Trial Outcomes & Findings for A Study of Loncastuximab Tesirine and Rituximab (Lonca-R) in Previously Untreated Unfit/Frail Participants With Diffuse Large B-cell Lymphoma (DLBCL) (NCT NCT05144009)

Last Updated: 2025-01-30

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

41 participants

Primary outcome timeframe

Up to a maximum of 17.1 months

Results posted on

2025-01-30

Participant Flow

A total of 41 participants were enrolled in the Unites States and Spain between June 2022 and January 2024.

Participant milestones

Participant milestones
Measure	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.	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 stable disease (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.
Overall Study STARTED	17	24
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	17	24

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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 stable disease (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.
Overall Study Lost to Follow-up	0	1
Overall Study Study Termination by the Sponsor	11	11
Overall Study Disease Progression	1	0
Overall Study Participant Decision	0	2
Overall Study Death	5	10

Baseline Characteristics

A Study of Loncastuximab Tesirine and Rituximab (Lonca-R) in Previously Untreated Unfit/Frail Participants With Diffuse Large B-cell Lymphoma (DLBCL)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort A: Loncastuximab Tesirine + Rituximab (Lonca-R) n=17 Participants 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.	Cohort B: Loncastuximab Tesirine + Rituximab (Lonca-R) n=24 Participants 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.	Total n=41 Participants Total of all reporting groups
Age, Continuous	84.1 years STANDARD_DEVIATION 3.48 • n=99 Participants	80.0 years STANDARD_DEVIATION 7.07 • n=107 Participants	81.7 years STANDARD_DEVIATION 6.16 • n=206 Participants
Sex: Female, Male Female	3 Participants n=99 Participants	9 Participants n=107 Participants	12 Participants n=206 Participants
Sex: Female, Male Male	14 Participants n=99 Participants	15 Participants n=107 Participants	29 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=99 Participants	1 Participants n=107 Participants	3 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	14 Participants n=99 Participants	20 Participants n=107 Participants	34 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=99 Participants	3 Participants n=107 Participants	4 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	2 Participants n=107 Participants	2 Participants n=206 Participants
Race (NIH/OMB) White	16 Participants n=99 Participants	22 Participants n=107 Participants	38 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants

PRIMARY outcome

Timeframe: Up to a maximum of 17.1 months

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

Outcome measures

Outcome measures
Measure	Cohort A: Loncastuximab Tesirine + Rituximab (Lonca-R) n=17 Participants 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.	Cohort B: Loncastuximab Tesirine + Rituximab (Lonca-R) n=24 Participants 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.
CR Rate	52.9 percentage of participants Interval 27.8 to 77.0	41.7 percentage of participants Interval 22.1 to 63.4

PRIMARY outcome

Timeframe: Up to 12 weeks (3 week cycle length)

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

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

Outcome measures

Outcome measures
Measure	Cohort A: Loncastuximab Tesirine + Rituximab (Lonca-R) n=24 Participants 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.	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.
Cohort B: Percentage of Participants Who Completed 4 Cycles of Treatment	33.3 percentage of participants	—

SECONDARY outcome

Timeframe: Up to a maximum of 17.1 months

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

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.

Outcome measures

Outcome measures
Measure	Cohort A: Loncastuximab Tesirine + Rituximab (Lonca-R) n=17 Participants 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.	Cohort B: Loncastuximab Tesirine + Rituximab (Lonca-R) n=24 Participants 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.
Overall Response Rate (ORR)	94.1 percentage of participants Interval 71.3 to 99.9	66.7 percentage of participants Interval 44.7 to 84.4

SECONDARY outcome

Timeframe: 2 years

Population: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 3 years

Population: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to a maximum of 17.1 months

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

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.

Outcome measures

Outcome measures
Measure	Cohort A: Loncastuximab Tesirine + Rituximab (Lonca-R) n=17 Participants 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.	Cohort B: Loncastuximab Tesirine + Rituximab (Lonca-R) n=24 Participants 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.
Duration of Response (DoR)	5.49 months Interval 2.27 to Upper confidence interval was not calculable due to insufficient event data occurring above the median.	NA months Median and confidence intervals were not calculable due to insufficient event data occurring near the median.

SECONDARY outcome

Timeframe: Up to approximately 8 months

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

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.

Outcome measures

Outcome measures
Measure	Cohort A: Loncastuximab Tesirine + Rituximab (Lonca-R) n=17 Participants 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.	Cohort B: Loncastuximab Tesirine + Rituximab (Lonca-R) n=24 Participants 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.
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) Any TEAEs	17 Participants	23 Participants
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) Any CTCAE Grade 3 or Higher TEAEs	13 Participants	18 Participants
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) Any Serious TEAEs	13 Participants	16 Participants

SECONDARY outcome

Timeframe: 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)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Cohort A: Loncastuximab Tesirine + Rituximab (Lonca-R) n=17 Participants 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.	Cohort B: Loncastuximab Tesirine + Rituximab (Lonca-R) n=18 Participants 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.
Maximum Observed Concentration (Cmax) of Conjugated Antibody Cycle 3	1456 ng/mL Geometric Coefficient of Variation 40.6	1407 ng/mL Geometric Coefficient of Variation 29.6
Maximum Observed Concentration (Cmax) of Conjugated Antibody Cycle 4	1581 ng/mL Geometric Coefficient of Variation 28.6	1163 ng/mL Geometric Coefficient of Variation 59.4
Maximum Observed Concentration (Cmax) of Conjugated Antibody Cycle 5	1377 ng/mL Geometric Coefficient of Variation 18.2	1700 ng/mL Geometric Coefficient of Variation 15.2
Maximum Observed Concentration (Cmax) of Conjugated Antibody Cycle 6	1087 ng/mL Geometric Coefficient of Variation 28.2	617 ng/mL Geometric Coefficient of Variation 83.9
Maximum Observed Concentration (Cmax) of Conjugated Antibody Cycle 1	1667 ng/mL Geometric Coefficient of Variation 274	1788 ng/mL Geometric Coefficient of Variation 52.2
Maximum Observed Concentration (Cmax) of Conjugated Antibody Cycle 2	2461 ng/mL Geometric Coefficient of Variation 65.2	2353 ng/mL Geometric Coefficient of Variation 30.5

SECONDARY outcome

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.

Outcome measures

Outcome measures
Measure	Cohort A: Loncastuximab Tesirine + Rituximab (Lonca-R) n=17 Participants 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.	Cohort B: Loncastuximab Tesirine + Rituximab (Lonca-R) n=21 Participants 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.
Cmax of Total Antibody Cycle 6	1466 ng/mL Geometric Coefficient of Variation 19.1	1175 ng/mL Geometric Coefficient of Variation 110
Cmax of Total Antibody Cycle 1	2751 ng/mL Geometric Coefficient of Variation 59.4	1971 ng/mL Geometric Coefficient of Variation 115
Cmax of Total Antibody Cycle 2	3270 ng/mL Geometric Coefficient of Variation 68.6	2746 ng/mL Geometric Coefficient of Variation 33.5
Cmax of Total Antibody Cycle 3	2010 ng/mL Geometric Coefficient of Variation 49.0	1834 ng/mL Geometric Coefficient of Variation 32.6
Cmax of Total Antibody Cycle 4	2044 ng/mL Geometric Coefficient of Variation 44.8	1362 ng/mL Geometric Coefficient of Variation 56.8
Cmax of Total Antibody Cycle 5	1874 ng/mL Geometric Coefficient of Variation 36.0	1799 ng/mL Geometric Coefficient of Variation 25.9

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Cohort A: Loncastuximab Tesirine + Rituximab (Lonca-R) n=15 Participants 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.	Cohort B: Loncastuximab Tesirine + Rituximab (Lonca-R) n=17 Participants 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.
Trough Concentration (Ctrough) of Conjugated Antibody Cycle 2	548 ng/mL Geometric Coefficient of Variation 35.6	449 ng/mL Geometric Coefficient of Variation 70.3
Trough Concentration (Ctrough) of Conjugated Antibody Cycle 3	411 ng/mL Geometric Coefficient of Variation 53.8	479 ng/mL Geometric Coefficient of Variation 35.1
Trough Concentration (Ctrough) of Conjugated Antibody Cycle 4	391 ng/mL Geometric Coefficient of Variation 25.4	436 ng/mL Geometric Coefficient of Variation 32.1
Trough Concentration (Ctrough) of Conjugated Antibody Cycle 5	353 ng/mL Geometric Coefficient of Variation 24.0	453 ng/mL Geometric Coefficient of Variation 34.8
Trough Concentration (Ctrough) of Conjugated Antibody Cycle 1	324 ng/mL Geometric Coefficient of Variation 30.7	215 ng/mL Geometric Coefficient of Variation 142

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Cohort A: Loncastuximab Tesirine + Rituximab (Lonca-R) n=15 Participants 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.	Cohort B: Loncastuximab Tesirine + Rituximab (Lonca-R) n=18 Participants 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.
Ctrough of Total Antibody Cycle 1	503 ng/mL Geometric Coefficient of Variation 75.1	413 ng/mL Geometric Coefficient of Variation 56.9
Ctrough of Total Antibody Cycle 2	805 ng/mL Geometric Coefficient of Variation 68.5	650 ng/mL Geometric Coefficient of Variation 70.2
Ctrough of Total Antibody Cycle 3	619 ng/mL Geometric Coefficient of Variation 75.9	645 ng/mL Geometric Coefficient of Variation 31.5
Ctrough of Total Antibody Cycle 4	633 ng/mL Geometric Coefficient of Variation 69.1	627 ng/mL Geometric Coefficient of Variation 26.9
Ctrough of Total Antibody Cycle 5	509 ng/mL Geometric Coefficient of Variation 31.8	658 ng/mL Geometric Coefficient of Variation 40.2

SECONDARY outcome

Timeframe: 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)

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

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.

Outcome measures

Outcome measures
Measure	Cohort A: Loncastuximab Tesirine + Rituximab (Lonca-R) n=17 Participants 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.	Cohort B: Loncastuximab Tesirine + Rituximab (Lonca-R) n=24 Participants 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.
Number of Participants With Confirmed Positive Anti-Drug Antibody (ADA) Response	0 Participants	0 Participants

SECONDARY outcome

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

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Cohort A: Loncastuximab Tesirine + Rituximab (Lonca-R) n=10 Participants 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.	Cohort B: Loncastuximab Tesirine + Rituximab (Lonca-R) n=12 Participants 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.
Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Subscale and Composite Scores Physical Well-being Subscale	-5.70 score on a scale Standard Deviation 4.811	-1.55 score on a scale Standard Deviation 4.793
Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Subscale and Composite Scores Social/family Well-being Subscale	0.52 score on a scale Standard Deviation 1.895	1.22 score on a scale Standard Deviation 5.675
Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Subscale and Composite Scores Emotional Well-being Subscale	2.10 score on a scale Standard Deviation 4.280	-0.95 score on a scale Standard Deviation 2.396
Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Subscale and Composite Scores Functional Well-being Subscale	-3.63 score on a scale Standard Deviation 3.860	-1.44 score on a scale Standard Deviation 6.675
Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Subscale and Composite Scores Lymphoma Subscale	-4.29 score on a scale Standard Deviation 10.577	-0.08 score on a scale Standard Deviation 8.385
Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Subscale and Composite Scores FACT-Lymphoma Trial Outcome Index	-11.99 score on a scale Standard Deviation 16.188	-3.08 score on a scale Standard Deviation 12.452
Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Subscale and Composite Scores FACT-G	-6.71 score on a scale Standard Deviation 11.889	-2.72 score on a scale Standard Deviation 10.649
Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Subscale and Composite Scores FACT-Lymphoma	-8.71 score on a scale Standard Deviation 18.267	-2.81 score on a scale Standard Deviation 14.953

Adverse Events

Cohort A: Loncastuximab Tesirine + Rituximab (Lonca-R)

Serious events: 13 serious events

Other events: 17 other events

Deaths: 5 deaths

Cohort B: Loncastuximab Tesirine + Rituximab (Lonca-R)

Serious events: 16 serious events

Other events: 22 other events

Deaths: 10 deaths

Serious adverse events

Other adverse events

Additional Information

Contact ADC Therapeutics

ADC Therapeutics

Phone: 954-903-7994

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Cohort A: Loncastuximab Tesirine + Rituximab (Lonca-R) n=17 participants at risk 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.	Cohort B: Loncastuximab Tesirine + Rituximab (Lonca-R) n=24 participants at risk 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.
Blood and lymphatic system disorders Anaemia	0.00% 0/17 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	4.2% 1/24 • Number of events 1 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
Cardiac disorders Pericardial effusion	11.8% 2/17 • Number of events 2 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	4.2% 1/24 • Number of events 1 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
Cardiac disorders Atrial fibrillation	5.9% 1/17 • Number of events 1 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	4.2% 1/24 • Number of events 1 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
Cardiac disorders Cardiac failure	11.8% 2/17 • Number of events 2 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	0.00% 0/24 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
Cardiac disorders Cardiac failure congestive	5.9% 1/17 • Number of events 1 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	4.2% 1/24 • Number of events 1 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
Cardiac disorders Cardiogenic shock	5.9% 1/17 • Number of events 1 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	0.00% 0/24 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal pain	5.9% 1/17 • Number of events 1 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	0.00% 0/24 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
Gastrointestinal disorders Ascites	0.00% 0/17 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	4.2% 1/24 • Number of events 1 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
Gastrointestinal disorders Dysphagia	0.00% 0/17 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	4.2% 1/24 • Number of events 1 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
Gastrointestinal disorders Vomiting	5.9% 1/17 • Number of events 1 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	0.00% 0/24 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
General disorders Death	0.00% 0/17 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	4.2% 1/24 • Number of events 1 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
General disorders Oedema peripheral	5.9% 1/17 • Number of events 1 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	0.00% 0/24 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia	5.9% 1/17 • Number of events 1 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	20.8% 5/24 • Number of events 5 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
Infections and infestations Sepsis	11.8% 2/17 • Number of events 3 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	8.3% 2/24 • Number of events 2 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
Infections and infestations COVID-19	5.9% 1/17 • Number of events 1 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	0.00% 0/24 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
Infections and infestations COVID-19 pneumonia	0.00% 0/17 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	4.2% 1/24 • Number of events 1 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
Infections and infestations Influenza	5.9% 1/17 • Number of events 1 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	0.00% 0/24 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
Infections and infestations Septic shock	0.00% 0/17 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	4.2% 1/24 • Number of events 1 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
Nervous system disorders Parkinson's disease	0.00% 0/17 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	4.2% 1/24 • Number of events 1 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
Renal and urinary disorders Acute kidney injury	0.00% 0/17 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	8.3% 2/24 • Number of events 2 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
Renal and urinary disorders Hydronephrosis	0.00% 0/17 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	4.2% 1/24 • Number of events 1 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pleural effusion	29.4% 5/17 • Number of events 5 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	8.3% 2/24 • Number of events 2 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	11.8% 2/17 • Number of events 2 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	8.3% 2/24 • Number of events 2 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.9% 1/17 • Number of events 1 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	4.2% 1/24 • Number of events 1 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory failure	5.9% 1/17 • Number of events 1 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	4.2% 1/24 • Number of events 1 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/17 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	4.2% 1/24 • Number of events 1 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/17 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	4.2% 1/24 • Number of events 3 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	5.9% 1/17 • Number of events 1 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	0.00% 0/24 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	5.9% 1/17 • Number of events 1 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	0.00% 0/24 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/17 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	4.2% 1/24 • Number of events 1 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/17 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	4.2% 1/24 • Number of events 1 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.
Vascular disorders Embolism	0.00% 0/17 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.	8.3% 2/24 • Number of events 2 • All cause mortality: up to a maximum of 17.1 months; serious and other adverse events: up to approximately 8 months All-Treated Population: All participants who received at least 1 dose of study drug.