A Study of Loncastuximab Tesirine and Rituximab (Lonca-R)... | NCT05144009

NCT05144009

ID	Type	Description	Link
2021-005312-57	EudraCT Number
2022-501601-12-00	EU Trial (CTIS) Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Cohort A : Loncastuximab Tesirine + Rituximab (Lonca-R)	Experimental	Participants who are unfit (per sGA) will receive Lonca-R for 3 cycles. Participants who achieve a complete response (CR) will receive Lonca-R for 1 additional cycle. Participants who achieve a partial response (PR) will receive Lonca-R for 3 additional cycles. Lonca-R will be administered as rituximab 375 mg/m^2 on Day 1 of Cycle 1 and loncastuximab tesirine 150 µg/kg on Day 2 of Cycle 1. During Cycle 2, Lonca-R will be administered as rituximab* 375 mg/m^2 and loncastuximab tesirine 150 µg/kg on Day 1. For cycles 3 and beyond, Lonca-R will be administered as rituximab 375 mg/m^2 and loncastuximab tesirine 75 µg/kg on Day 1. *subcutaneous rituximab 1400mg/dose may be used during Cycle 2 and beyond	Drug: Loncastuximab Tesirine Drug: Rituximab
Cohort B : Loncastuximab Tesirine + Rituximab (Lonca-R)	Experimental	Participants who are frail (per sGA) or participants with cardiac comorbidities will receive Lonca-R for 3 cycles. Participants who achieve a CR will receive Lonca-R for 1 additional cycle. Participants who achieve a PR will receive Lonca-R for 3 additional cycles for a total of up to 6 cycles. Only participants enrolled in Cohort B, who achieve stable disease (SD) and deriving clinical benefit per the treating physician, may also receive Lonca-R for an additional 3 cycles. Lonca-R will be administered as rituximab 375 mg/m^2 on Day 1 of Cycle 1 and loncastuximab tesirine 150 µg/kg on Day 2 of Cycle 1. During Cycle 2, Lonca-R will be administered as rituximab* 375 mg/m^2 and loncastuximab tesirine 150 µg/kg on Day 1. For cycles 3 and beyond, Lonca-R will be administered as rituximab 375 mg/m^2 and loncastuximab tesirine 75 µg/kg on Day 1. *subcutaneous rituximab 1400mg/dose may be used during Cycle 2 and beyond	Drug: Loncastuximab Tesirine Drug: Rituximab

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Loncastuximab Tesirine	Drug	Intravenous (IV) Infusion	Cohort A : Loncastuximab Tesirine + Rituximab (Lonca-R) Cohort B : Loncastuximab Tesirine + Rituximab (Lonca-R)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
CR Rate	Defined as percentage of participants with a best overall response (BOR) of CR as determined by the Investigator according to the 2014 Lugano Classification criteria. CR was defined as achieving: Complete metabolic response for positron emission tomography (PET)-computed tomography (CT) OR Complete radiologic response (target node regress to <1.5 cm, no non-measured lesions, no organ enlargement, no new lesions and normal bone marrow morphology) for CT if disease was not fluorodeoxyglucose (FDG)-avid at baseline.	Up to a maximum of 17.1 months
Cohort B: Percentage of Participants Who Completed 4 Cycles of Treatment	Defined by the number of participants who completed a total of 4 cycles of therapy divided by the total number of participants * 100.	Up to 12 weeks (3 week cycle length)

Secondary Outcomes

Measure	Description	Time Frame
Overall Response Rate (ORR)	Defined as the percentage of participants who achieved either CR or PR as BOR as determined by Investigator according to the 2014 Lugano Classification criteria. CR was defined as achieving: Complete metabolic response for PET-CT OR Complete radiologic response (target node regress to <1.5 cm, no non-measured lesions, no organ enlargement, no new lesions and normal bone marrow morphology) for CT if disease was not FDG-avid at baseline. PR was defined as achieving: Partial metabolic response (findings indicate residual disease) for PET-CT OR Partial remission (>50% decrease in target measurable nodes, regression/ absence/ no increase of non-measured lesions, spleen regressed by >50% in length and no new lesions) for CT if disease was not FDG-avid at baseline.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Pathologic diagnosis of DLBCL, as defined by the 2016 World Health Organization (WHO) classification (including participants with DLBCL transformed from indolent lymphoma), or HGBCL, or Grade 3b FL.
Measurable disease as defined by the 2014 Lugano Classification.
Stages I-IV.
ECOG PS 0-2; ECOG PS 3 allowed if decline in status is deemed related to lymphoma & felt to be potentially reversible by the treating physician.
Adequate organ function as defined by screening laboratory values within the following parameters:
1. Absolute neutrophil count (ANC) ≥1.0 x 10^3/µL (off growth factors at least 72 hours).
2. Platelet count ≥75 x 10^3/µL without transfusion in the past 7 days.
3. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) ≤2.5 x the upper limit of normal (ULN).
4. Total bilirubin ≤1.5 x ULN (participants with known Gilbert's syndrome may have a total bilirubin up to ≤3 x ULN).
5. Calculated creatinine clearance >30 mL/min by the Cockcroft and Gault equation.

Note: A laboratory assessment may be repeated a maximum of two times during the screening period to confirm eligibility.

Women of childbearing potential (WOCBP) must agree to use a highly effective method of contraception from the time of giving informed consent until at least 12 months after the last dose of study treatment. Men with female partners who are of childbearing potential must agree to use a condom when sexually active or practice total abstinence from the time of the first dose until at least 7 months after the participant receives his last dose of study treatment.

Inclusion Criteria specific for Cohort A:

Unfit as defined by the simplified geriatric assessment (sGA). Includes all of the following:
1. Aged ≥80 years
2. ADL score of 6
3. IADL score of 8
4. CIRS-G: no score of 3-4 and <5 scores of 2

Inclusion Criteria specific for Cohort B:

Frail as defined by sGA:
1. Aged ≥80 years
2. ADL score of <6 and/or
3. IADL score of <8 and/or
4. CIRS-G: ≥1 score of 3-4 and/or >5 scores of 2 OR
Aged ≥65 - <80 with at least one of the following cardiac comorbidities that make anthracycline-containing regimens inadvisable as determined by the investigator.
1. Left ventricular ejection fraction (LVEF) ≥30 to <50%
2. History of myocardial infarction within 6 months prior to screening
3. Ischemic heart disease
4. History of stroke within 12 months prior to screening

Exclusion Criteria:

Known history of hypersensitivity to or positive serum human anti-drug antibody to a cluster of differentiation 19 (CD19) antibody.
Previous therapy for DLBCL, HGBCL, or Grade 3b FL (with exception of corticosteroid course for symptom management of less than 14 days).
Previous therapy with loncastuximab tesirine and rituximab for any indication.
Known history of hypersensitivity to any component of study treatment (loncastuximab tesirine and rituximab)
Human immunodeficiency virus (HIV) seropositive with any of the following:
1. CD4+ T-cell (CD4+) counts <350 cells/µL
2. Acquired immunodeficiency syndrome (AIDS) - defining opportunistic infection within 12 months prior to screening
3. Not on anti-retroviral therapy, or on anti-retroviral therapy for <4 weeks at the time of screening
4. HIV viral load ≥400 copies/mL
Serologic evidence of chronic hepatitis B virus (HBV) infection and unable or unwilling to receive standard prophylactic antiviral therapy or with detectable HBV viral load.
Serologic evidence of hepatitis C virus (HCV) infection without completion of curative treatment or with detectable HCV viral load.
History of Stevens-Johnson syndrome or toxic epidermal necrolysis.
Lymphoma with active central nervous system 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).
Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy within 14 days prior to start of study drug (Cycle 1 Day 1 [C1D1]), except shorter if approved by the Sponsor.
Use of any other experimental medication within 14 days prior to start of study drug (C1D1).
Received live vaccine within 4 weeks of C1D1.
Congenital long QT syndrome or a corrected Fridericia correction of the QT measure (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 judgment, make the participant inappropriate for study participation or put the participant at risk.

Contacts/Locations Module

Facility	Status	City	State	ZIP	Country	Contacts
University of Arizona Cancer Center		Tucson	Arizona	85724	United States
Winthrop P. Rockefeller Cancer Institute

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Cohort A: Loncastuximab Tesirine + Rituximab (Lonca-R)	Unfit participants (per simplified geriatric assessment [sGA]) received Lonca-R for 3 cycles (each treatment cycle was 3 weeks). A response-adapted approach was implemented, where participants achieving complete response (CR) after 3 cycles received 1 additional cycle (4 cycles total), and those with partial response (PR) after 3 cycles received additional cycles based on their cohort assignment (6 cycles total). Loncastuximab tesirine was administered as an intravenous (IV) infusion on Day 2 of Cycle 1 and Day 1 (prior to rituximab administration) of subsequent cycles. Participants received 150 μg/kg loncastuximab tesirine for 2 cycles, followed by 75 μg/kg loncastuximab tesirine for subsequent cycles. Rituximab was administered as an IV infusion on Day 1 of each cycle at a dose of 375 mg/m^2.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 8, 2022	Dec 20, 2024

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

All-Treated Population: all participants who received at least 1 dose of study drug.

Arm/Group Information

ID	Title	Description
BG000	Cohort A: Loncastuximab Tesirine + Rituximab (Lonca-R)	Unfit participants (per sGA) received Lonca-R for 3 cycles (each treatment cycle was 3 weeks). A response-adapted approach was implemented, where participants achieving CR after 3 cycles received 1 additional cycle (4 cycles total), and those with PR after 3 cycles received additional cycles based on their cohort assignment (6 cycles total). Loncastuximab tesirine was administered as an IV infusion on Day 2 of Cycle 1 and Day 1 (prior to rituximab administration) of subsequent cycles. Participants received 150 μg/kg loncastuximab tesirine for 2 cycles, followed by 75 μg/kg loncastuximab tesirine for subsequent cycles. Rituximab was administered as an IV infusion on Day 1 of each cycle at a dose of 375 mg/m^2.
BG001	Cohort B: Loncastuximab Tesirine + Rituximab (Lonca-R)	Frail participants (per sGA) or participants with cardiac comorbidities received Lonca-R for 3 cycles (each treatment cycle was 3 weeks). A response-adapted approach was implemented, where participants achieving CR after 3 cycles received 1 additional cycle (4 cycles total), and those with PR or SD (Cohort B only) after 3 cycles received additional cycles based on their cohort assignment (6 cycles total). Loncastuximab tesirine was administered as an IV infusion on Day 2 of Cycle 1 and Day 1 (prior to rituximab administration) of subsequent cycles. Participants received 150 μg/kg loncastuximab tesirine for 2 cycles, followed by 75 μg/kg loncastuximab tesirine for subsequent cycles. Rituximab was administered as an IV infusion on Day 1 of each cycle at a dose of 375 mg/m^2.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00084.1± 3.48 BG00180.0± 7.07 BG00281.7± 6.16

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0003 BG0019 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0002 BG0011 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

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

CR Rate

Defined as percentage of participants with a best overall response (BOR) of CR as determined by the Investigator according to the 2014 Lugano Classification criteria.

CR was defined as achieving:

Complete metabolic response for positron emission tomography (PET)-computed tomography (CT) OR
Complete radiologic response (target node regress to <1.5 cm, no non-measured lesions, no organ enlargement, no new lesions and normal bone marrow morphology) for CT if disease was not fluorodeoxyglucose (FDG)-avid at baseline.

All-Treated Population: All participants who received at least 1 dose of study drug.

Posted

Number

95% Confidence Interval

percentage of participants

Up to a maximum of 17.1 months

ID	Title	Description
OG000	Cohort A: Loncastuximab Tesirine + Rituximab (Lonca-R)	Unfit participants (per sGA) received Lonca-R for 3 cycles (each treatment cycle was 3 weeks). A response-adapted approach was implemented, where participants achieving CR after 3 cycles received 1 additional cycle (4 cycles total), and those with PR after 3 cycles received additional cycles based on their cohort assignment (6 cycles total). Loncastuximab tesirine was administered as an IV infusion on Day 2 of Cycle 1 and Day 1 (prior to rituximab administration) of subsequent cycles. Participants received 150 μg/kg loncastuximab tesirine for 2 cycles, followed by 75 μg/kg loncastuximab tesirine for subsequent cycles. Rituximab was administered as an IV infusion on Day 1 of each cycle at a dose of 375 mg/m^2.
OG001	Cohort B: Loncastuximab Tesirine + Rituximab (Lonca-R)	Frail participants (per sGA) or participants with cardiac comorbidities received Lonca-R for 3 cycles (each treatment cycle was 3 weeks). A response-adapted approach was implemented, where participants achieving CR after 3 cycles received 1 additional cycle (4 cycles total), and those with PR or SD (Cohort B only) after 3 cycles received additional cycles based on their cohort assignment (6 cycles total). Loncastuximab tesirine was administered as an IV infusion on Day 2 of Cycle 1 and Day 1 (prior to rituximab administration) of subsequent cycles. Participants received 150 μg/kg loncastuximab tesirine for 2 cycles, followed by 75 μg/kg loncastuximab tesirine for subsequent cycles. Rituximab was administered as an IV infusion on Day 1 of each cycle at a dose of 375 mg/m^2.

Units	Counts
Participants	OG00017 OG00124

Title

Denominators

Categories

Title	Measurements
	OG00052.9(27.8 to 77.0) OG00141.7(22.1 to 63.4)

Primary

Cohort B: Percentage of Participants Who Completed 4 Cycles of Treatment

Defined by the number of participants who completed a total of 4 cycles of therapy divided by the total number of participants * 100.

All-Treated Population: All participants who received at least 1 dose of study drug.

Posted

Number

percentage of participants

Up to 12 weeks (3 week cycle length)

ID	Title	Description
OG000	Cohort B: Loncastuximab Tesirine + Rituximab (Lonca-R)	Frail participants (per sGA) or participants with cardiac comorbidities received Lonca-R for 3 cycles (each treatment cycle was 3 weeks). A response-adapted approach was implemented, where participants achieving CR after 3 cycles received 1 additional cycle (4 cycles total), and those with PR or SD (Cohort B only) after 3 cycles received additional cycles based on their cohort assignment (6 cycles total). Loncastuximab tesirine was administered as an IV infusion on Day 2 of Cycle 1 and Day 1 (prior to rituximab administration) of subsequent cycles. Participants received 150 μg/kg loncastuximab tesirine for 2 cycles, followed by 75 μg/kg loncastuximab tesirine for subsequent cycles. Rituximab was administered as an IV infusion on Day 1 of each cycle at a dose of 375 mg/m^2.

Units	Counts
Participants

Secondary

Overall Response Rate (ORR)

Defined as the percentage of participants who achieved either CR or PR as BOR as determined by Investigator according to the 2014 Lugano Classification criteria.

CR was defined as achieving:

Complete metabolic response for PET-CT OR
Complete radiologic response (target node regress to <1.5 cm, no non-measured lesions, no organ enlargement, no new lesions and normal bone marrow morphology) for CT if disease was not FDG-avid at baseline.

PR was defined as achieving:

Partial metabolic response (findings indicate residual disease) for PET-CT OR
Partial remission (>50% decrease in target measurable nodes, regression/ absence/ no increase of non-measured lesions, spleen regressed by >50% in length and no new lesions) for CT if disease was not FDG-avid at baseline.

All-Treated Population: All participants who received at least 1 dose of study drug.

Posted

Number

95% Confidence Interval

percentage of participants

Up to a maximum of 17.1 months

ID	Title	Description
OG000	Cohort A: Loncastuximab Tesirine + Rituximab (Lonca-R)	Unfit participants (per sGA) received Lonca-R for 3 cycles (each treatment cycle was 3 weeks). A response-adapted approach was implemented, where participants achieving CR after 3 cycles received 1 additional cycle (4 cycles total), and those with PR after 3 cycles received additional cycles based on their cohort assignment (6 cycles total). Loncastuximab tesirine was administered as an IV infusion on Day 2 of Cycle 1 and Day 1 (prior to rituximab administration) of subsequent cycles. Participants received 150 μg/kg loncastuximab tesirine for 2 cycles, followed by 75 μg/kg loncastuximab tesirine for subsequent cycles. Rituximab was administered as an IV infusion on Day 1 of each cycle at a dose of 375 mg/m^2.

Secondary

2-year Progression-free Survival (PFS)

PFS was defined as the time from first dose of study drug until the first date of either disease progression (PD) or death due to any cause. The 2-year PFS was defined as the percentage of participants that were PFS event-free at 2 years per investigator assessment with 95% confidence interval (CI) estimated using Kaplan-Meier method.

All-Treated Population: All participants who received at least 1 dose of study drug. No data was collected for this endpoint due to study early termination.

Posted

2 years

ID	Title	Description
OG000	Cohort A: Loncastuximab Tesirine + Rituximab (Lonca-R)	Unfit participants (per sGA) received Lonca-R for 3 cycles (each treatment cycle was 3 weeks). A response-adapted approach was implemented, where participants achieving CR after 3 cycles received 1 additional cycle (4 cycles total), and those with PR after 3 cycles received additional cycles based on their cohort assignment (6 cycles total). Loncastuximab tesirine was administered as an IV infusion on Day 2 of Cycle 1 and Day 1 (prior to rituximab administration) of subsequent cycles. Participants received 150 μg/kg loncastuximab tesirine for 2 cycles, followed by 75 μg/kg loncastuximab tesirine for subsequent cycles. Rituximab was administered as an IV infusion on Day 1 of each cycle at a dose of 375 mg/m^2.
OG001	Cohort B: Loncastuximab Tesirine + Rituximab (Lonca-R)	Frail participants (per sGA) or participants with cardiac comorbidities received Lonca-R for 3 cycles (each treatment cycle was 3 weeks). A response-adapted approach was implemented, where participants achieving CR after 3 cycles received 1 additional cycle (4 cycles total), and those with PR or SD (Cohort B only) after 3 cycles received additional cycles based on their cohort assignment (6 cycles total). Loncastuximab tesirine was administered as an IV infusion on Day 2 of Cycle 1 and Day 1 (prior to rituximab administration) of subsequent cycles. Participants received 150 μg/kg loncastuximab tesirine for 2 cycles, followed by 75 μg/kg loncastuximab tesirine for subsequent cycles. Rituximab was administered as an IV infusion on Day 1 of each cycle at a dose of 375 mg/m^2.

Secondary

3-year Overall Survival (OS)

OS was defined as the time from randomization date until death due to any cause. The 3-year OS was defined as the percentage of participants that were OS event-free at 3 years with 95% CI estimated using Kaplan-Meier method.

All-Treated Population: All participants who received at least 1 dose of study drug. No data was collected for this endpoint due to study early termination.

Posted

3 years

ID	Title	Description
OG000	Cohort A: Loncastuximab Tesirine + Rituximab (Lonca-R)	Unfit participants (per sGA) received Lonca-R for 3 cycles (each treatment cycle was 3 weeks). A response-adapted approach was implemented, where participants achieving CR after 3 cycles received 1 additional cycle (4 cycles total), and those with PR after 3 cycles received additional cycles based on their cohort assignment (6 cycles total). Loncastuximab tesirine was administered as an IV infusion on Day 2 of Cycle 1 and Day 1 (prior to rituximab administration) of subsequent cycles. Participants received 150 μg/kg loncastuximab tesirine for 2 cycles, followed by 75 μg/kg loncastuximab tesirine for subsequent cycles. Rituximab was administered as an IV infusion on Day 1 of each cycle at a dose of 375 mg/m^2.
OG001	Cohort B: Loncastuximab Tesirine + Rituximab (Lonca-R)	Frail participants (per sGA) or participants with cardiac comorbidities received Lonca-R for 3 cycles (each treatment cycle was 3 weeks). A response-adapted approach was implemented, where participants achieving CR after 3 cycles received 1 additional cycle (4 cycles total), and those with PR or SD (Cohort B only) after 3 cycles received additional cycles based on their cohort assignment (6 cycles total). Loncastuximab tesirine was administered as an IV infusion on Day 2 of Cycle 1 and Day 1 (prior to rituximab administration) of subsequent cycles. Participants received 150 μg/kg loncastuximab tesirine for 2 cycles, followed by 75 μg/kg loncastuximab tesirine for subsequent cycles. Rituximab was administered as an IV infusion on Day 1 of each cycle at a dose of 375 mg/m^2.

Secondary

Duration of Response (DoR)

Defined for participants with CR or PR only as the interval between the date of initial documentation of a response and the date of the first documented progressive disease (based on radiographic or clinical progression at end of study or death due to any cause, whichever occurred first) per investigator assessment with 95% CI estimated using Kaplan-Meier method.

CR was defined as achieving:

Complete metabolic response for PET-CT OR
Complete radiologic response (target node regress to <1.5 cm, no non-measured lesions, no organ enlargement, no new lesions and normal bone marrow morphology) for CT if disease was not FDG-avid at baseline.

PR was defined as achieving:

Partial metabolic response (findings indicate residual disease) for PET-CT OR
Partial remission (>50% decrease in target measurable nodes, regression/ absence/ no increase of non-measured lesions, spleen regressed by >50% in length and no new lesions) for CT if disease was not FDG-avid at baseline.

All-Treated Population: All participants who received at least 1 dose of study drug. Inclusive of participants who were censored.

Posted

Median

95% Confidence Interval

months

Up to a maximum of 17.1 months

ID	Title	Description
OG000	Cohort A: Loncastuximab Tesirine + Rituximab (Lonca-R)	Unfit participants (per sGA) received Lonca-R for 3 cycles (each treatment cycle was 3 weeks). A response-adapted approach was implemented, where participants achieving CR after 3 cycles received 1 additional cycle (4 cycles total), and those with PR after 3 cycles received additional cycles based on their cohort assignment (6 cycles total). Loncastuximab tesirine was administered as an IV infusion on Day 2 of Cycle 1 and Day 1 (prior to rituximab administration) of subsequent cycles. Participants received 150 μg/kg loncastuximab tesirine for 2 cycles, followed by 75 μg/kg loncastuximab tesirine for subsequent cycles. Rituximab was administered as an IV infusion on Day 1 of each cycle at a dose of 375 mg/m^2.

Secondary

Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)

An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product. A TEAE was defined as an AE that occurred or worsened in the period extending from the first dose of study drug to 15 weeks after the last dose of study drugs in this study or start of a new anticancer therapy, whichever was earlier. A serious AE (SAE) was defined as an AE that resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or an important medical event. A severe AE was defined as Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grade 3 (severe) or above.

Clinically significant changes in safety laboratory variables, vital signs, physical examinations, and Eastern Cooperative Oncology Group performance score were recorded as AEs.

All-Treated Population: All participants who received at least 1 dose of study drug.

Posted

Count of Participants

Participants

Up to approximately 8 months

ID	Title	Description
OG000	Cohort A: Loncastuximab Tesirine + Rituximab (Lonca-R)	Unfit participants (per sGA) received Lonca-R for 3 cycles (each treatment cycle was 3 weeks). A response-adapted approach was implemented, where participants achieving CR after 3 cycles received 1 additional cycle (4 cycles total), and those with PR after 3 cycles received additional cycles based on their cohort assignment (6 cycles total). Loncastuximab tesirine was administered as an IV infusion on Day 2 of Cycle 1 and Day 1 (prior to rituximab administration) of subsequent cycles. Participants received 150 μg/kg loncastuximab tesirine for 2 cycles, followed by 75 μg/kg loncastuximab tesirine for subsequent cycles. Rituximab was administered as an IV infusion on Day 1 of each cycle at a dose of 375 mg/m^2.

Secondary

Maximum Observed Concentration (Cmax) of Conjugated Antibody

Pharmacokinetic (PK) was assessed by a central laboratory using validated bioanalytical methods. Analysis considered model development for conjugated antibodies and total antibodies only, as pre-specified in protocol section 9.9.

PK Population: All participants who received study drug and have at least 1 pre-(Cycle 1 Day 1) and 1 post-dose valid PK assessment. Inclusive of only participants with available data at each timepoint.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Cycle 1 Day 2: predose (preferably within 2 h prior to start of infusion) and at the end (within -5 to +10 min) of loncastuximab tesirine infusion; Cycles 2-6 Day 1 predose and at the end of loncastuximab tesirine infusion (3 week cycle length)

ID	Title	Description
OG000	Cohort A: Loncastuximab Tesirine + Rituximab (Lonca-R)	Unfit participants (per sGA) received Lonca-R for 3 cycles (each treatment cycle was 3 weeks). A response-adapted approach was implemented, where participants achieving CR after 3 cycles received 1 additional cycle (4 cycles total), and those with PR after 3 cycles received additional cycles based on their cohort assignment (6 cycles total). Loncastuximab tesirine was administered as an IV infusion on Day 2 of Cycle 1 and Day 1 (prior to rituximab administration) of subsequent cycles. Participants received 150 μg/kg loncastuximab tesirine for 2 cycles, followed by 75 μg/kg loncastuximab tesirine for subsequent cycles. Rituximab was administered as an IV infusion on Day 1 of each cycle at a dose of 375 mg/m^2.
OG001

Secondary

Cmax of Total Antibody

PK was assessed by a central laboratory using validated bioanalytical methods. Analysis considered model development for conjugated antibodies and total antibodies only, as pre-specified in protocol section 9.9.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

ID	Title	Description
OG000	Cohort A: Loncastuximab Tesirine + Rituximab (Lonca-R)	Unfit participants (per sGA) received Lonca-R for 3 cycles (each treatment cycle was 3 weeks). A response-adapted approach was implemented, where participants achieving CR after 3 cycles received 1 additional cycle (4 cycles total), and those with PR after 3 cycles received additional cycles based on their cohort assignment (6 cycles total). Loncastuximab tesirine was administered as an IV infusion on Day 2 of Cycle 1 and Day 1 (prior to rituximab administration) of subsequent cycles. Participants received 150 μg/kg loncastuximab tesirine for 2 cycles, followed by 75 μg/kg loncastuximab tesirine for subsequent cycles. Rituximab was administered as an IV infusion on Day 1 of each cycle at a dose of 375 mg/m^2.
OG001	Cohort B: Loncastuximab Tesirine + Rituximab (Lonca-R)

Secondary

Trough Concentration (Ctrough) of Conjugated Antibody

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Cycle 1 Day 2: predose (preferably within 2 h prior to start of infusion); Cycles 2-6 Day 1 predose (3 week cycle length)

ID	Title	Description
OG000	Cohort A: Loncastuximab Tesirine + Rituximab (Lonca-R)	Unfit participants (per sGA) received Lonca-R for 3 cycles (each treatment cycle was 3 weeks). A response-adapted approach was implemented, where participants achieving CR after 3 cycles received 1 additional cycle (4 cycles total), and those with PR after 3 cycles received additional cycles based on their cohort assignment (6 cycles total). Loncastuximab tesirine was administered as an IV infusion on Day 2 of Cycle 1 and Day 1 (prior to rituximab administration) of subsequent cycles. Participants received 150 μg/kg loncastuximab tesirine for 2 cycles, followed by 75 μg/kg loncastuximab tesirine for subsequent cycles. Rituximab was administered as an IV infusion on Day 1 of each cycle at a dose of 375 mg/m^2.
OG001	Cohort B: Loncastuximab Tesirine + Rituximab (Lonca-R)

Secondary

Ctrough of Total Antibody

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Cycle 1 Day 2: predose (preferably within 2 h prior to start of infusion); Cycles 2-6 Day 1 predose (3 week cycle length)

ID	Title	Description
OG000	Cohort A: Loncastuximab Tesirine + Rituximab (Lonca-R)	Unfit participants (per sGA) received Lonca-R for 3 cycles (each treatment cycle was 3 weeks). A response-adapted approach was implemented, where participants achieving CR after 3 cycles received 1 additional cycle (4 cycles total), and those with PR after 3 cycles received additional cycles based on their cohort assignment (6 cycles total). Loncastuximab tesirine was administered as an IV infusion on Day 2 of Cycle 1 and Day 1 (prior to rituximab administration) of subsequent cycles. Participants received 150 μg/kg loncastuximab tesirine for 2 cycles, followed by 75 μg/kg loncastuximab tesirine for subsequent cycles. Rituximab was administered as an IV infusion on Day 1 of each cycle at a dose of 375 mg/m^2.
OG001	Cohort B: Loncastuximab Tesirine + Rituximab (Lonca-R)

Secondary

Number of Participants With Confirmed Positive Anti-Drug Antibody (ADA) Response

Detection of ADAs against loncastuximab tesirine was performed by using a screening assay for identification of antibody positive samples/participants and a confirmation assay. A participant was considered to have an ADA response if ADA sample was positive at any pre-specified, post-treatment timepoint.

Immunogenicity Population: All participants who received study drug and had at least 1 valid anti-drug antibody assessment.

Posted

Count of Participants

Participants

Cycle 1 Day 2 pre-dose (preferably within 2 h prior to start of infusion) then Day 1 pre-dose of Cycles 2, 4, and 6 (3 week cycle length)

ID	Title	Description
OG000	Cohort A: Loncastuximab Tesirine + Rituximab (Lonca-R)	Unfit participants (per sGA) received Lonca-R for 3 cycles (each treatment cycle was 3 weeks). A response-adapted approach was implemented, where participants achieving CR after 3 cycles received 1 additional cycle (4 cycles total), and those with PR after 3 cycles received additional cycles based on their cohort assignment (6 cycles total). Loncastuximab tesirine was administered as an IV infusion on Day 2 of Cycle 1 and Day 1 (prior to rituximab administration) of subsequent cycles. Participants received 150 μg/kg loncastuximab tesirine for 2 cycles, followed by 75 μg/kg loncastuximab tesirine for subsequent cycles. Rituximab was administered as an IV infusion on Day 1 of each cycle at a dose of 375 mg/m^2.
OG001	Cohort B: Loncastuximab Tesirine + Rituximab (Lonca-R)

Secondary

Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Subscale and Composite Scores

The following score ranges were possible for the FACT-Lym subscale and composite scores, with higher scores indicating better quality of life/outcome: 0 to 28 for physical well-being, social/family well-being, and functional well-being; 0 to 24 for emotional well-being; 0 to 60 for lymphoma subscale score; 0 to 116 for FACT-Lym trial outcome index; 0 to 108 for FACT-G total score; and 0 to 168 for FACT-Lym Total. An increase in subscale/composite scores from Baseline indicated better quality of life/outcome.

Patient-reported Outcomes Population: All participants who received at least one dose of study treatment and completed at least one questionnaire at Baseline and at one post Baseline visit.

Posted

Mean

Standard Deviation

score on a scale

Baseline and End of Treatment Visit (a maximum of 19 weeks)

ID	Title	Description
OG000	Cohort A: Loncastuximab Tesirine + Rituximab (Lonca-R)	Unfit participants (per sGA) received Lonca-R for 3 cycles (each treatment cycle was 3 weeks). A response-adapted approach was implemented, where participants achieving CR after 3 cycles received 1 additional cycle (4 cycles total), and those with PR after 3 cycles received additional cycles based on their cohort assignment (6 cycles total). Loncastuximab tesirine was administered as an IV infusion on Day 2 of Cycle 1 and Day 1 (prior to rituximab administration) of subsequent cycles. Participants received 150 μg/kg loncastuximab tesirine for 2 cycles, followed by 75 μg/kg loncastuximab tesirine for subsequent cycles. Rituximab was administered as an IV infusion on Day 1 of each cycle at a dose of 375 mg/m^2.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cohort A: Loncastuximab Tesirine + Rituximab (Lonca-R)	Unfit participants (per sGA) received Lonca-R for 3 cycles (each treatment cycle was 3 weeks). A response-adapted approach was implemented, where participants achieving CR after 3 cycles received 1 additional cycle (4 cycles total), and those with PR after 3 cycles received additional cycles based on their cohort assignment (6 cycles total). Loncastuximab tesirine was administered as an IV infusion on Day 2 of Cycle 1 and Day 1 (prior to rituximab administration) of subsequent cycles. Participants received 150 μg/kg loncastuximab tesirine for 2 cycles, followed by 75 μg/kg loncastuximab tesirine for subsequent cycles. Rituximab was administered as an IV infusion on Day 1 of each cycle at a dose of 375 mg/m^2.	5	17	13	17	17	17
EG001	Cohort B: Loncastuximab Tesirine + Rituximab (Lonca-R)	Frail participants (per sGA) or participants with cardiac comorbidities received Lonca-R for 3 cycles (each treatment cycle was 3 weeks). A response-adapted approach was implemented, where participants achieving CR after 3 cycles received 1 additional cycle (4 cycles total), and those with PR or SD (Cohort B only) after 3 cycles received additional cycles based on their cohort assignment (6 cycles total). Loncastuximab tesirine was administered as an IV infusion on Day 2 of Cycle 1 and Day 1 (prior to rituximab administration) of subsequent cycles. Participants received 150 μg/kg loncastuximab tesirine for 2 cycles, followed by 75 μg/kg loncastuximab tesirine for subsequent cycles. Rituximab was administered as an IV infusion on Day 1 of each cycle at a dose of 375 mg/m^2.	10	24	16	24	22	24

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (24.1)	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected24 at risk
Pericardial effusion	Cardiac disorders	MedDRA (24.1)	Systematic Assessment	EG0002 events2 affected17 at risk EG0011 events1 affected24 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0011 events1 affected24 at risk
Cardiac failure	Cardiac disorders	MedDRA (24.1)	Systematic Assessment	EG0002 events2 affected17 at risk EG0010 events0 affected24 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0011 events1 affected24 at risk
Cardiogenic shock	Cardiac disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Ascites	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected24 at risk
Dysphagia	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected24 at risk
Vomiting	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Death	General disorders	MedDRA (24.1)	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected24 at risk
Oedema peripheral	General disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Pneumonia	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0015 events5 affected24 at risk
Sepsis	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0003 events2 affected17 at risk EG0012 events2 affected24 at risk
COVID-19	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
COVID-19 pneumonia	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected24 at risk
Influenza	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Septic shock	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected24 at risk
Parkinson's disease	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected24 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA (24.1)	Systematic Assessment	EG0000 events0 affected17 at risk EG0012 events2 affected24 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA (24.1)	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected24 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG0005 events5 affected17 at risk EG0012 events2 affected24 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG0002 events2 affected17 at risk EG0012 events2 affected24 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0011 events1 affected24 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0011 events1 affected24 at risk
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected24 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG0000 events0 affected17 at risk EG0013 events1 affected24 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Pulmonary fibrosis	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected24 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected24 at risk
Embolism	Vascular disorders	MedDRA (24.1)	Systematic Assessment	EG0000 events0 affected17 at risk EG0012 events2 affected24 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (24.1)	Systematic Assessment	EG0002 events2 affected17 at risk EG0014 events3 affected24 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA (24.1)	Systematic Assessment	EG0002 events2 affected17 at risk EG0013 events2 affected24 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (24.1)	Systematic Assessment	EG0003 events3 affected17 at risk EG0011 events1 affected24 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (24.1)	Systematic Assessment	EG0002 events2 affected17 at risk EG0011 events1 affected24 at risk
Pericardial effusion	Cardiac disorders	MedDRA (24.1)	Systematic Assessment	EG0006 events5 affected17 at risk EG0012 events2 affected24 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0013 events3 affected24 at risk
Angina pectoris	Cardiac disorders	MedDRA (24.1)	Systematic Assessment	EG0002 events2 affected17 at risk EG0010 events0 affected24 at risk
Bradycardia	Cardiac disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0011 events1 affected24 at risk
Atrial tachycardia	Cardiac disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Cardiac failure	Cardiac disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Cardiac failure acute	Cardiac disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Sinus tachycardia	Cardiac disorders	MedDRA (24.1)	Systematic Assessment	EG0002 events1 affected17 at risk EG0010 events0 affected24 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Tachycardia	Cardiac disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Periorbital oedema	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Constipation	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0002 events2 affected17 at risk EG0014 events4 affected24 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0003 events2 affected17 at risk EG0014 events4 affected24 at risk
Nausea	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0004 events3 affected17 at risk EG0011 events1 affected24 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0011 events1 affected24 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Gastric ulcer	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Fatigue	General disorders	MedDRA (24.1)	Systematic Assessment	EG0009 events9 affected17 at risk EG00110 events10 affected24 at risk
Oedema peripheral	General disorders	MedDRA (24.1)	Systematic Assessment	EG00011 events8 affected17 at risk EG0017 events7 affected24 at risk
Face oedema	General disorders	MedDRA (24.1)	Systematic Assessment	EG0003 events3 affected17 at risk EG0010 events0 affected24 at risk
Chest discomfort	General disorders	MedDRA (24.1)	Systematic Assessment	EG0000 events0 affected17 at risk EG0012 events2 affected24 at risk
Generalised oedema	General disorders	MedDRA (24.1)	Systematic Assessment	EG0002 events2 affected17 at risk EG0010 events0 affected24 at risk
Influenza like illness	General disorders	MedDRA (24.1)	Systematic Assessment	EG0002 events2 affected17 at risk EG0010 events0 affected24 at risk
Peripheral swelling	General disorders	MedDRA (24.1)	Systematic Assessment	EG0003 events2 affected17 at risk EG0010 events0 affected24 at risk
Catheter site erythema	General disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Chills	General disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Mucosal inflammation	General disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Pain	General disorders	MedDRA (24.1)	Systematic Assessment	EG0003 events1 affected17 at risk EG0010 events0 affected24 at risk
Pyrexia	General disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Swelling face	General disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Hypogammaglobulinaemia	Immune system disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
COVID-19	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0003 events3 affected17 at risk EG0011 events1 affected24 at risk
Influenza	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0002 events2 affected17 at risk EG0011 events1 affected24 at risk
Pneumonia	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0002 events1 affected17 at risk EG0012 events2 affected24 at risk
Urinary tract infection	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0013 events2 affected24 at risk
Cytomegalovirus gastritis	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Enterocolitis infectious	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Folliculitis	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Herpes zoster	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Oesophageal infection	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Viral infection	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0011 events1 affected24 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Skin abrasion	Injury, poisoning and procedural complications	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA (24.1)	Systematic Assessment	EG0004 events3 affected17 at risk EG0012 events2 affected24 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA (24.1)	Systematic Assessment	EG0003 events3 affected17 at risk EG0011 events1 affected24 at risk
Blood creatinine increased	Investigations	MedDRA (24.1)	Systematic Assessment	EG0002 events2 affected17 at risk EG0011 events1 affected24 at risk
Weight decreased	Investigations	MedDRA (24.1)	Systematic Assessment	EG0000 events0 affected17 at risk EG0013 events3 affected24 at risk
Weight increased	Investigations	MedDRA (24.1)	Systematic Assessment	EG0002 events2 affected17 at risk EG0011 events1 affected24 at risk
Alanine aminotransferase increased	Investigations	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0011 events1 affected24 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0011 events1 affected24 at risk
Lipase increased	Investigations	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0011 events1 affected24 at risk
Amylase increased	Investigations	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Blood pressure increased	Investigations	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Glomerular filtration rate decreased	Investigations	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (24.1)	Systematic Assessment	EG0004 events4 affected17 at risk EG0016 events6 affected24 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (24.1)	Systematic Assessment	EG0006 events3 affected17 at risk EG0015 events3 affected24 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA (24.1)	Systematic Assessment	EG0003 events3 affected17 at risk EG0014 events3 affected24 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA (24.1)	Systematic Assessment	EG0005 events3 affected17 at risk EG0013 events2 affected24 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (24.1)	Systematic Assessment	EG0002 events2 affected17 at risk EG0011 events1 affected24 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA (24.1)	Systematic Assessment	EG0002 events2 affected17 at risk EG0010 events0 affected24 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA (24.1)	Systematic Assessment	EG0004 events2 affected17 at risk EG0010 events0 affected24 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0011 events1 affected24 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0013 events3 affected24 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0012 events2 affected24 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0002 events2 affected17 at risk EG0010 events0 affected24 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Dizziness	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG0004 events4 affected17 at risk EG0010 events0 affected24 at risk
Dysgeusia	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG0002 events2 affected17 at risk EG0011 events1 affected24 at risk
Headache	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Memory impairment	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Neuralgia	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Thrombosis in device	Product Issues	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Insomnia	Psychiatric disorders	MedDRA (24.1)	Systematic Assessment	EG0004 events4 affected17 at risk EG0011 events1 affected24 at risk
Confusional state	Psychiatric disorders	MedDRA (24.1)	Systematic Assessment	EG0002 events2 affected17 at risk EG0011 events1 affected24 at risk
Anxiety	Psychiatric disorders	MedDRA (24.1)	Systematic Assessment	EG0000 events0 affected17 at risk EG0012 events2 affected24 at risk
Agitation	Psychiatric disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Delirium	Psychiatric disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Haematuria	Renal and urinary disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Vaginal discharge	Reproductive system and breast disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG0009 events9 affected17 at risk EG0017 events5 affected24 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG0009 events8 affected17 at risk EG0016 events5 affected24 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG0006 events6 affected17 at risk EG0012 events2 affected24 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0013 events3 affected24 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0011 events1 affected24 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0011 events1 affected24 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Bronchiectasis	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG0002 events1 affected17 at risk EG0010 events0 affected24 at risk
Photosensitivity reaction	Skin and subcutaneous tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0003 events3 affected17 at risk EG0014 events4 affected24 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0004 events4 affected17 at risk EG0013 events3 affected24 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0002 events2 affected17 at risk EG0012 events2 affected24 at risk
Dermatitis bullous	Skin and subcutaneous tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0002 events2 affected17 at risk EG0011 events1 affected24 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0002 events1 affected17 at risk EG0012 events2 affected24 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0012 events2 affected24 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0002 events1 affected17 at risk EG0011 events1 affected24 at risk
Rash macular	Skin and subcutaneous tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0011 events1 affected24 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0011 events1 affected24 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0002 events1 affected17 at risk EG0010 events0 affected24 at risk
Night sweats	Skin and subcutaneous tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Skin weeping	Skin and subcutaneous tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Deep vein thrombosis	Vascular disorders	MedDRA (24.1)	Systematic Assessment	EG0002 events2 affected17 at risk EG0011 events1 affected24 at risk
Hypotension	Vascular disorders	MedDRA (24.1)	Systematic Assessment	EG0003 events3 affected17 at risk EG0010 events0 affected24 at risk
Hypertension	Vascular disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0011 events1 affected24 at risk
Haematoma	Vascular disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk
Superficial vein thrombosis	Vascular disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected24 at risk

Due to the early termination of the study, the objectives of the study could not be fully assessed (e.g. overall survival). The median duration of follow-up for all participants was limited because of early termination of the study.

Certain Agreements

ID	Term
D016403	Lymphoma, Large B-Cell, Diffuse
D008223	Lymphoma
D008228	Lymphoma, Non-Hodgkin

Ancestor Terms

ID	Term
D016393	Lymphoma, B-Cell
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	Term
C000710749	loncastuximab tesirine
D000069283	Rituximab

Ancestor Terms

ID	Term
D058846	Antibodies, Monoclonal, Murine-Derived
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins

Frail participants (per sGA) or participants with cardiac comorbidities received Lonca-R for 3 cycles (each treatment cycle was 3 weeks). A response-adapted approach was implemented, where participants achieving CR after 3 cycles received 1 additional cycle (4 cycles total), and those with PR or SD (Cohort B only) after 3 cycles received additional cycles based on their cohort assignment (6 cycles total).

Loncastuximab tesirine was administered as an IV infusion on Day 2 of Cycle 1 and Day 1 (prior to rituximab administration) of subsequent cycles. Participants received 150 μg/kg loncastuximab tesirine for 2 cycles, followed by 75 μg/kg loncastuximab tesirine for subsequent cycles. Rituximab was administered as an IV infusion on Day 1 of each cycle at a dose of 375 mg/m^2.