

percentage of participants

Up to approximately 38 months

ID	Title	Description
OG000	Phase 2: Loncastuximab Tesirine and Ibrutinib in Non-Germinal Center B-cell (GCB) DLBCL	Participants with non-germinal center B-cell (GCB) DLBCL received the recommended phase 2 dose (RP2D) of 60 µg/kg loncastuximab tesirine via IV infusion with concurrent 560 mg ibrutinib orally via capsules once daily. Loncastuximab tesirine was administered on Day 1 of Cycles 1 and 2 (cycle is 3 weeks for Cycles 1 and 2, and 4 weeks for Cycles 3 onwards). Participants who had a response of complete response (CR), partial response (PR), and stable disease (SD) received additional doses of loncastuximab tesirine on Day 1 of Cycles 5, 6, 9 and 10.
OG001	Phase 2: Loncastuximab Tesirine and Ibrutinib in GCB DLBCL

Secondary

Phase 2: Number of Participants With TEAEs

A TEAE was defined as an adverse event (AE) that occurred or worsened in the period extending from the first dose of study drug to 30 days after the last dose of study drug in this study or start of a new anticancer therapy, whichever is earlier. Any clinically significant changes form baseline in safety laboratory values, vital signs, ECOG performance status, and 12-lead ECGs which occurred after first dose of study drug were recorded as TEAEs.

Measured in the safety population, which included all participants who received study drug.

Posted

Count of Participants

Participants

Day 1 until 30 days after last dose; max duration of treatment was 711 days for Phase 2 (up to approximately 741 days total)

ID	Title	Description
OG000	Phase 2: Loncastuximab Tesirine and Ibrutinib in Non-Germinal Center B-cell (GCB) DLBCL	Participants with non-germinal center B-cell (GCB) DLBCL received the recommended phase 2 dose (RP2D) of 60 µg/kg loncastuximab tesirine via IV infusion with concurrent 560 mg ibrutinib orally via capsules once daily. Loncastuximab tesirine was administered on Day 1 of Cycles 1 and 2 (cycle is 3 weeks for Cycles 1 and 2, and 4 weeks for Cycles 3 onwards). Participants who had a response of complete response (CR), partial response (PR), and stable disease (SD) received additional doses of loncastuximab tesirine on Day 1 of Cycles 5, 6, 9 and 10.
OG001	Phase 2: Loncastuximab Tesirine and Ibrutinib in GCB DLBCL

Secondary

Phase 2: Number of Participants With Serious TEAEs

Measured in the safety population, which included all participants who received study drug.

Posted

Count of Participants

Participants

Day 1 until 30 days after last dose; max duration of treatment was 711 days for Phase 2 (up to approximately 741 days total)

ID	Title	Description
OG000	Phase 2: Loncastuximab Tesirine and Ibrutinib in Non-Germinal Center B-cell (GCB) DLBCL	Participants with non-germinal center B-cell (GCB) DLBCL received the recommended phase 2 dose (RP2D) of 60 µg/kg loncastuximab tesirine via IV infusion with concurrent 560 mg ibrutinib orally via capsules once daily. Loncastuximab tesirine was administered on Day 1 of Cycles 1 and 2 (cycle is 3 weeks for Cycles 1 and 2, and 4 weeks for Cycles 3 onwards). Participants who had a response of complete response (CR), partial response (PR), and stable disease (SD) received additional doses of loncastuximab tesirine on Day 1 of Cycles 5, 6, 9 and 10.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Neutropenia	Blood and lymphatic system disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG0030 affected49 at risk EG0040 affected30 at risk EG0050 affected10 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Lymph node pain	Blood and lymphatic system disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Haemorrhagic disorder	Blood and lymphatic system disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Pericardial effusion	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Cardiomyopathy	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Cardiopulmonary failure	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Coronary artery disease	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Pericardial disease	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Pericarditis	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Inappropriate antidiuretic hormone secretion	Endocrine disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Pneumatosis intestinalis	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Death	General disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Asthenia	General disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Oedema peripheral	General disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
General physical health deterioration	General disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Disease progression	General disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Cholecystitis acute	Hepatobiliary disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Corona virus infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Citrobacter infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Enterococcal infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Folliculitis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Pneumocystis jirovecii infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Pneumonia	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Pneumonia fungal	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Progressive multifocal leukoencephalopathy	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Urinary tract infection bacterial	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Pneumonia viral	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Sepsis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Bacteraemia	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Campylobacter infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Escherichia sepsis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Pneumonia parainfluenzae viral	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Urosepsis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Humerus fracture	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Transaminases increased	Investigations	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Bone swelling	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Tumour associated fever	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Ataxia	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Delirium	Psychiatric disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Renal failure	Renal and urinary disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Hypotension	Vascular disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Drug reaction with eosinophilia and systemic symptoms	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 22.0	Systematic Assessment	EG00017 affected37 at risk EG0012 affected4 at risk EG0024 affected6 at risk EG00322 affected49 at risk EG00412 affected30 at risk EG0054 affected10 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 22.0	Systematic Assessment	EG0009 affected37 at risk EG0012 affected4 at risk EG0024 affected6 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 22.0	Systematic Assessment	EG0005 affected37 at risk EG0013 affected4 at risk EG0021 affected6 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0011 affected4 at risk EG0021 affected6 at risk EG003
Lymphopenia	Blood and lymphatic system disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Sinus bradycardia	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Tachycardia	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Palpitations	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Acute coronary syndrome	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Bradycardia	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA 22.0	Systematic Assessment	EG0003 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Swelling of eyelid	Eye disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Vision blurred	Eye disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Ocular hyperaemia	Eye disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Cataract	Eye disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0009 affected37 at risk EG0012 affected4 at risk EG0021 affected6 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0009 affected37 at risk EG0011 affected4 at risk EG0021 affected6 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0004 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0003 affected37 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0003 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Faeces soft	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Pancreatitis	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Odynophagia	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Oral pain	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Fatigue	General disorders	MedDRA 22.0	Systematic Assessment	EG0009 affected37 at risk EG0010 affected4 at risk EG0022 affected6 at risk EG003
Oedema peripheral	General disorders	MedDRA 22.0	Systematic Assessment	EG0006 affected37 at risk EG0011 affected4 at risk EG0021 affected6 at risk EG003
Asthenia	General disorders	MedDRA 22.0	Systematic Assessment	EG0006 affected37 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Pyrexia	General disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0022 affected6 at risk EG003
Chills	General disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Early satiety	General disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Malaise	General disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Mucosal inflammation	General disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Pain	General disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Sensation of foreign body	General disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Peripheral swelling	General disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Chest pain	General disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Generalised oedema	General disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Hepatocellular injury	Hepatobiliary disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Bile duct stone	Hepatobiliary disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Cholecystocholangitis	Hepatobiliary disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Hypogammaglobulinaemia	Immune system disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Conjunctivitis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0006 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0003 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Pneumonia	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0003 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Corona virus infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Furuncle	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Sinusitis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Herpes zoster	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Lung infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Oral fungal infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Pharyngitis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Rhinitis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Bronchitis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Eye infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Oral herpes	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Clostridium difficile colitis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Erysipelas	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Genital infection fungal	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Skin abrasion	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Limb injury	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 22.0	Systematic Assessment	EG0003 affected37 at risk EG0010 affected4 at risk EG0023 affected6 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA 22.0	Systematic Assessment	EG0004 affected37 at risk EG0010 affected4 at risk EG0022 affected6 at risk EG003
Lipase increased	Investigations	MedDRA 22.0	Systematic Assessment	EG0003 affected37 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Weight increased	Investigations	MedDRA 22.0	Systematic Assessment	EG0004 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Weight decreased	Investigations	MedDRA 22.0	Systematic Assessment	EG0003 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Amylase increased	Investigations	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Blood creatinine increased	Investigations	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Blood iron decreased	Investigations	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0011 affected4 at risk EG0022 affected6 at risk EG003
Coronavirus test positive	Investigations	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0006 affected37 at risk EG0011 affected4 at risk EG0021 affected6 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0005 affected37 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0005 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0004 affected37 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0004 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0011 affected4 at risk EG0021 affected6 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0003 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Hypermagnesaemia	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0003 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0003 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Musculoskeletal pain	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Headache	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Dizziness	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Ataxia	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 22.0	Systematic Assessment	EG0004 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 22.0	Systematic Assessment	EG0003 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Agitation	Psychiatric disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Depression	Psychiatric disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Confusional state	Psychiatric disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0006 affected37 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Dry throat	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0007 affected37 at risk EG0011 affected4 at risk EG0021 affected6 at risk EG003
Dermatitis bullous	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0004 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0003 affected37 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0003 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Petechiae	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0003 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Photosensitivity reaction	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Blister	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Purpura	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Onychoclasis	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Blood blister	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Lividity	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Macule	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Palmar erythema	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Rash macular	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Rash vesicular	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Hypertension	Vascular disorders	MedDRA 22.0	Systematic Assessment	EG0004 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Haematoma	Vascular disorders	MedDRA 22.0	Systematic Assessment	EG0003 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Flushing	Vascular disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Phlebitis	Vascular disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003

ID	Term
D016403	Lymphoma, Large B-Cell, Diffuse
D020522	Lymphoma, Mantle-Cell

ID	Term
D016393	Lymphoma, B-Cell
D008228	Lymphoma, Non-Hodgkin
D008223	Lymphoma
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D006425	Hemic and Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases

ID	Title	Description
BG000	Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced diffuse large B-Cell lymphoma (DLBCL) or mantle cell lymphoma (MCL) were enrolled to receive 60 µg/kg of loncastuximab tesirine via intravenous (IV) infusion once every 3 weeks (Q3W) for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6.
BG001	Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced DLBCL or MCL were enrolled to receive 75 µg/kg of loncastuximab tesirine via IV infusion Q3W for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6.
BG002	Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced DLBCL or MCL were enrolled to receive 90 µg/kg of loncastuximab tesirine via IV infusion Q3W for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6.
BG003	Phase 2: Loncastuximab Tesirine and Ibrutinib in Non-Germinal Center B-cell (GCB) DLBCL	Participants with non-germinal center B-cell (GCB) DLBCL received the recommended phase 2 dose (RP2D) of 60 µg/kg loncastuximab tesirine via IV infusion with concurrent 560 mg ibrutinib orally via capsules once daily. Loncastuximab tesirine was administered on Day 1 of Cycles 1 and 2 (cycle is 3 weeks for Cycles 1 and 2, and 4 weeks for Cycles 3 onwards). Participants who had a response of complete response (CR), partial response (PR), and stable disease (SD) received additional doses of loncastuximab tesirine on Day 1 of Cycles 5, 6, 9 and 10.
BG004	Phase 2: Loncastuximab Tesirine and Ibrutinib in GCB DLBCL	Participants with GCB DLBCL received the RP2D of 60 µg/kg loncastuximab tesirine via IV infusion with concurrent 560 mg ibrutinib orally via capsules once daily. Loncastuximab tesirine was administered on Day 1 of Cycles 1 and 2 (cycle is 3 weeks for Cycles 1 and 2, and 4 weeks for Cycles 3 onwards). Participants who had a response of CR, PR, and SD received additional doses of loncastuximab tesirine on Day 1 of Cycles 5, 6, 9 and 10.
BG005	Phase 2: Loncastuximab Tesirine and Ibrutinib in MCL	Participants with MCL received the RP2D of 60 µg/kg loncastuximab tesirine via IV infusion with concurrent 560 mg ibrutinib orally via capsules once daily. Loncastuximab tesirine was administered on Day 1 of Cycles 1 and 2 (cycle is 3 weeks for Cycles 1 and 2, and 4 weeks for Cycles 3 onwards). Participants who had a response of CR, PR, and SD received additional doses of loncastuximab tesirine on Day 1 of Cycles 5, 6, 9 and 10.
BG006	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced diffuse large B-Cell lymphoma (DLBCL) or mantle cell lymphoma (MCL) were enrolled to receive 60 µg/kg of loncastuximab tesirine via intravenous (IV) infusion once every 3 weeks (Q3W) for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6.	24	37	19	37	37	37
EG001	Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced DLBCL or MCL were enrolled to receive 75 µg/kg of loncastuximab tesirine via IV infusion Q3W for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6.	0	4	0	4	4	4
EG002	Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib	Participants with advanced DLBCL or MCL were enrolled to receive 90 µg/kg of loncastuximab tesirine via IV infusion Q3W for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6.	3	6	3	6	6	6
EG003	Phase 2: Loncastuximab Tesirine and Ibrutinib in Non-Germinal Center B-cell (GCB) DLBCL	Participants with non-germinal center B-cell (GCB) DLBCL received the recommended phase 2 dose (RP2D) of 60 µg/kg loncastuximab tesirine via IV infusion with concurrent 560 mg ibrutinib orally via capsules once daily. Loncastuximab tesirine was administered on Day 1 of Cycles 1 and 2 (cycle is 3 weeks for Cycles 1 and 2, and 4 weeks for Cycles 3 onwards). Participants who had a response of complete response (CR), partial response (PR), and stable disease (SD) received additional doses of loncastuximab tesirine on Day 1 of Cycles 5, 6, 9 and 10.	28	49	27	49	48	49
EG004	Phase 2: Loncastuximab Tesirine and Ibrutinib in GCB DLBCL	Participants with GCB DLBCL received the RP2D of 60 µg/kg loncastuximab tesirine via IV infusion with concurrent 560 mg ibrutinib orally via capsules once daily. Loncastuximab tesirine was administered on Day 1 of Cycles 1 and 2 (cycle is 3 weeks for Cycles 1 and 2, and 4 weeks for Cycles 3 onwards). Participants who had a response of CR, PR, and SD received additional doses of loncastuximab tesirine on Day 1 of Cycles 5, 6, 9 and 10.	14	30	5	30	30	30
EG005	Phase 2: Loncastuximab Tesirine and Ibrutinib in MCL	Participants with MCL received the RP2D of 60 µg/kg loncastuximab tesirine via IV infusion with concurrent 560 mg ibrutinib orally via capsules once daily. Loncastuximab tesirine was administered on Day 1 of Cycles 1 and 2 (cycle is 3 weeks for Cycles 1 and 2, and 4 weeks for Cycles 3 onwards). Participants who had a response of CR, PR, and SD received additional doses of loncastuximab tesirine on Day 1 of Cycles 5, 6, 9 and 10.	3	10	5	10	10	10